Belongs to the SRP receptor beta subunit family.
Belongs to the thymidylate kinase family.
Catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), the immediate precursor for the DNA building block dTTP (PubMed:18477629, PubMed:19126267, PubMed:31934749, PubMed:20353400). Can also phosphorylate dGMP and to a lesser extent GMP, dUMP and dIMP (PubMed:18477629, PubMed:19126267, PubMed:31934749, PubMed:20353400). Can use either ATP or dATP as phosphate donors in presence of Mg(2+) (PubMed:18477629).
Homodimer (PubMed:18477629, PubMed:19126267, PubMed:31934749). Binds two dTMP molecules per dimer (PubMed:31934749). Binds only one dTGP molecule per dimer (PubMed:31934749).
Inhibited by deoxyguanosine (dG), deoxythymidine (dT) and azidothymidine (AZT).
Phosphorylates AZT monophosphate (AZT-MP) more efficiently than human DTYMK/TMPK. The conversion of AZT MP into AZT diphosphate (AZT-DP) by the human enzyme is a crucial step in the production of the active anti-HIV drug AZT triphosphate (AZT-TP).
Possible candidate for an effective malaria vaccine as determined by epitope response in sera.
Belongs to the snRNP Sm proteins family.
Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
Expressed throughout intraerythrocytic life cycle, the level increases significantly from the ring to the early trophozoite stage and remains relatively constant through the late schizont stage (at protein level) (PubMed:11682491). The amount of protein does not coincide with the transcript levels, which are maximal in early trophozoites and subsequently down-regulated in late stage trophozoites and schizonts (PubMed:10744765).
GSK4 (5-methyl-N-[2-(2-oxo-1-azepanyl)ethyl]-2-phenyl-1,3-oxazole-4-carbox-amide) disrupts the transport activity at 500 nM (PubMed:36977719). Inhibited partially by 10 uM dipyridamole (PubMed:10744765).
Parasites are not viable if adenosine, inosine, guanine, guanosine, xanthine or hypoxanthine are present at concentrations below 50 uM and require higher concentrations of hypoxanthine, adenosine or inosine to progress beyond the ring stage of development.
Sodium-independent nucleoside and nucleobase transporter with a broad substrate specificity (PubMed:36977719, PubMed:10744765, PubMed:10861212, PubMed:18639591, PubMed:16751273). Plays a key role in the utilization of host purine sources by P.falciparum during intraerythrocytic development enabling parasite growth in the presence of physiological concentrations of adenosine, inosine, guanine, guanosine, xanthine and hypoxanthine (PubMed:18639591, PubMed:16751273). Essential for parasite transition from ring to trophozoite or from trophozoite to schizont stage but not for erythrocyte invasion by merozoites (PubMed:16751273).
With an efficiency similar to that for uridine, can mediate the cellular uptake of nucleoside analogs used in cancer chemotherapy: fludarabine (9-beta-D-arabinosyl-2-fluoroadenine), cladribine (2-chloro-2'-deoxyadenosine) and gemcitabine (2',2'-difluoro-2'-deoxycytidine) (PubMed:10861212). Unlike the mammalian transporters, can efficiently transport the anti-viral nucleoside analogs: AZT (3'-azido-3'-deoxythymidine), ddC (2',3'-dideoxycytidine) and ddI (2',3'-dideoxyinosine) (PubMed:10861212). In contrast to the human transporter SLC29A1, has low sensitivity to the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) (PubMed:10744765).
Belongs to the ribonucleoside diphosphate reductase large chain family.
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Belongs to the eukaryotic release factor 1 family. Pelota subfamily.
Component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway. In the Pelota-HBS1L complex, pelo recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May also function as a storage protein or ligandin for parasitotoxic ferriprotoporphyrin IX (hemin).
Homodimer. In the absence of ligands two homodimers may interact to form a tetramer.
Inhibited by chloroquine, cibacron blue, ferriprotoporphyrin IX (hemin) and S-hexylglutathione.
Belongs to the histone deacetylase family. HD Type 1 subfamily.
Belongs to the histidine acid phosphatase family. VIP1 subfamily.
Belongs to the bacterial ribosomal protein bL27 family.
The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.
Belongs to the protein prenyltransferase subunit beta family.
Belongs to the cyclophilin-type PPIase family.
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Belongs to the universal ribosomal protein uL3 family.
One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
Catalyzes the transfer of electrons from NADPH to thioredoxins TRX1, TRX2 and TRX3, which in turn act as reductants of disulfide containing proteins (PubMed:9368022, PubMed:11013257, PubMed:16910770, PubMed:23845423). Able to reduce nitroglutathione (GSNO), a compound involved in the transport of nitric oxide (NO); however, TRX1 is more efficient in reducing GSNO (PubMed:11013257). Has no catalytic activity towards oxidized glutathione (GSSG) (PubMed:11013257).
In Plasmodium, the C-terminal redox center, which acts as the active site, is formed by two cysteines while in mammalian TRXR this redox center is composed of a cysteine-selenocysteine active site.
Produced by alternative initiation at Met-77 of isoform 1.
Belongs to the methyltransferase superfamily. Fibrillarin family.
Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.
Belongs to the universal ribosomal protein uL4 family.
Belongs to the TtcA family. CTU1/NCS6/ATPBD3 subfamily.
Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). Directly binds tRNAs and probably acts by catalyzing adenylation of tRNAs, an intermediate required for 2-thiolation. It is unclear whether it acts as a sulfurtransferase that transfers sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position.
Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family.
Lacks conserved residue(s) required for the propagation of feature annotation.
Belongs to the folylpolyglutamate synthase family.
Belongs to the TRAPP small subunits family. BET3 subfamily.
May play a role in vesicular transport from endoplasmic reticulum to Golgi.
Non-catalytic component of the proteasome.
During the asexual blood stage, recruits host complement factor H CFH to the surface of merozoites resulting in the down-regulation of the host complement alternative pathway and thus, protecting merozoites from complement-mediated lysis.
Expressed during the parasite blood stage, specifically in schizonts (at protein level).
In strain D10, causes a loss of binding of human CFH to the merozoite surface resulting in a 7-fold increase in host complement-mediated merozoite lysis.
Interacts with host complement factor CFH isoform 1 (via sushi 4-6 domains) and CFH isoform FHL-1 (via sushi 4-6 domains); this interaction recruits CFH onto the merozoite surface preventing complement-mediated cell lysis (PubMed:26700768). The interaction does not affect CFH activity (PubMed:26700768).
Belongs to the adaptor complexes small subunit family.
Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.
The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex.
Belongs to the bacterial ribosomal protein bL9 family.
Belongs to the RNase HII family. Eukaryotic subfamily.
Endonuclease that specifically degrades the RNA of RNA-DNA hybrids.
Manganese or magnesium. Binds 1 divalent metal ion per monomer in the absence of substrate. May bind a second metal ion after substrate binding.
Belongs to the TRAPP small subunits family.
Part of the multisubunit transport protein particle (TRAPP) complex.
Belongs to the universal ribosomal protein uS9 family.
Belongs to the protein kinase superfamily. ADCK protein kinase family.
Expressed during the asexual cell-cycle on the cell surface of the host erythrocytes.
LSm subunits form a heteromer with a doughnut shape.
Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA.
Belongs to the phosphatidylserine decarboxylase family. PSD-B subfamily. Eukaryotic type I sub-subfamily.
Binds 1 pyruvoyl group covalently per subunit.
Catalyzes the formation of phosphatidylethanolamine (PtdEtn) from phosphatidylserine (PtdSer). Plays a central role in phospholipid metabolism and in the interorganelle trafficking of phosphatidylserine.
Heterodimer of a large membrane-associated beta subunit and a small pyruvoyl-containing alpha subunit.
Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The autoendoproteolytic cleavage occurs by a canonical serine protease mechanism, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl prosthetic group on the alpha chain. During this reaction, the Ser that is part of the protease active site of the proenzyme becomes the pyruvoyl prosthetic group, which constitutes an essential element of the active site of the mature decarboxylase.
Belongs to the universal ribosomal protein uS11 family.
Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space.
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space.
Belongs to the bacterial ribosomal protein bL19 family.
Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.
Belongs to the protein kinase superfamily.
Belongs to the thiolase-like superfamily. FabH family.
Belongs to the eIF-2B alpha/beta/delta subunits family.
Belongs to the bacterial ribosomal protein bL12 family.
Belongs to the DEAD box helicase family.
The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.
Belongs to the cyclic nucleotide phosphodiesterase family.
Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
Expressed during the asexual blood stage, with highest levels in the late schizont stage.
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP (PubMed:30794532). Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively (PubMed:30794532). By regulating cAMP levels during the asexual blood stage and, thus PKA activation, required for merozoite invasion of erythrocytes and for the parasite development immediately following invasion (PubMed:30794532).
Activated by calcium (Probable). Upon calcium binding to the EF-hand domain 2, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (Probable). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-279, which leads to the kinase activation (By similarity).
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDPK subfamily.
Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (By similarity). In the mosquito midgut, regulates the gliding motility of the ookinete which is essential for the ookinete to invade the midgut epithelium (By similarity). However, another study showed that while required for ookinete invasion of the midgut epithelium, is not required for ookinete gliding motility (By similarity).
Expressed in sexual stages, but not in asexual stages.
The EF-hand domain 1 cannot bind calcium due to the presence of a Lys instead of an Asp at position 435 and a Gln instead of a Glu at position 442 preventing calcium binding (PubMed:28746405, PubMed:21287613). The EF-hand domains 3 and 4 probably bind calcium constitutively when calcium levels are low, while the EF-hand domain 2 binds calcium following an increase in calcium levels (PubMed:21287613).
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive. The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains.
Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.
Mediates the uptake of pyruvate into mitochondria.
Belongs to the FAD-dependent glycerol-3-phosphate dehydrogenase family.
Belongs to the glutamate synthase family.
Belongs to the ATP-dependent AMP-binding enzyme family.
Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.
Binds 1 divalent metal cation per subunit.
In the mevalonate-independent isoprenoid biosynthetic pathway, converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate into 2C-methyl-D-erythritol 2,4-cyclodiphosphate and CMP.
Belongs to the acetyltransferase family. GCN5 subfamily.
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Catalyzes the exchange of ADP and ATP across the membrane.
Belongs to the universal ribosomal protein uL22 family.
Belongs to the eukaryotic-type primase large subunit family.
DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication.
Belongs to the WD repeat CDC20/Fizzy family.
Belongs to the small heat shock protein (HSP20) family.
Expressed during all parasite blood stages (at protein level).
Has peptidylprolyl isomerase (PPIase) and co-chaperone activities (PubMed:15664653, PubMed:15850699). Assists protein folding by catalyzing the peptidyl conversion of cis and trans rotamers of the prolyl amide bond of protein substrates (PubMed:15664653, PubMed:15850699, PubMed:23974147). Inhibits calcineurin phosphatase activity in vitro (PubMed:15850699, PubMed:17289400, PubMed:23974147). Plays an essential role in merozoite egress from host erythrocytes (PubMed:15664653, PubMed:23974147).
Homodimer (PubMed:17289400). Interacts (via TPR repeats) with HSP90 (probably via MEEVD motif) (PubMed:15850699, PubMed:19691130).
Inhibited by FK506 and its derivates, such as ascomycin, and rapamycin (PubMed:15664653, PubMed:15850699). FK506 and rapamycin inhibit peptidylprolyl isomerase activity but not chaperone activity (PubMed:15664653). Inhibited by N-(2-ethyl-phenyl)-2-(3H-imidazao [4, 5-b] pyridin-2-yl-sulfanyl)-acetamide (D44) (PubMed:23974147). Not inhibited by cyclosporin A (PubMed:15664653, PubMed:15850699). Inhibition of calcineurin phosphatase activity is enhanced by FK506 (PubMed:15850699).
The PPIase FKBP-type domain contributes to the chaperone activity (PubMed:15664653). Required for the inhibition of calcineurin phosphatase activity (PubMed:15850699).
The TPR repeats are important for the chaperone activity (PubMed:15664653). In another study, these repeats appear to be dispensable for chaperone activity (PubMed:15850699). Dispensable for PPIase activity (PubMed:15850699). Dispensable for the inhibition of calcineurin phosphatase activity (PubMed:15850699).
Involved in cytoplasm to vacuole transport (Cvt), pexophagy, mitophagy and nucleophagy. Works as scaffold proteins that recruit ATG proteins to the pre-autophagosome (PAS), the site of vesicle/autophagosome formation.
Belongs to the nucleosome assembly protein (NAP) family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.
Specifically methylates the N1 position of guanosine-37 in various cytoplasmic and mitochondrial tRNAs. Methylation is not dependent on the nature of the nucleoside 5' of the target nucleoside. This is the first step in the biosynthesis of wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and required for accurate decoding.
Plays a role in vesicular protein sorting.
The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.
Belongs to the sphingomyelin synthase family.
Belongs to the eukaryotic ribosomal protein eS26 family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.
Belongs to the helicase family. RecQ subfamily.
Cleaved into a 45kDa form during merozoite invasion of host erythrocyte.
Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:25583518, PubMed:27374406, PubMed:25296023, PubMed:22080952, PubMed:18827878, PubMed:19000690, PubMed:31204103, PubMed:28186186, PubMed:28409866). By binding P113 at the surface of the merozoite and human BSG/basigin on the erythrocyte membrane, leads to the establishment of a tight junction between the merozoite and host erythrocyte membranes (PubMed:25583518, PubMed:27374406, PubMed:25296023, PubMed:22080952, PubMed:28186186). In addition, the interaction with BSG results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:27374406, PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866).
Expressed during parasite asexual blood stages, specifically at the schizont stage and in free merozoites (at protein level).
Forms a complex composed of RH5, P113 and human BSG/basigin; the complex bridges the merozoite and host erythrocyte membranes (PubMed:28186186). Within the complex, interacts (via C-terminus) with human BSG/basigin isoform 2 (via the extracellular domain); the interaction is independent of BSG glycosylation status (PubMed:22080952, PubMed:25296023, PubMed:28186186, PubMed:24297912, PubMed:30542156, PubMed:28096331). Weakly interacts with P.troglodytes BSG but not with G.gorilla BSG (PubMed:24297912). Also, interacts (via N-terminus) with P113; the interaction tethers RH5 to the merozoite membrane (PubMed:28186186). Component of the PfRH5 adhesion complex composed of 1 copy of CyRPA, RH5 and RIPR; the complex is formed during merozoite invasion of host erythrocytes specifically at the interface between the parasite and host membranes (PubMed:25583518, PubMed:27374406, PubMed:28186186, PubMed:21909261, PubMed:30542156). Within the complex, interacts with CyRPA (PubMed:28186186, PubMed:30542156). CyRPA recruits RIPR to the RH5-P113-BSG complex; the formation of the PfRH5 adhesion complex increases the affinity of RH5 for BSG and probably leads to the release of RH5 from P113 while maintaining the interaction of the PfRH5 adhesion complex with BSG (PubMed:28186186, PubMed:30542156).
Potential candidate for the development of parasite blood stage vaccines. In vitro and in vivo, induces neutralizing antibodies capable of inhibiting merozoite invasion of host erythrocytes.
Belongs to the methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.
Belongs to the V-ATPase proteolipid subunit family.
Alternates between an inactive GDP-bound form and an active GTP-bound form (PubMed:32144363). Intrinsic GTPase activity is almost undetectable in vitro (By similarity). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by GTPase-activating protein ARFGAP1 (PubMed:32144363).
Belongs to the small GTPase superfamily. Arf family.
Small GTPase involved in protein trafficking between different compartments (PubMed:21045287). Modulates vesicle budding and uncoating within the Golgi complex (By similarity). In its GTP-bound form, triggers the recruitment of coatomer proteins to the Golgi membrane (By similarity). The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles (By similarity). Regulates the transport of N-acylated AK2 to the parasitophorous vacuole membrane (PubMed:33604307). May be involved in the activation of lipid kinase PIP5K (PubMed:19171150).
Ubiquitin-protein ligase which is mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome.
Belongs to the type II topoisomerase GyrA/ParC subunit family.
Belongs to the activator 1 large subunit family.
Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.
Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.
Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs.
Belongs to the eukaryotic ribosomal protein eL8 family.
Belongs to the DHHC palmitoyltransferase family.
The DHHC domain is required for palmitoyltransferase activity.
Transcription elongation factor implicated in the maintenance of proper chromatin structure in actively transcribed regions.
Belongs to the class-I aminoacyl-tRNA synthetase family.
Belongs to the heat shock protein 70 family.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP. The complex of SRP9 and SRP14 is required for SRP RNA binding.
Heterodimer with SRP9; binds RNA as heterodimer. Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9.
Belongs to the clathrin light chain family.
Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
Belongs to the glutaminase PdxT/SNO family.
Catalyzes the hydrolysis of glutamine to glutamate and ammonia as part of the biosynthesis of pyridoxal 5'-phosphate. The resulting ammonia molecule is channeled to the active site of Pdx1.
Expressed throughout development. Highest expression in segmenters stage followed by schizonts stage.
In the presence of Pdx1, forms a dodecamer of heterodimers. Only shows activity in the heterodimer.
The active site is a redox-active disulfide bond.
Belongs to the universal ribosomal protein uL10 family.
Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
Component of the ribosomal small subunit (SSU) processome.
Required for 40S ribosome biogenesis. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.
Belongs to the V-ATPase V0D/AC39 subunit family.
Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex.
Belongs to the proteasome subunit S3 family.
Belongs to the protein kinase superfamily. BUD32 family.
Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.
Belongs to the heat shock protein 90 family.
Belongs to the peptidase M24A family. Methionine aminopeptidase eukaryotic type 2 subfamily.
Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity.
Belongs to the MIP/aquaporin (TC 1.A.8) family.
Belongs to the methyltransferase superfamily. LCMT family.
Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues.
Expressed during the parasite blood stage, including in rings, trophozoites and schizonts (at protein level) (PubMed:14698441). Expression increases in trophozoites and schizonts (PubMed:14698441).
Interacts with dual specificity protein phosphatase YVH1.
Required for maturation of ribosomal RNAs and formation of the large ribosomal subunit.
Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
Belongs to the DNA polymerase epsilon subunit B family.
Catalyzes the reversible transfer of the terminal phosphate group between GTP and AMP (PubMed:15478799). Has very low activity with UTP, ITP, CTP and IMP and no activity with ATP, GMP, CMP and UMP in vitro (PubMed:15478799).
Inhibited by the dinucleoside pentaphosphate compound P1,P5-di(guanosine-5') pentaphosphate (GP5A).
There is a putative zinc finger domain which may bind to iron.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
Small GTPase required for proper localization of RNA polymerase II and III (RNAPII and RNAPIII). May act at an RNAP assembly step prior to nuclear import.
Belongs to the ubiquitin-activating E1 family.
Belongs to the RNA cytidine acetyltransferase family. NAT10 subfamily.
RNA cytidine acetyltransferase with specificity toward both 18S rRNA and tRNAs. Catalyzes the formation of N(4)-acetylcytidine (ac4C) in 18S rRNA. Required for early nucleolar cleavages of precursor rRNA at sites A0, A1 and A2 during 18S rRNA synthesis. Catalyzes the formation of ac4C in serine and leucine tRNAs. Requires a tRNA-binding adapter protein for full tRNA acetyltransferase activity but not for 18S rRNA acetylation.
Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.
In the N-terminal section; belongs to the ubiquitin family.
Belongs to the bacterial ribosomal protein bL17 family.
Belongs to the adaptor complexes large subunit family.
Component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.
Belongs to the iron/manganese superoxide dismutase family.
Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.
As part of the purine salvage pathway, catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (PubMed:18957439, PubMed:14982926, PubMed:16131758, PubMed:19575810, PubMed:24416224, PubMed:29440412). Preferentially acts on inosine and guanosine, and to a lesser extent on 2'-deoxyguanosine and guanosine (PubMed:14982926, PubMed:16131758, PubMed:19575810). Also catalyzes the phosphorylation of S-methyl-5'-thioinosine (MTI) to hypoxanthine; MTI is produced by adenosine deaminase (ADA)-mediated breakdown of S-methyl-5'-thioadenosine (MTA), a major by-product of polyamine biosynthesis (PubMed:18957439, PubMed:14982926, PubMed:24416224). Generates hypoxanthine from both the purine salvage pathway and from polyamine metabolism which is required for nucleic acids synthesis (PubMed:18957439, PubMed:14982926, PubMed:24416224). Has no activity towards adenosine (By similarity).
Belongs to the PNP/MTAP phosphorylase family.
Expressed during the parasite blood stage, including in trophozoites (at protein level).
Inhibited by Immucillin-H and 5'-methylthio-Immucillin-H (PubMed:14982926, PubMed:24416224). Inhibited by 5'-deaza-1'-aza-2c-deoxy-1'-(9-methylene)-Immucilin-G (DADMe-ImmG) (PubMed:29440412).
Severe growth defect in host erythrocytes which is rescued by the addition of exogenous purines (PubMed:18957439). Loss of purine nucleoside phosphorylase activity (PubMed:18957439).
Expressed during the parasite blood stage, in schizonts (at protein level).
The Asn-rich domain is dispensable for deubiquitinating and deneddylating activities.
Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8.
Belongs to the major facilitator superfamily. Folate-biopterin transporter (TC 2.A.71) family.
Belongs to the dynein light chain family.
Belongs to the phosphatidylethanolamine-binding protein family.
Belongs to the universal ribosomal protein uL24 family.
One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.
Involved in the early part of the secretory pathway.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex.
The RNA gate region regulates mRNA cap recognition to prevent promiscuous mRNA-binding before assembly of eif3d into the full eukaryotic translation initiation factor 3 (eIF-3) complex.
mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation. In the eIF-3 complex, eif3d specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs.
Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase NEP1 family.
Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.
Catalytic subunit of the dimeric E1 enzyme, which activates NEDD8.
Heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter.
Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. Known to play a role, in vitro, in the folding of actin and tubulin (By similarity).
Belongs to the universal ribosomal protein uS14 family.
Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation.
Component of the glideosome complex composed of GAP50, GAP45, MTIP and MyoA; the complex is formed during the late schizont stage and in merozoites (PubMed:16321976, PubMed:19576251, PubMed:22479457). MyoA, MTIP and GAP45 probably form an initial complex in the cytoplasm which is then recruited to the outer face of the inner membrane complex via the interaction with GAP50 (PubMed:16750579). Interacts with GAP50; the interaction is independent of GAP45 phosphorylation status and can also occur independently of the formation of the glideosome complex (PubMed:19576251).
Component of the glideosome complex, an inner membrane complex structure involved in parasite gliding motility and host cell invasion (PubMed:16321976, PubMed:16750579, PubMed:19576251, PubMed:22479457). During the asexual blood stage, required in schizonts to recruit MTIP and MyoA to the inner membrane complex where they assemble with GAP50 to form the glideosome complex (PubMed:19576251, PubMed:29970464). By regulating the formation of the glideosome, plays an essential role during merozoite invasion of host erythrocytes (PubMed:29970464).
Expressed during the asexual blood stage; expression begins in trophozoites and peaks in schizonts and merozoites (at protein level).
N-myristoylated by NMT (PubMed:16750579). N-myristoylation may contribute to the targeting of GAP45 to the inner membrane complex with the subsequent palmitoylation strengthening the interaction with the membrane (Probable).
Palmitoylated (PubMed:16750579). Palmitoylation appears to follow N-myristoylation and may strengthen the interaction with the inner membrane complex (Probable).
Phosphorylated at multiple sites (PubMed:18768477, PubMed:19576251). Phosphorylation increases during the schizont stage and peaks in segmented merozoites (PubMed:18768477). May be phosphorylated by PKB (PubMed:18165240). In schizonts, phosphorylated at Ser-89 and Ser-149 in response to phospholipase C-mediated calcium release (PubMed:22558243). Phosphorylation at Ser-149 begins in early schizonts while phosphorylation at Ser-103 begins in late schizonts (PubMed:22558243). Phosphorylation at Ser-89, Ser-103 and Ser-149 appears to be dispensable for GAP45 inner membrane complex localization or GAP45 inclusion in the glideosome complex (PubMed:22479457, PubMed:22558243). Phosphorylation is not required for interaction with GAP50; however, it may regulate the interaction with MTIP and MyoA (PubMed:19576251).
Schizonts develop at the same rate as wild type parasites and are morphologically normal at the end of cycle 0 (PubMed:29970464). However, proliferation is impaired during the subsequent cycle (PubMed:29970464). Expression levels of MyoA and MTIP are severely reduced (PubMed:29970464). Expression levels and subcellular location of GAP50 is not affected (PubMed:29970464). No visible defects in intracellular membrane complex development or morphology in the intracellular merozoites (PubMed:29970464). No defect in parasite egress from host erythrocytes (PubMed:29970464). Impaired invasion of host erythrocytes; merozoites bind to erythrocytes but do not induce surface deformation of the erythrocyte and fail to form rings (PubMed:29970464). Microneme discharge is normal (PubMed:29970464).
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.
Localizes to the merozoite surface. Mostly concentrated in secretory organelles at the apical end of the parasite, exclusively at an early stage of schizont development. Probably localizes in the rhoptry organelles.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.
This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.
Belongs to the protease inhibitor I71 family.
Cysteine protease inhibitor (PubMed:17083274, PubMed:24699522). Inhibits cysteine protease falcipains FP2 and FP3 (PubMed:17083274). Required for the invasion of host erythrocytes by merozoites (PubMed:17083274). In the mosquito vector, essential for the gliding motility of hemocoel sporozoites and, therefore, for salivary gland invasion and the subsequent transmission from the mosquito to the mammalian host (By similarity). Required for the invasion of host hepatocytes (By similarity). During the liver stage, may prevent host hepatocyte cell death likely by inhibiting host cysteine proteases (By similarity).
Expressed during the asexual blood stage; highly expressed in early rings, late schizonts and free merozoites, and to a lesser extent in late rings and early schizonts (at protein level) (PubMed:17083274, PubMed:23421981). Not expressed trophozoites (at protein level) (PubMed:17083274). Expressed during the liver stage (at protein level) (PubMed:23421981).
Oligomer; probably composed of 10 monomers.
The C-terminal domain is sufficient for cysteine protease inhibition.
Belongs to the archaeal Rpo10/eukaryotic RPB10 RNA polymerase subunit family.
Belongs to the universal ribosomal protein uL6 family.
Belongs to the actin-binding proteins ADF family.
Interacts with monomeric actin, does not bind to actin polymers.
Not involved in actin polymerisation, instead functions to stimulate nucleotide exchange on monomeric actin and influence turnover of the small amount of cytosolic actin microfilaments. Essential for erythrocytic schizogony (By similarity).
Belongs to the ribose-phosphate pyrophosphokinase family.
Exhibits a high rate of non-synonymous polymorphism is different strains, suggesting that it adapts to different Anopheles vector species.
Expressed only in female gametocytes following emergence from red blood cells.
Mediates evasion of the mosquito innate immune response by suppressing midgut nitration responses that are critical to activate the mosquito complement system. It is unclear whether the protein has a role in passive evasion by making the parasite invisible to the mosquito immune system, acts as a decoy to prevent recognition of another surface protein or anchors the decoy protein. Not required for female fertility.
Reduced parasite survival in the mosquito. Parasites produce normal numbers of oocysts when included in the blood meal of the mosquito vector.
Belongs to the eukaryotic ribosomal protein eL15 family.
Belongs to the eukaryotic ribosomal protein eS7 family.
Catalyzes the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Acts in the terminal step of the DOXP/MEP pathway for isoprenoid precursor biosynthesis.
Was shown to bind 1 [3Fe-4S] cluster (PubMed:24188825). However, it initially contains a [4Fe-4S] cluster which easily degrades into a [3Fe-4S] form in the presence of oxygen (Probable).
Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus.
Component of the hemozoin formation complex (HFC) composed of falcipain 2, plasmepsins PMII, PMIII/HAP and PMIV, heme detoxifying protein HDP and falcilysin FLN (PubMed:23471987). The HFC complex is involved in hemoglobin degradation and detoxification of heme in the food vacuole during the asexual blood stage (PubMed:23471987).
During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:29943906). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (By similarity). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).
Expressed during the asexual blood stage including in trophozoites (at protein level).
Inhibited by pepstatin A (PubMed:29943906). Inhibited by KNI derived compounds (KNI-10742, 10743, 10395, 10333, and 10343) (PubMed:29943906).
Proteolytically cleaved into the soluble active mature form in the digestive vacuole by cysteine protease falcipains; the process begins at the early ring stage (PubMed:14709539, PubMed:18308731). Proteolysis requires an acidic environment (PubMed:14709539, PubMed:18308731). In absence of falcipains, autoprocessing may serve as an alternate activation system (PubMed:18308731).
Slight decrease in proliferation and slight increase in doubling time during the asexual blood stage.
Belongs to the eukaryotic ribosomal protein eS10 family.
Belongs to the methyltransferase TRM13 family.
tRNA methylase which 2'-O-methylates cytidine(4) in tRNA(Pro) and tRNA(Gly)(GCC), and adenosine(4) in tRNA(His).
Belongs to the ubiquitin-conjugating enzyme family.
Activated by calcium (PubMed:29716996, PubMed:18768477, PubMed:23204525, PubMed:17123645, PubMed:32484216). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (Probable) (PubMed:23204525). This, in turn may facilitate the autophosphorylation of the activation loop at Thr-231, which leads to the kinase activation (PubMed:19307175). May be negatively regulated by PKA-mediated phosphorylation (PubMed:28680058). Inhibited by purfalcamine (PubMed:23204525, PubMed:29716996).
Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (PubMed:18768477, PubMed:19307175, PubMed:28680058, PubMed:29716996). By phosphorylating various proteins, required for microneme secretion and thus merozoite egress from and invasion of host erythrocytes (PubMed:23204525, PubMed:28680058, PubMed:29716996). During gametogenesis, essential for the development of both male and female gametes (By similarity). Phosphorylates SERA5 p50 which enhances SERA5 p50 protease activity; however, SERA5 p50 protease activity has been shown in other studies to be controversial (PubMed:29716996). Probably by phosphorylating SERA5 p50, plays a role in merozoite egress from host erythrocytes (PubMed:29716996). Probably prior or during merozoite invasion of host erythrocytes, phosphorylates rhoptry protein RhopH3 which is required for RhopH3 localization to rhoptries and for its secretion (PubMed:33024030). Probably in late schizonts, phosphorylates myosin A tail domain-interacting protein MTIP and glideosome-associated protein 45 GAP45, both of which are components of the motor complex that generates the force required by the parasite to invade host cells (PubMed:18768477, PubMed:28680058, PubMed:22539638). In late schizonts, phosphorylates inner membrane complex protein IMC1g (PubMed:28680058). In late schizonts, phosphorylates PKA regulatory subunit PKAr in a calcium-dependent manner, which may contribute to the dissociation of regulatory PKAr and catalytic PKAc subunits and promote the activation of PKAc (PubMed:28680058). May phosphorylate raf kinase inhibitory protein RKIP which in turn may regulate CDPK1 catalytic activity (PubMed:17123645). May phosphorylate proteins of the host erythrocyte membranes (By similarity).
Conditional knockdown at the ring stage produces the development of mature schizonts and the subsequent release of merozoites from the host erythrocytes; however, the invasion of new erythrocytes by these merozoites is severely reduced due to a severe defect in adhesion to the erythrocyte membrane (PubMed:28680058). In merozoites, release of host glycophorin A/GYPA ligand EBA-175 from micronemes is impaired but not AMA1 (PubMed:28680058). In late schizont, phosphorylation of several proteins including GAP45, IMC1g and PKAr is reduced (PubMed:28680058). Reduced PKA activity (PubMed:28680058). Rhoptry protein RhopH3 phosphorylation and secretion are reduced in merozoites (PubMed:33024030).
Expressed during parasite asexual blood stages, specifically at the ring and schizont stages, in free merozoites and to a lesser extent in trophozoites (at protein level).
Monomer (PubMed:26149123). Forms a high molecular weight (250 and 400 kDa) complex (PubMed:26149123). Forms a complex composed of CDPK1, PKA regulatory subunit PKAr and 14-3-3I; the complex is formed in merozoites in response to low extracellular level of K(+) and may play a role in microneme secretion (PubMed:32817103). Interacts (when phosphorylated) with 14-3-3I in a Ca(2+)-independent manner; the interaction does not regulate CDPK1 catalytic activity but is required for merozoite invasion of host erythrocytes (PubMed:32484216, PubMed:32817103). Interacts with PKA regulatory subunit PKAr; in a Ca(2+)-dependent manner (PubMed:28680058, PubMed:32817103). Interacts with SERA5 p50 in the late schizont stage (PubMed:29716996). Interacts with inner membrane complex protein IMC1g in late schizonts (PubMed:28680058). Interacts with rhoptry protein RhopH3 in merozoites (PubMed:33024030).
Myristoylated (PubMed:15491359). Myristoylation, palmitoylation and the basic cluster motif are required for the localization to the parasitophorous vacuole membrane (PubMed:15491359).
Palmitoylated (Probable) (PubMed:32003970). Palmitoylation increases in merozoites in response to low level of extracellular K(+) in the host blood (PubMed:32003970). Myristoylation, palmitoylation and the basic cluster motif are required for the localization to the parasitophorous vacuole membrane (PubMed:15491359).
Phosphorylation at Ser-64 occurs at late schizont stage and regulates CDPK1 protein-protein interaction (PubMed:26149123). Phosphorylated at Ser-28, Ser-34 and Ser-64 in merozoites in response to low extracellular level of K(+) (PubMed:32817103). Phosphorylation at Thr-231 may regulate CDPK1 kinase activity (PubMed:26149123). Phosphorylation increases in response to an increase in intracellular Ca(2+) levels (PubMed:32484216). Autophosphorylated in vitro (PubMed:17123645, PubMed:22539638, PubMed:23204525, PubMed:26149123, PubMed:32484216). Autophosphorylation does not affect membrane localization in vitro (PubMed:15491359).
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (PubMed:19307175). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (PubMed:19307175, PubMed:23204525).
Unlike P.berghei CDPK1, appears to be involved in the asexual blood stage and in male gamete exflagellation prior host erythrocyte membrane rupture.
Belongs to the eukaryotic ribosomal protein eL21 family.
Belongs to the isocitrate and isopropylmalate dehydrogenases family.
Binds 1 Mg(2+) or Mn(2+) ion per subunit.
Belongs to the eukaryotic RPB4 RNA polymerase subunit family.
Belongs to the uroporphyrinogen decarboxylase family.
Displays aminopeptidase activity with a broad substrate specificity (PubMed:9879894, PubMed:12166515, PubMed:21659511, PubMed:22359643, PubMed:34133730, PubMed:33536500, PubMed:19196988, PubMed:21844374, PubMed:23897806). Preferentially, cleaves after Leu and Met, but cleaves also after Ala and Arg (PubMed:12166515, PubMed:22359643, PubMed:33536500, PubMed:21844374). Low activity towards Lys, Phe, Tyr, Trp, Gln, Ser and Gly and negligible activity towards Glu, Asp, Pro, Ile, Thr, Val, His and Asn (PubMed:22359643). Has dipeptidase activity (PubMed:21659511, PubMed:23897806). Plays a role in the terminal stages of host hemoglobin digestion by cleaving the N-terminal residue of small hemoglobin-derived oligopeptides (PubMed:21659511, PubMed:34133730, PubMed:21844374).
Expressed at low levels during the asexual blood stage in trophozoites and early schizonts (at protein level) (PubMed:9879894, PubMed:20591164). No expression at the early ring stage and in mature segmented schizonts (at protein level) (PubMed:20591164).
Expressed during the asexual blood stage in late rings, trophozoites and schizonts (at protein level) (PubMed:9879894, PubMed:12166515, PubMed:17895246, PubMed:20591164, PubMed:33536500, PubMed:19196988). No expression at the early ring stage (at protein level) (PubMed:12166515, PubMed:20591164).
Expressed during the asexual blood stage in mature rings, trophozoites and schizonts (at protein level) (PubMed:9879894, PubMed:12166515, PubMed:20591164, PubMed:21659511). No expression at the early ring stage (at protein level) (PubMed:12166515, PubMed:20591164).
Heterodimer of the p68 form and the p35 form which are derived from the p120 precursor.
Inhibited by 1,10-phenanthroline, EDTA and bestatin (PubMed:12166515, PubMed:21659511, PubMed:34133730, PubMed:19196988). Inhibited by (Benzyl)Tyr-Ala (BTA) (PubMed:21844374). Activity is not affected by phosphoramidin, PMSF, leupeptin, iodoacetamide or pepstatin (PubMed:12166515, PubMed:19196988).
May have an additional translation initiation (PubMed:21659511). Translation initiation at the first Met codon would generate a form that contains the signal peptide, enters the endomembrane system, and ultimately reaches the food vacuole (PubMed:21659511). Initiation of translation at an internal Met codon would result in a form that lacks the signal peptide, thereby re-directing the protein to the cytosol (Probable). A nuclear localization signal would then lead to nuclear import (Probable).
The cytoplasm localization is controversial. One study showed that the protein localizes predominantly to the nucleus and the food vacuole (PubMed:21659511). Two studies showed that it localizes to the cytoplasm and the food vacuole (PubMed:33536500, PubMed:12166515). The discrepancy between studies is due to the staining procedure (PubMed:21659511).
The full length protein appears to be cleaved into a 120 kDa precursor. This precursor is then proteolytically cleaved at the N-terminus generating a 96 kDa form which is further processed at the C-terminus into 68 kDa and 35 kDa forms that remain associated.
Belongs to the PPP phosphatase family. PP-5 (PP-T) subfamily.
Belongs to the RecA family. RAD51 subfamily.
Binds to single and double-stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA.
Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II.
Belongs to the bacterial ribosomal protein bL20 family.
Belongs to the eukaryotic ribosomal protein eL30 family.
Belongs to the methyltransferase superfamily.
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. NOG subfamily.
Involved in the biogenesis of the 60S ribosomal subunit.
Belongs to the eukaryotic ribosomal protein eL19 family.
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP (PubMed:15478799). Has very low activity with CTP, GTP, ITP and UTP and no activity with GMP, CMP, UMP or IMP in vitro (PubMed:15478799).
Inhibited by the dinucleoside pentaphosphate compound P1,P5-di(adenosine-5') pentaphosphate (AP5A).
Belongs to the AAA ATPase family. PCH2 subfamily.
Catalyzes the conversion of xanthine monophosphate (XMP) to GMP in the presence of glutamine and ATP through an adenyl-XMP intermediate, which is the final step of de novo synthesis of GMP (PubMed:17868038, PubMed:21413787, PubMed:32358899, PubMed:26592566). The conversion of XMP to GMP involves the coordinated action of the glutamine amidotransferase (GATase) domain that catalyzes the hydrolysis of the amide side chain of glutamine producing ammonia and the ATP pyrophosphatase (ATPPase) domain that catalyzes the synthesis of adenyl-XMP intermediate from ATP (PubMed:17868038, PubMed:21413787, PubMed:32358899, PubMed:26592566). The ammonia produced by the GATase domain is tunnelled to the ATP-PPase domain where it attacks the adenyl-XMP intermediate generating GMP (PubMed:17868038, PubMed:21413787, PubMed:32358899, PubMed:26592566).
Expressed during the asexual blood stage; expression is low in rings, increases during the trophozoite stage, peaks during the late trophozoites and decreases in schizonts.
Homodimer (via the GMPS ATP-PPase domain).
In absence of glutamine, can use exogenous ammonia to aminate adenyl-XMP intermediate to form GMP in vitro. However, this is likely not physiologically relevant as at cellular pH, ammonia is present as ammonium ion, which cannot serve as a nucleophile required for the reaction.
The GATase domain is allosterically activated by the binding of substrates, ATP and XMP, to the ATPPase domain, thus ensuring that glutamine hydrolysis occurs only when the ATPPase domain is primed to receive ammonia (PubMed:17868038, PubMed:32358899). Inhibited by Na(2+) (PubMed:17868038). Inhibited by the reaction product GMP (PubMed:17868038).
The GMPS ATP-PPase domain catalyzes the condensation of XMP with ATP to form the intermediate product XMP-AMP (PubMed:17868038, PubMed:32358899). ATP binds first, and its binding is required for the subsequent XMP binding (PubMed:17868038).
The glutamine amidotransferase type-1 (GATase) domain hydrolyzes glutamine into glutamate and ammonia where ammonia is then use for the amination of adenyl-XMP intermediate (PubMed:17868038, PubMed:21413787, PubMed:32358899). Upon binding of glutamine, the GATase domain undergoes a conformational change involving an 85 degree rotation, which is required for channeling ammonia from the GATase domain to the GMPS ATP-PPase domain (PubMed:26592566, PubMed:35883427).
Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8 (PubMed:17371404, PubMed:31658303, PubMed:20042598). Essential for parasite blood stage survival (PubMed:20042598).
Belongs to the chaperonin (HSP60) family.
Mediator of sterol homeostasis involved in sterol uptake, trafficking and distribution into membranes.
Regulates also the sphingolipid metabolism.
Belongs to the class-II aminoacyl-tRNA synthetase family.
Belongs to the lipase maturation factor family.
Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
Belongs to the bacterial ribosomal protein bS6 family.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. LepA subfamily.
Promotes mitochondrial protein synthesis. May act as a fidelity factor of the translation reaction, by catalyzing a one-codon backward translocation of tRNAs on improperly translocated ribosomes. Binds to mitochondrial ribosomes in a GTP-dependent manner (By similarity).
Expressed during the asexual blood stage including in trophozoites and schizonts (at protein level).
Thiol protease that cleaves dipeptides from the N-terminus of protein substrates (PubMed:15304495, PubMed:20833209). Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids (PubMed:20833209). Proline cannot occupy the P1 position and arginine or lysine cannot occupy the P2 position of the substrate (PubMed:20833209). Involved in host hemoglobin degradation by generating dipeptides from hemoglobin-derived oligopeptides (PubMed:15304495).
Belongs to the pyridoxal phosphate-binding protein YggS/PROSC family.
Pyridoxal 5'-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6.
Belongs to the flagellar radial spoke RSP3 family.
Adapter protein which binds to its partners, usually via a phosphoserine or phosphothreonine motif (PubMed:23308157, PubMed:32484216, PubMed:32817103). Binding generally results in the modulation of the activity and/or cellular localization of the binding partner (Probable). Via its interaction with CDPK1 and PKAr, involved in merozoite microneme secretion and thus in merozoite invasion of host erythrocytes (PubMed:32817103).
Expressed during parasite asexual blood stages, at the ring, trophozoite and schizont stages and in free merozoites (at protein level).
Homodimer (Probable). Forms a complex composed of CDPK1, PKA regulatory subunit PKAr and 14-3-3I; the complex is formed in merozoites in response to low extracellular level of K(+) and may play a role in microneme secretion (PubMed:32817103). Interacts with CDPK1 (when phosphorylated) in a Ca(2+)-independent manner; the interaction does not regulate CDPK1 catalytic activity but is required for merozoite invasion of host erythrocytes (PubMed:32484216, PubMed:32817103). Interacts with PKA regulatory subunit PKAr (when phosphorylated) in a Ca(2+)-dependent manner (PubMed:32817103). Interacts with histone H3 (when phosphorylated at 'Ser-28' or when phosphorylated at 'Ser-28' and 'Ser-32') (PubMed:23308157).
Although it belongs to the adenylate kinase family, lacks several residues involved in ATP and AMP binding and has no adenylate kinase activity.
Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX.
Belongs to the DNA polymerase type-Y family.
Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family.
Calmodulin is not involved in the mechanism of chloroquine resistance.
Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+) (PubMed:32821880). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases (PubMed:32821880).
Belongs to the bacterial ribosomal protein bL35 family.
Belongs to the class V-like SAM-binding methyltransferase superfamily.
Highly expressed in early trophozoite stages. Expression is then reduced in late trophozoites and elevated again in schizonts.
Histone methyltransferase that specifically represses expression of the surface antigen-coding var genes by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3) on var genes. SETVS-dependent H3K36me3 is specifically involved in var genes silencing, a central step malaria pathogenesis: each parasite contains 60 distinct var genes that each code for a different PfEMP1 protein. During infection, the clonal parasite population expresses only 1 gene at a time, while the 59 other var genes are silenced. The parasite then switches to the expression of a new variant antigen as an immune-evasion mechanism to avoid the host antibody response. Represses expression of both var mRNA and antisense long non-coding RNA.
Leads to expression of all var genes in the ring stage.
Parasites lacking SETVS could be used as an antimalarial vaccine because of its ability to express all PfEMP1 proteins, to which the antibody would provide efficient protective immunity against malaria.
Involved in ribosomal large subunit assembly.
Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome.
This protein may be expected to contain an N-terminal transit peptide but none has been predicted.
Belongs to the DNA polymerase type-B family.
Belongs to the eukaryotic ribosomal protein eS17 family.
Belongs to the universal ribosomal protein uS5 family.
Belongs to the mitochondrion-specific ribosomal protein mL43 family.
Belongs to the eukaryotic ribosomal protein eL29 family.
Necessary for protein translocation in the endoplasmic reticulum.
Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains.
Belongs to the glutamate--cysteine ligase type 3 family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. BUD23/WBSCR22 family.
Belongs to the DEAD box helicase family. DDX1 subfamily.
The helicase domain is involved in the stimulation of RELA transcriptional activity.
In contrast to other metacaspases of the peptidase C14B family, the catalytic histidine and cysteine residues do not appear to be conserved. Contains a serine residue at the position of the canonical catalytic cysteine which may constitute the active site.
Protease that cleaves specifically after arginine or lysine residues.
Belongs to the SNF2/RAD54 helicase family. SWR1 subfamily.
Catalytic component of a chromatin remodeling complex.
Component of a chromatin-remodeling complex.
Catalyzes both the ATP-dependent activation of exogenously supplied lipoate to lipoyl-AMP and the transfer of the activated lipoyl onto the lipoyl domains of lipoate-dependent enzymes (PubMed:17244193, PubMed:25116855, PubMed:28543853). In the mitochondrion, functions as a redox switch between two lipoylation routes (PubMed:25116855). Senses the oxidation state of lipoate and determines which downstream enzymes will be lipoylated (PubMed:25116855). In low reducing conditions, uses lipoate in its oxidized ring form to lipoylate glycine cleavage system H-protein GCVH (PubMed:17244193, PubMed:25116855, PubMed:28543853). In high reducing conditions and together with LipL2, uses reduced lipoate (dihydrolipoate) to lipoylate the E2 component of the branched chain alpha-ketoacid dehydrogenase complex BCKDH-E2/BCDH and the E2 component of the alpha-ketoglutarate dehydrogenase complex KDH. LipL1 is responsible for catalysing the activation of lipoate, forming lipoyl-AMP while LipL2 is required but is not capable of catalyzing this reaction (PubMed:17244193, PubMed:25116855).
Expressed during the asexual blood stage, predominantly at the ring and schizont stages (at protein level).
Inhibited by the lipoate analog 8-bromo-octanoate (BrO) (PubMed:17244193). Catalytic activity is increased in the presence of Mg(2+) (PubMed:17244193).
Belongs to the inositol phosphokinase (IPK) family.
Belongs to the universal ribosomal protein uL15 family.
Belongs to the universal ribosomal protein uL14 family.
Belongs to the eukaryotic ribosomal protein eL14 family.
Belongs to the Rieske iron-sulfur protein family.
The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins.
Belongs to the Orn/Lys/Arg decarboxylase class-II family.
Belongs to the eukaryotic AdoMetDC family.
Belongs to the CDP-alcohol phosphatidyltransferase class-I family.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome.
RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation.
Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.
Belongs to the peroxisomal membrane protein PXMP2/4 family.
Autocleaved into a p16 prodomain form and two mature forms p44 and p51.
During the asexual blood stage, processes key proteins essential for merozoite egress and invasion of host erythrocytes (PubMed:29074775, PubMed:32109369). Cleaves and activates proteases SUB1 and SUB2 (PubMed:29074775, PubMed:32109369). May process members of the EBL and Rh protein families (PubMed:32109369). Also cleaves apical membrane protein AMA1 (PubMed:29074775). During the mosquito vector stage and probably in ookinetes, cleaves CelTOS (PubMed:29074775).
Inhibited by small molecule 49c (PubMed:29074775). Inhibited by small molecules WM382, WM4, and WM5 (PubMed:32109369).
Component of the hemozoin formation complex (HFC) composed of falcipain 2, plasmepsins PMII, PMIII/HAP and PMIV, heme detoxifying protein HDP and falcilysin FLN (PubMed:23471987). The HFC complex is involved in hemoglobin degradation and detoxification of heme in the food vacuole during the asexual blood stage (PubMed:23471987). Interacts with falcipain 2; the interaction is direct and enhances HDP catalytic activity (PubMed:23471987). Interacts with host hemoglobin (PubMed:28949547).
HDP is critical for survival, suggesting it could be a potential malaria drug target.
Heme detoxifying enzyme that converts heme to crystalline hemozoin (beta-hematin) to protect the organism from the toxic effects of heme (PubMed:18437218, PubMed:23471987, PubMed:25138161, PubMed:28949547). During its development, P.falciparum proteolyzes vast amounts of host hemoglobin, leading to heme release (PubMed:18437218).
In the C-terminal section; belongs to the peptidase M41 family.
In the N-terminal section; belongs to the AAA ATPase family.
Belongs to the ribulose-phosphate 3-epimerase family.
Belongs to the WD repeat coronin family.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. EngB GTPase family.
Belongs to the mitochondrion-specific ribosomal protein mL54 family.
Part of the complex catalyzing the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, the first step of GPI biosynthesis.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
Catalyzes the attachment of serine to tRNA(Ser). Is also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (By similarity).
Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.
Homodimer. The tRNA molecule binds across the dimer (By similarity).
Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.
Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family.
Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft (By similarity).
Belongs to the endoribonuclease YbeY family.
Belongs to the steroid 5-alpha reductase family. Polyprenol reductase subfamily.
Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism.
Belongs to the bacterial histone-like protein family.
Component of the origin recognition complex (ORC) (By similarity). Interacts with PCNA1; the interaction occurs during the trophozoite stage but not at the late schizont stage (PubMed:18554328).
Component of the origin recognition complex (ORC) that binds origins of replication.
Expressed during the asexual blood stage, specifically during the trophozoite and schizont stages (at protein level).
Belongs to the pseudouridine synthase Pus10 family.
Component of the general transcription and DNA repair factor IIH (TFIIH) core complex which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA.
Expressed during the asexual blood stage, including rings, trophozoites, schizonts (at protein level) (PubMed:22355110, PubMed:29241041). Expressed in male and female gametocytes (at protein level) (PubMed:22355110).
Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (By similarity). May regulate protein translation in response to amino acid starvation (Probable). May regulate protein at various stages of parasite development (Probable).
Phosphorylated at Ser-59 by eIK1 in response to amino acid starvation (PubMed:19435497). Phosphorylates at Ser-59 in schizonts and gametocytes but not in rings and young trophozoites (PubMed:22355110, PubMed:29241041). Phosphorylates at Ser-59 by eIK2 in salivary gland sporozoites but not in midgut and hemocoel sporozoites (By similarity). Dephosphorylated at Ser-59 by UIS2 (PubMed:26735921). Phosphorylation of eIF2alpha subunit of the pre-initiation complex eIF2 inhibits recycling of inactive eIF2-GDP to active eIF2-GTP by limiting the activity of the guanine nucleotide exchange factor eIF2B and thus, inhibits protein translation (PubMed:19435497).
Belongs to the universal ribosomal protein uS7 family.
Belongs to the FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.
Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Belongs to the eukaryotic ribosomal protein eS8 family.
Although it belongs to the kinase superfamily, contains an asparagine residue at the position of the canonical catalytic aspartic acid and does not have kinase activity (PubMed:31148576). However, can bind ATP (PubMed:31148576).
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Interacts (via RVxF motif 1 and/or 2) with phosphatase PP1C (PubMed:31148576). May interact (via SAM domain) with SERA5 (via C-terminus) (PubMed:31148576).
The protein kinase domain is predicted to be catalytically inactive (By similarity). There is a second N-terminal lobe-like kinase domain at residues 830-1095 that contains functional ATP binding sites (PubMed:31148576).
Belongs to the glycosyl hydrolase 18 family.
Endochitinase that cleaves beta-1,4-linkages between tri- and tetramers of N-acetylglucosamine (GlcNAc) from penta- and hexameric chitin oligomers (PubMed:10570198, PubMed:16088838, PubMed:35481637). Does not cleave smaller chitin oligosaccharides (PubMed:10570198). Required to cross the acellular, chitin-containing peritrophic matrix (PM) which is formed around the ingested blood meal in the mosquito midgut allowing the ookinete to invade the mosquito gut epithelium (PubMed:11349075).
Expressed in the zygote (at protein level) (PubMed:11035760). Expressed in ookinetes (at protein level) (PubMed:10570198, PubMed:11035760, PubMed:11349075, PubMed:33489941).
Forms a hetero-multimeric, high molecular weight complex composed of at least CHT1, SOAP AND WARP (PubMed:33489941). Within the complex, may interact with WARP via a disulfide bond (PubMed:33489941).
Potential target for the development of transmission blocking vaccines (PubMed:16088838). Antibodies against CHT1 neutralize CHT1 catalytic activity and when fed with the parasite prevent parasite development in the mosquito midgut (PubMed:16088838).
Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment.
May protect the parasite against attack by the host immune system by immunomodulation.
Blood stage antigen transported to the erythrocyte surface.
Part of the multisubunit TRAPP (transport protein particle) complex.
Does not affect merozoite invasion of host erythrocytes, either untreated or treated with neuraminidase, trypsin or chymotrypsin.
During the asexual blood stage, binds to a chymotrypsin sensitive, neuraminidase and trypsin resistant receptor on the surface of the host erythrocyte (PubMed:21628513). Despite its binding capacity, appears to be dispensable for merozoite invasion of host erythrocytes (PubMed:12606570, PubMed:21698217).
During the asexual blood stage, binds to a trypsin-resistant and chymotrypsin and neuraminidase sensitive receptor on the surface of the host erythrocyte.
Expressed during parasite asexual blood stages, specifically at the late schizont stage prior to merozoite release and in free merozoites (at protein level).
Forms a heterodimer composed of the 285 kDa and the 85 kDa forms.
Proteolytically processed into multiple fragments following schizont rupture (PubMed:21628513, PubMed:12228308, PubMed:21698217). In the mature schizont stage prior to merozoite release, full length RH2b is processed post-Golgi into C-terminal 285 kDa and N-terminal 85 kDa forms (PubMed:21628513, PubMed:21698217). During merozoite invasion of host erythrocytes, further processing occurs generating a 140 kDa C-terminal form (PubMed:21628513). At the same time, the C-terminal transmembrane region is probably cleaved, probably by a rhomboid protease, to shed all the different processed protein forms from the membrane leaving a transmembrane 7 kDa form on the merozoite surface (PubMed:21628513, PubMed:21698217).
RH2a expression levels greatly vary between isolates; levels are high in isolates 3D7, T996, HB3, D10, 7G8, K1, Pf120 and W2mef, and undetectable in isolates MCAMP, FCB1, T994 and FCR3 (PubMed:12228308, PubMed:12606570). A similar variation in expression affects other reticulocyte-binding proteins such as RH2b and RH1 (PubMed:12228308, PubMed:12606570). The expression pattern of RH1, RH2a and RH2b allows the strain to use different invasion pathways to enter erythrocytes (Probable). This provides a mechanism of phenotypic variation to evade host immune responses and to adapt to the polymorphic nature of the erythrocyte receptors in human populations (Probable).
Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. RHD3 subfamily.
Probable GTP-binding protein involved in generating and maintaining the structure of the tubular endoplasmic reticulum network.
Belongs to the phosphohexose mutase family.
Belongs to the acetyltransferase family. NAA40 subfamily.
Binds 1 divalent cation per subunit. Mg(2+) or Mn(2+).
Catalyzes the NADPH-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).
Inhibited by fosmidomycin and its derivatives.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
Belongs to the diphthine synthase family.
S-adenosyl-L-methionine-dependent methyltransferase that catalyzes four methylations of the modified target histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester. The four successive methylation reactions represent the second step of diphthamide biosynthesis.
Catalyzes the ferrous insertion into protoporphyrin IX.
Acts as a co-chaperone and mediates the association of the chaperones HSP70 and HSP90 probably facilitating substrate transfer from HSP70 to HSP90 (PubMed:22005844, PubMed:26267894). Stimulates HSP70 ATPase activity and, in contrast, inhibits HSP90 ATPase activity (PubMed:31525467).
Expressed during the parasite blood stage, in trophozoites (at protein level).
Monomer (PubMed:32343703). Homodimer (PubMed:26267894, PubMed:31525467). Forms a complex composed of HOP and chaperones HSP70 and HSP90; the interaction is stronger in the absence of ATP (PubMed:22005844). Interacts (via TPR 1, 2, 3, 7, 8 and 9 repeats) with HSP70 (via C-terminus); the interaction is direct and is stronger in the absence of ATP (PubMed:26267894). Interacts (via TPR 4, 5 and 6 repeats) with HSP90 (via C-terminus); the interaction is direct (PubMed:26267894).
Showed to form heterodimers (PubMed:26267894, PubMed:31525467). However in a later study, showed to exist predominantly as a monomer (PubMed:32343703).
The TPR repeats form 3 domains; the TPR 1 domain is composed of TPR 1, 2 and 3 repeats, the TPR2A domain of TPR 4, 5 and 6 repeats and TPR2B domain of TPR 7, 8 and 9 repeats.
Belongs to the prefoldin subunit alpha family.
Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.
Heterohexamer of two PFD-alpha type and four PFD-beta type subunits.
Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis.
Activated by calcium (PubMed:20466936). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-285, which leads to the kinase activation (By similarity).
Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (PubMed:20466936, PubMed:31915223). Plays a central role in host erythrocytes and hepatocytes infection cycles (PubMed:20466936, PubMed:29487234). During the liver stage, involved in sporozoite motility and thus in sporozoite invasion of host hepatocytes, probably together with CDPK1 and CDPK4 (By similarity). Involved in merosome egress from host hepatocytes, probably together with CDPK4 (By similarity). Required for the release of hepatic merozoites from merosomes in the host blood stream (By similarity). During the asexual blood stage, required for merozoite egress from host erythrocytes by triggering microneme secretion (PubMed:20466936, PubMed:29487234). Phosphorylates transporter NPT1 at late schizont stage (PubMed:31915223).
Expressed at the blood stage in schizonts (at protein level).
Impaired replication in host erythrocytes (PubMed:20466936). Parasite development is arrested at the late schizont stage before the rupture of the parasitophorous vacuole membrane rupture, however, the daughter merozoites are fully mature and their number per schizont is not affected (PubMed:20466936, PubMed:29487234). Loss of secretion of AMA1-containing and EBA175-containing micronemes (PubMed:29487234). SUB1-mediated processing of AMA1 and SERA5, which is part of the protease cascade involved in parasite egress, is reduced (PubMed:29487234). At the late schizont stage, phosphorylation of several transmembrane- and membrane-associated proteins and proteins associated with transport activity is reduced (PubMed:31915223).
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (By similarity). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (By similarity).
Belongs to the helicase family. RAD3/XPD subfamily.
Activated by cGMP (PubMed:12068803, PubMed:12817987, PubMed:26149123, PubMed:29251493, PubMed:25646845, PubMed:31239348). Not activated by cAMP (PubMed:12068803, PubMed:12817987). cGMP binding allosterically triggers a conformational change at the alpha C-helix of cGMP-binding domain 4, which bridges the regulatory and catalytic domains, causing the capping triad, composed of Arg-484, Gln-532 and Asp-533, to form and stabilize the active conformation (PubMed:29251493, PubMed:25646845). The cGMP-binding domains acts cooperatively to activate PKG (PubMed:29251493, PubMed:12817987).
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily.
Expressed during the parasite blood stage, expression is low at the ring stage and in early trophozoites, then increases during the parasite maturation to peak at the late schizont stage (at protein level) (PubMed:31239348, PubMed:19915077, PubMed:23139764, PubMed:12068803). Expression is low in gametocytes (at protein level) (PubMed:23139764).
Serine/threonine protein kinase which acts as a downstream effector of the second messenger cGMP (PubMed:12068803, PubMed:12817987, PubMed:26149123). Controls the release of Ca(2+) from intracellular stores by regulating phosphoinositide biosynthesis (PubMed:24594931). Ca(2+) signals are essential for merozoite and sporozoite invasion and egress from host hepatocytes and erythrocytes, and, in the mosquito vector, for gametocyte activation, and ookinete and sporozoite motility (PubMed:24594931). During the host liver stage, regulates the initial invasion of host hepatocytes by sporozoites by regulating sporozoite motility and microneme exocytosis (By similarity). Following parasite development in the hepatocytes, required for the release of merosomes, a vesicle containing the mature merozoites (By similarity). During the asexual blood stage, required for the progression from schizont to the ring stage following merozoite invasion of host erythrocytes and for merozoite egress (PubMed:19915077, PubMed:26149123, PubMed:25646845). Regulates merozoite egress by promoting the release of exonemes and micronemes which contain proteins essential for egress (PubMed:23675297). Phosphorylates CDPK1 predominantly at the late schizont stage; phosphorylation at 'Ser-64' regulates CDPK1 protein-protein interaction and phosphorylation at 'Thr-231' may regulate CDPK1 kinase activity (PubMed:26149123). Phosphorylates MyoA at 'Ser-19' (PubMed:26149123). In the mosquito vector, required for the initiation of gametogenesis induced by xanthurenic acid, specifically the gametocyte differentiation from the crescent-shaped form to the spherical form (PubMed:18532880). Required for the gliding motility of ookinetes to reach and penetrate the midgut epithelium by promoting Ca(2+)-mediated activation of CDPK1 and CDPK4 (By similarity). Also required for microneme secretion in ookinete by promoting Ca(2+)-mediated activation of CDPK3 (By similarity).
The autoinhibitory segment (AIS) interacts with the active site and inhibits catalytic activity.
The cNMP-binding domains 1, 2 and 4 bind preferentially cGMP (PubMed:25646845). The cNMP-binding domain 4 binds cGMP with the highest affinity and is highly selective for cGMP (PubMed:29251493, PubMed:25646845, PubMed:31239348). The cNMP-binding domain 3 does not bind cGMP but is required for cGMP-dependent catalytic activity (PubMed:12817987). The cNMP-binding domains 1, 2 and 4 can bind cAMP but with less affinity (PubMed:25646845).
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. TRM7 subfamily.
Methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs.
Belongs to the STXBP/unc-18/SEC1 family.
Belongs to the replication factor A protein 1 family.
Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
Belongs to the aspartate/ornithine carbamoyltransferase superfamily.
Belongs to the V-ATPase C subunit family.
Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment. Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity.
V-ATPase is a heteromultimeric enzyme composed of a peripheral catalytic V1 complex (components A to H) attached to an integral membrane V0 proton pore complex.
Binds 2 magnesium ions per subunit (By similarity). Is also active with manganese (in vitro) (By similarity).
Catalyzes the synthesis of the second messenger cGMP from GTP (Probable). In asexual blood stage schizonts, required for cGMP production which is essential for PKG activation, PKG-dependent Ca(2+) release, and ultimately merozoite egress from host erythrocytes (PubMed:33500341).
During the parasite blood stage, highly expressed in mature schizonts and in gametocytes.
In the C-terminal section; belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
In the N-terminal section; belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
Knockout at the asexual blood stage causes growth arrest (PubMed:33500341). Mature schizonts accumulate in host erythrocytes due to a defect in merozoite egress (PubMed:33500341). Lack of swelling or rupture of the parasitophorous vacuole membrane and, no Ca(2+) release from intracellular stores and no secretion of protease SERA5 (PubMed:33500341). Mature schizonts fail to synthesize cGMP; no defect in cAMP levels (PubMed:33500341).
The N-terminus contains a P-type ATPase-like domain which may be important for guanylate cyclase activity.
Unlike the two guanylate cyclase domains of GCbeta, the guanylate cyclase domains 1 and 2 of GCalpha lack catalytic activity when expressed on their own or in combination.
Belongs to the V-ATPase H subunit family.
Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation.
Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily.
Belongs to the protein prenyltransferase subunit alpha family.
Attenuated parasites that cannot commit to infection, even when they encounter with hepatocytes, resulting in continuous traversal of hepatocytes.
Involved in sporozoite infection of hepatocytes and replication therein.
Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.
Belongs to the eukaryotic ribosomal protein eL18 family.
Belongs to the adaptor complexes medium subunit family.
Catalyzes the formation of pyridoxal 5'-phosphate from ribose 5-phosphate (RBP), glyceraldehyde 3-phosphate (G3P) and ammonia. The ammonia is provided by Pdx2. Can also use ribulose 5-phosphate and dihydroxyacetone phosphate as substrates, resulting from enzyme-catalyzed isomerization of RBP and G3P, respectively.
Homohexamer and homododecamer. In the presence of Pdx2, forms a dodecamer of heterodimers.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. EngA (Der) GTPase family.
Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.
Belongs to the ribose 5-phosphate isomerase family.
Involved in the first step of the non-oxidative branch of the pentose phosphate pathway. It catalyzes the reversible conversion of ribose-5-phosphate to ribulose 5-phosphate.
Binds 1 heme c group covalently per subunit.
Required for proper 27S pre-rRNA processing and 60S ribosome subunit assembly.
Belongs to the NADH dehydrogenase family.
Antibodies against CERLI2 severely reduces parasitemia, suggesting that CERLI2 is a potential vaccine candidate.
During parasite asexual blood stages, expressed in trophozoites and at the schizont stage (at protein level).
Impairs merozoite invasion of host erythrocytes at, or prior to, the formation of the tight junction (PubMed:35140336). Merozoite development and egress following schizont rupture are not affected (PubMed:35140336). Inhibits rhoptry bulb RAP1 processing but not secretion of rhoptry neck proteins RH4 and RON4 (PubMed:35140336). Causes defects in rhoptry morphology which are narrower and more elongated (PubMed:35140336). No defect in microneme secretion (PubMed:35140336).
Plays an important role in rhoptry physiology and thus is essential for merozoite invasion of host erythrocytes.
The number of deca-peptide repeats in the C-terminus varies across P.falciparum strains (PubMed:19777263). Strain 3D7 has 12 copies; Dd2 has 14 copies; Hondura-1, FCC1, FCC2, and T996 have 17 copies; and strain D10 and FCR3 have 19 copies (PubMed:19777263).
Belongs to the proteasome subunit S2 family.
Belongs to the UbiA prenyltransferase family.
Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration.
Belongs to the proteasome inhibitor PI31 family.
Belongs to the eukaryotic ribosomal protein eS6 family.
Belongs to the dynactin subunit 4 family.
Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.
Belongs to the phospholipid scramblase family.
Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry (PubMed:33974939). Preferentially, mediates calcium-dependent phosphatidylethanolamine externalization (PubMed:33974939). During the liver stage, plays a role in the interaction with, and thus invasion of, host hepatocytes (PubMed:34799567). Dispensable for host erythrocyte invasion and asexual parasite development (PubMed:33974939).
Expressed in sporozoites (at protein level) (PubMed:34799567). Expressed during the asexual blood stage, including in rings, trophozoites and schizonts (PubMed:33974939). Expressed in gametocytes (PubMed:33974939).
Forms homooligomers in the presence of calcium.
No defect in asexual blood stage growth.
Belongs to the proteasome subunit S9 family.
Belongs to the DNA glycosylase MPG family.
Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.
Belongs to the universal ribosomal protein uL11 family.
Belongs to the cytochrome c-type heme lyase family.
Lyase that catalyzes the covalent linking of the heme group to the cytochrome C apoprotein to produce the mature functional cytochrome.
Belongs to the polyadenylate-binding protein type-1 family.
Conditional knockout at the merozoite stage, does not cause any defect in schizont morphology, merozoite number and maturation initially. During the subsequent invasive cycle in host erythrocytes, merozoite replication is severely impaired due to a premature rupture of the parasitophorous vacuole and erythrocyte membranes resulting in an inefficient dispersal of released merozoites.
Expressed during parasite asexual blood stages, specifically in late trophozoite and schizont stages (at protein level).
In contrast to other serine-repeat antigen proteins (SERA) of the peptidase C1 family, contains a serine residue at the position of the canonical catalytic cysteine and has been shown to lack protease activity. However, other studies show that it has protease activity towards synthetic peptides in vitro (PubMed:13679369, PubMed:24769454, PubMed:29716996).
Interacts (via C-terminus) with human VTN (via hemopexin repeat 2); may form heterotetramers of two VTN and SERA5 P47 heterodimers; the interaction may protect merozoites from phagocytosis by host monocytes; VTN glycosylation appears to be dispensable for the interaction.
Just prior to merozoite egress from host erythrocytes, proteolytically cleaved into multiple fragments (PubMed:18083098, PubMed:25599609, PubMed:24769454). Cleaved by SUB1 into p47 and p73, p73 is further cleaved by SUB1 into p56 and p18 and p56 is further processed into p50 by an unidentified protease (PubMed:25599609, PubMed:18083098). p47 remains covalently associated with p18 via disulfide bond (PubMed:25599609). p47 can be processed into p25n and p25c by SUB1 (PubMed:25599609, PubMed:18083098). p25c and p25n remain associated with p18 (PubMed:25599609). Proteolytic processing is essential for merozoite egress from host erythrocytes (PubMed:28683142). The cleavage of the propeptide to produce p50 is necessary for protease activity and to promote merozoite egress (PubMed:24769454).
May interact (via C-terminus) with PTKL (via SAM domain).
May prevent merozoite phagocytosis by host monocytes via interaction with host VTN at the merozoite surface (By similarity). Plays a role in parasite growth (By similarity).
Monomer (PubMed:13679369, PubMed:25599609). Interacts with kinase CPK1/CDPK1 at the schizont stage (PubMed:29716996).
Phosphorylation by CPK1/CDPK1 increases SERA5 protease activity towards a synthetic peptide in vitro.
Plays an essential role during the asexual blood stage development by controlling the kinetics of merozoite egress from host erythrocytes (PubMed:25599609, PubMed:28683142). Specifically, prevents premature rupture of the parasitophorous vacuole and host erythrocyte membranes (PubMed:28683142).
Produced during parasite asexual blood stages, specifically at the merozoite stage just prior to egress (at protein level).
Protease activity is controversial (PubMed:25599609). Has been shown in a number of studies to have protease activity towards a synthetic peptide in vitro (PubMed:13679369, PubMed:24769454, PubMed:29716996). Has also been shown to lack protease activity towards a synthetic peptide in vitro (PubMed:25599609).
Belongs to the eukaryotic ribosomal protein eS25 family.
Belongs to the EF-1-beta/EF-1-delta family.
Belongs to the ATPase gamma chain family.
F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c.
Belongs to the universal ribosomal protein uS17 family.
Belongs to the Mediator complex subunit 14 family.
Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. May also be involved in ribosome biogenesis.
Monomer. Associates with the 60S ribosomal subunit.
Belongs to the lyase 1 family. Adenylosuccinate lyase subfamily.
Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily.
Belongs to the 2-oxoacid dehydrogenase family.
Belongs to the class-II aminoacyl-tRNA synthetase family. ProS type 3 subfamily.
Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (PubMed:25817387, PubMed:27798837). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro) (PubMed:14663147). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala) (PubMed:14663147).
Consists of four domains: the N-terminal editing domain, the N-terminal catalytic domain, the anticodon-binding domain and the C-terminal extension (Probable). The first domain (about residues 1-163) is required for editing of incorrectly charged tRNA (PubMed:14663147). When it is deleted the enzyme shows pronounced misacylation of tRNA(Pro) with alanine (PubMed:14663147).
Expressed during the asexual blood stage including at the ring stage and in trophozoites and schizonts (at protein level).
Inhibited by the quinazolinone-based compound febrifugine from the Chinese plant Dichroa febrifuga which is used to treat malaria-associated fever (PubMed:25817387, PubMed:27798837). Also inhibited by febrifugine derivatives such as halofuginone (PubMed:25817387, PubMed:27798837).
A potassium ion appears to reside in the active site during hydrolysis and leaves together with the inorganic phosphate Pi. K(+) does not activate Pi release; however, it may be relevant for ATP hydrolysis.
ACT1 and ACT2 differ in their polymerization, filament stability and helical structure (PubMed:24743229). Unlike mammalian actin, Apicomplexa actins do not form long and stable filaments (PubMed:24743229).
ATP hydrolysis occurs in the polymeric state (PubMed:24743229). Unlike for mammalian actin, ATP hydrolysis occurs also in the monomeric form and the release of inorganic phosphate (Pi) is more efficient (PubMed:24743229).
Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm (PubMed:24743229, PubMed:28923924, PubMed:31199804). Polymerizes into shorter and less stable actin filaments compared to ACT2/actin-2; this is thought to facilitate gliding motility and host cell invasion (PubMed:24743229, PubMed:28923924). Has ATPase activity (PubMed:24743229, PubMed:31199804). ATP hydrolysis leads to the formation of a stable intermediate ADP-inorganic phosphate (Pi) actin, which is followed by the release of Pi (Probable). ATP hydrolysis affects filament stability; ADP-bound actin depolymerizes much faster than ATP- or ADP-Pi-bound actin (Probable). Plays an essential role during the asexual blood stage (PubMed:28810863). At the segmented schizont stage, required for apicoplast migration and segregation into individual daughter merozoites (PubMed:28810863). Also, required for the separation of daughter merozoites in the final stages of cytokinesis (PubMed:28810863). Essential for merozoite invasion of, but not adhesion to or reorientation towards, host erythrocytes (PubMed:28810863).
Conditional knockout at the ring stage results in the production of merozoites; however, these merozoites fail to start a new infection cycle due to a failure to invade new host erythrocytes (PubMed:28810863). During schizogony, daughter merozoite development and segmentation is abnormal and is characterized by the presence of aberrant membranous pockets adjacent to the food vacuole (PubMed:28810863). Apicoplasts have few branches and collapse close to the food vacuole failing to migrate to individual daughter cells (PubMed:28810863). No defect in secretory organelles or mitochondria and the formation of Maurer's clefts in the host cytoplasm is normal (PubMed:28810863). Egress from host erythrocytes is normal; however, some merozoites stayed conjoined, remaining connected to each other and to the central food vacuole (PubMed:28810863). No defect in microneme secretion (PubMed:28810863). Merozoite attachment to the host erythrocyte, reorientation and secretion of RON proteins are normal (PubMed:28810863). However, the formation of the circular junction between the parasite and host cell membranes is impaired and merozoites are incapable of deforming and invading host erythrocytes (PubMed:28810863). Production of gametocytes is normal (PubMed:28810863).
Expressed during the asexual blood stage, including in trophozoites, schizonts and merozoites (at protein level) (PubMed:28810863). Expression increases at the late trophozoite stage (at protein level) (PubMed:28810863).
Monomer (G-actin) (PubMed:24743229). Oligomer (F-actin) (PubMed:24743229, PubMed:28923924). Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (PubMed:24743229, PubMed:28923924). Unlike for mammalian monomeric actin, parasite monomeric actin is able to induce oligomerization in the presence of ATP or ADP (PubMed:24743229). Mg(2+), which is used to coordinate ATP, is required for polymerization (PubMed:24743229). Interacts with MyoA (PubMed:33767187). Interacts with DNase I with low affinity (By similarity).
Belongs to the universal ribosomal protein uL5 family.
ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the membrane-bound receptor, and returning it to the cytosol to initiate a new round of targeting.
Component of the 30S ribosomal translation pre-initiation complex which assembles on the 30S ribosome in the order IF-2 and IF-3, IF-1 and N-formylmethionyl-tRNA(fMet); mRNA recruitment can occur at any time during PIC assembly.
One of the essential components for the initiation of protein synthesis. Stabilizes the binding of IF-2 and IF-3 on the 30S subunit to which N-formylmethionyl-tRNA(fMet) subsequently binds. Helps modulate mRNA selection, yielding the 30S pre-initiation complex (PIC). Upon addition of the 50S ribosomal subunit IF-1, IF-2 and IF-3 are released leaving the mature 70S translation initiation complex.
Belongs to the universal ribosomal protein uS19 family.
Belongs to the eukaryotic GSH synthase family.
Belongs to the pseudouridine synthase TruD family.
Belongs to the type II topoisomerase family.
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Component of the small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs).
Required for ribosome biogenesis. Part of a complex which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Pseudouridine ("psi") residues may serve to stabilize the conformation of rRNAs.
Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.
Belongs to the RNA polymerase beta' chain family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
Belongs to the V-ATPase 116 kDa subunit family.
Essential for the invasive blood stages of the parasite. Binds to proline rich sequences in various regulatory formin-like proteins and also to membrane phospholipids. Binds to actin and affects the structure of the cytoskeleton. Weakly sequesters actin monomers (By similarity).
The actin binding residues are poorly conserved between Plasmodium and other organisms. The Plasmodium-specific profilin mini-domain may have a role in binding to membrane phospholipids.
Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine in 18S rRNA. It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi).
Belongs to the TDD superfamily. TSR3 family.
Belongs to the eukaryotic/archaeal RNase P protein component 1 family.
Interacts with EME1 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, D-loops, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication fork intermediates. May be required in meiosis for the repair of meiosis-specific double strand breaks subsequent to single-end invasion (SEI).
Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. SPB1 subfamily.
Probable methyltransferase involved in the maturation of rRNA and in the biogenesis of ribosomal subunits.
Acetylation at Lys-101 by ESCO1 is important for genome stability and S phase sister chromatid cohesion.
Belongs to the SMC family. SMC3 subfamily.
Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement (By similarity).
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC1A or SMC1B, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure (By similarity).
At the asexual blood stage, causes an accumulation of vesicles at the Maurer's clefts (PubMed:35930605). Aberrant knob morphology and distribution; knobs are fewer and larger (PubMed:35930605). EMP1 delivery to the Maurer's clefts is normal; however, EMP1 delivery to the host erythrocyte cell surface is abolished (PubMed:35930605).
During the asexual blood stage, plays an essential role in the recruitment and/or formation of EMP1-containing vesicles at the Maurer's clefts and their subsequent transfer to the host erythrocyte cell membrane.
Expressed during the asexual blood stage, including rings and trophozoites (at protein level).
May interact with MESA (PubMed:35930605). May interact with J-dot compartment protein PF3D7_0801000 (PubMed:35930605).
The P.falciparum Export Element (PEXEL) motif, also known as the vacuolar transport signal (VTS), is a pentameric sequence (RxLxE/Q/D) required for the translocation of proteins across the parasitophorous vacuole membrane (Probable). In the endoplasmic reticulum, the motif is cleaved after the leucine residue and the N-terminus is N-acetylated (By similarity).
Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.
Belongs to the adenosylhomocysteinase family.
Belongs to the activator 1 small subunits family.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2.
Belongs to the GTP-binding elongation factor family. EF-G/EF-2 subfamily.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.
Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome.
Catalyzes the interconversion of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, a source of one-carbon units used by thymidylate synthase to convert dUMP to dTMP for DNA synthesis (PubMed:11071283, PubMed:19591883, PubMed:24914963). Binds to its own mRNA and to the mRNA of bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) in vitro; the physiological relevance of this interaction is not clear (PubMed:19591883).
Expressed during the parasite erythrocyte stages, namely in trophozoites and schizonts.
Redox regulation; active in reducing conditions, inactive in oxidizing conditions. The reduction of the cysteine pairs allows the access binding of the tetrahydrofolate substrate to its binding site. This mechanism appears to be unique to Plasmodium species.
Belongs to the snRNP core protein family.
Belongs to the glycosyltransferase 2 family.
Component of the dolichol-phosphate mannose (DPM) synthase complex.
Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins.
Apurinic/apyrimidinic (AP) endonuclease activity is maximal at low Mg(2+) (0.5-2 mM) with no activity seen at high concentrations (more than 10 mM) (PubMed:33743509). 3'-5' exonuclease activity is maximal in the range of 0.5-2 mM Mg(2+) with activity seen up to 10 mM Mg(2+) (PubMed:33743509).
Belongs to the DNA repair enzymes AP/ExoA family.
Expressed during the asexual blood stage, including trophozoites (at protein level).
May be proteolytically cleaved into a 64 kDa form.
Multifunctional protein that plays a central role in mitochondrial DNA base excision repair (BER) pathway induced by oxidative stress. Has apurinic/apyrimidinic (AP) endonuclease activity towards double-stranded DNA (dsDNA) (PubMed:33743509). Has nucleotide incision repair (NIR) activity; acts on dsDNA with oxidized bases thymine glycol and 5,6-dihydro-2'-deoxyuridine (PubMed:33743509). Has 3'-5' exonuclease; can use dsDNA templates with 3'-OH termini including blunt-end, gapped and mismatched 3'-recessed (PubMed:33743509). Has 3'-phosphatase activity; cleaves 3'-phosphate from blunt, recessed and gapped dsDNA templates, followed by 3'-5' exonuclease activity (PubMed:33743509). Has RNase H-like activity; cleaves RNA on 3'-recessed RNA-DNA duplex (PubMed:33743509). Plays a role in merosome infection of host erythrocytes (By similarity).
Probably binds two magnesium or manganese ions per subunit.
Belongs to the SMC family. RAD50 subfamily.
Essential component of the MRN complex, a complex that possesses single-stranded DNA endonuclease and 3' to 5' exonuclease activities, and plays a central role in double-strand break (DSB) repair, chromosome morphogenesis, DNA repair and meiosis. In the complex, it mediates the ATP-binding and is probably required to bind DNA ends and hold them in close proximity (By similarity).
Probable component of the MRN complex with MRE11.
The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11 homodimer (By similarity).
Catalytic activity is increase by myristoylated ARF1 (PubMed:19171150). Phosphatidic acid has no effect on catalytic activity (PubMed:19171150).
Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes.
Expressed during the asexual blood stage (at protein level) (PubMed:19171150). Expressed in gametocytes (at protein level) (PubMed:19171150).
Belongs to the cytidylyltransferase family.
Belongs to the FNT transporter (TC 2.A.44) family.
Belongs to the 2Fe2S plant-type ferredoxin family.
Detected in trophozoite and schizont stages (at protein level).
Ferredoxins are iron-sulfur proteins that transfer electrons in a wide variety of metabolic reactions (PubMed:16289098). By transferring electrons to 4-hydroxy-3-methylbut-2-enyl diphosphate reductase LytB/IspH, plays a role in the terminal step of the DOXP/MEP pathway for isoprenoid precursor biosynthesis (PubMed:16289098).
Belongs to the universal ribosomal protein uS4 family.
Belongs to the acyl carrier protein (ACP) family.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.
Belongs to the tRNA pseudouridine synthase TruA family.
Belongs to the UTP23/FCF1 family. FCF1 subfamily.
Belongs to the WD repeat G protein beta family. Ribosomal protein RACK1 subfamily.
Belongs to the NFYB/HAP3 subunit family.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.
Belongs to the purine/pyrimidine phosphoribosyltransferase family.
Component of the origin recognition complex (ORC) (By similarity). Interacts (via PIP-box) with PCNA1; the interaction occurs during DNA replication in trophozoites (PubMed:18554328, PubMed:19633266).
Component of the origin recognition complex (ORC) that binds origins of replication and thus may regulate the initiation of DNA replication (Probable). DNA-binding may not be ATP-dependent (PubMed:19633266). In a SIR2A/Sir2-dependent manner, binds to and silences telomers and subtelomeric repeat regions (TAREs) (PubMed:18525026, PubMed:22379140, PubMed:24018145). In a SIR2A/Sir2-dependent manner, binds to promoters of var genes localized next to TAREs resulting in their silencing (PubMed:22379140).
Expressed during the asexual blood stage, specifically during the late trophozoite and early schizont stages (at protein level) (PubMed:16216221, PubMed:18525026, PubMed:18554328, PubMed:19633266, PubMed:22379140, PubMed:26094711). Some expression has been found also at the ring stage (at protein level) (PubMed:18525026, PubMed:18554328, PubMed:22379140, PubMed:26094711). Highly expressed during the sexual blood stage (PubMed:12543146).
In schizonts, may be phosphorylated by PK5; phosphorylation leads to ORC1 dissociation from the telomeres and var gene promoters, translocation to the cytoplasm, where it is degraded by the proteasome.
Leucine heptad repeats are essential for the binding to telomeric DNA.
The C-terminal domain binds ATP and is required for the binding to DNA replication origin sites.
The N-terminal domain binds telomeric DNA and is required for the silencing of telomers and var genes.
Belongs to the universal ribosomal protein uS8 family.
Component of the 7-subunit TFIIH core complex.
In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape.
Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.
Plays a role in the recruitment of the exosome to pre-rRNA to mediate the 3'-5' end processing of the 5.8S rRNA.
Belongs to the PI3/PI4-kinase family. Type II PI4K subfamily.
Belongs to the V-ATPase e1/e2 subunit family.
Belongs to the CDP-alcohol phosphatidyltransferase class-II family.
Functions in the biosynthesis of the anionic phospholipids phosphatidylglycerol and cardiolipin.
Belongs to the eukaryotic ribosomal protein eL20 family.
Belongs to the casein kinase 2 subunit beta family.
Tetramer of two alpha and two beta subunits.
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
In the C-terminal section; belongs to the thymidylate synthase family.
In the N-terminal section; belongs to the dihydrofolate reductase family.
Belongs to the WD repeat DCAF13/WDSOF1 family.
May be involved in the degradation of misfolded endoplasmic reticulum (ER) luminal proteins.
Belongs to the universal ribosomal protein uL16 family.
Belongs to the universal ribosomal protein uS15 family.
Belongs to the eukaryotic ribosomal protein eS12 family.
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (Probable). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (Probable). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (Probable). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (Probable).
Component of the small ribosomal subunit (PubMed:24913268, PubMed:26432834). Mature ribosomes consist of a small (40S) and a large (60S) subunit (PubMed:24913268, PubMed:26432834). The 40S subunit contains about 32 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 42 different proteins and 3 molecules of RNA (28S, 5.8S and 5S) (PubMed:24913268, PubMed:26432834).
Expressed during the asexual blood stage (at protein level).
May be involved in fusion of retrograde transport vesicles derived from an endocytic compartment with the Golgi complex.
Belongs to the prefoldin subunit beta family.
Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins (By similarity).
Belongs to the phenylalanyl-tRNA synthetase beta subunit family. Type 2 subfamily.
In the mitochondrion and together with LipL1, involved in the lipoylation of the E2 component of the branched chain alpha-ketoacid dehydrogenase complex BCKDH-E2/BCDH and the E2 component of the alpha -ketoglutarate dehydrogenase complex KDH (PubMed:25116855). LipL1 is responsible for catalysing the activation of lipoate, forming lipoyl-AMP while LipL2 is required but is not capable of catalyzing this reaction (PubMed:25116855). Although its role is unclear, it may catalyze the transfer of lipoyl groups from lipoyl-AMP to BCDH and KDH or act as an effector protein (PubMed:25116855).
Lacks lipoate-protein ligase activity, probably due the loss of the lysine residue involved in the formation of the lipoyl-AMP reaction intermediate (PubMed:25116855). However, in some studies appears to be able to partially rescue ligase activity in E.coli lacking ligases lplA and lipB (PubMed:17244193, PubMed:18069893).
Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP synthases family.
Belongs to the succinate/malate CoA ligase beta subunit family.
Heterodimer of an alpha and a beta subunit.
Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.
Involved in pre-mRNA splicing (By similarity). Binds RNA (By similarity).
Probable component of the spliceosome C complex.
The C-terminal RRM domain and the zinc finger motif are necessary for RNA-binding.
Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.
Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.
Interacts with PCNA1 and PCNA2 (PubMed:26251451). Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity.
Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma.
Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
Belongs to the eukaryotic ribosomal protein eL43 family.
Component of the large ribosomal subunit (PubMed:24913268, PubMed:26432834, PubMed:28288098). Mature ribosomes consist of a small (40S) and a large (60S) subunit (PubMed:24913268, PubMed:26432834). The 40S subunit contains about 32 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 42 different proteins and 3 molecules of RNA (28S, 5.8S and 5S) (PubMed:24913268, PubMed:26432834).
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:28288098). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (Probable). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (Probable). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (Probable).
Belongs to the eukaryotic ribosomal protein eL6 family.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type 2 subfamily.
Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis.
Belongs to the V-ATPase G subunit family.
Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.
Belongs to the prokaryotic/mitochondrial release factor family.
Binds specifically to the 3'-terminal U-tract of U6 snRNA.
Dimer of alpha and beta chains (Probable). A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells (Probable). Interacts with DCX/apicortin; the interaction stabilizes microtubule assembly (PubMed:33633135).
Expressed during the parasite blood stage, including in trophozoites, schizonts and free merozoites (at protein level).
Tamoxifen used to treat breast cancer blocks the interaction between apicortin and, alpha-tubulin 1 and beta-tubulin resulting in microtubule destabilization.
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:33633135). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
Seems to be required for maximal rate of protein biosynthesis. Enhances ribosome dissociation into subunits and stabilizes the binding of the initiator Met-tRNA(I) to 40 S ribosomal subunits.
Belongs to the aerobic coproporphyrinogen-III oxidase family.
Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
Belongs to the SOS response-associated peptidase family.
Acts as a specific inhibitor of subtilisin-like protease SUB1.
Belongs to the eukaryotic ribosomal protein P1/P2 family.
P1 and P2 exist as dimers at the large ribosomal subunit.
Plays an important role in the elongation step of protein synthesis.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.
Belongs to the eukaryotic ribosomal protein eS21 family.
May be involved in protein traffic between late Golgi and early endosomes.
Binds 2 Mg(2+) ions per subunit (PubMed:25787157). Mg(2+) is required for catalysis and for stabilizing the dimer (PubMed:25787157). Unlike for mammalian and yeast enolases, Mg(2+) is dispensable to form an active closed conformation (PubMed:25787157). Inhibited by high levels of Mg(2+) (By similarity).
During the asexual blood stage, expressed in rings, trophozoites, schizonts and merozoites (at protein level).
Glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:19268421, PubMed:25787157). In addition to glycolysis, involved in various processes such as parasite development and invasion (By similarity). Plays an essential role during ookinete invasion of the mosquito vector midgut by mediating the interaction of the ookinete with the midgut epithelium and, further, by binding to mammalian host plasminogen in the blood meal, whose conversion to active plasmin promotes the invasion process (By similarity).
Homodimer (PubMed:19268421, PubMed:25787157). Forms a complex at least composed of DegP, ENO and HSP70 (PubMed:24494818). Interacts with G-actin (PubMed:19642995). Interacts (via the DKSLVK motif) with mammalian host PLG/plasminogen (present in the mosquito blood meal); the interaction occurs at the ookinete cell surface and is required for ookinete invasion of the mosquito midgut (PubMed:19642995). Interacts with A.gambiae EBP; depending on the Plasmodium species, the interaction is either involved in ookinete invasion of the mosquito midgut (P.berghei) or is dispensable (P.falciparum) (By similarity).
The DKSLVK motif binds to the lysine-binding Kringle domains of plasminogen from various mammalian species (By similarity). This motif is present only in enolases of plant and several microbial pathogens including Plasmodium species (By similarity).
The pentapeptide insert motif is required for the stabilization of the apo-enzyme in an active closed conformation, independently of Mg(2+) binding (PubMed:19268421, PubMed:25787157). The motif is also required for homodimerization (PubMed:19268421, PubMed:25787157). This motif is only present in Apicomplexa and plant enolases (Probable).
Belongs to the peroxiredoxin family. Prx5 subfamily.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides.
Belongs to the autoinducer-2 exporter (AI-2E) (TC 2.A.86) family.
Expressed during the parasite blood stage, including in rings, trophozoites, schizonts and merozoites (at protein level).
Monomer (PubMed:25475729). Component of the Plasmodium translocon of exported proteins (PTEX) complex composed of HSP101, EXP2, PTEX150, PTEX88 and TRX2 (PubMed:19536257).
Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:16910770, PubMed:22355694). As part of the translocon PTEX complex, plays a role in the export of parasite proteins into the host erythrocyte (By similarity). The translocon PTEX complex is a multi-protein machinery resident in the parasite parasitophorous vacuolar membrane, responsible for protein secretion into host cells (PubMed:19536257). May contribute to the unfolding of proteins containing the PEXEL localization motif before their passage through the translocon or regulate the PTEX complex function (PubMed:19536257).
The disulfide bond between Cys-82 and Cys-85 acts as a redox-active center and is reduced by thioredoxin reductase TRXR.
Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.
Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
By heat and oxidative stresses in trophozoites and schizonts (at protein level).
During the asexual blood stage, expressed in trophozoites, schizonts and free merozoites (at protein level).
Oligomer; may form trimers or hexamers (PubMed:24494818). Forms a complex at least composed of DegP, ENO and HSP70 (PubMed:24494818).
Serine protease which also acts as a protein chaperone (PubMed:24494818). Plays a role in the parasite development in host erythrocytes possibly by protecting it against thermal and oxidative stresses (PubMed:24494818).
The PDZ domain is dispensable for protease and chaperone activities.
Belongs to the U1 small nuclear ribonucleoprotein C family.
Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.
U1 snRNP is composed of the 7 core Sm proteins B/B', D1, D2, D3, E, F and G that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least 3 U1 snRNP-specific proteins U1-70K, U1-A and U1-C. U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA.
Belongs to the universal ribosomal protein uS10 family.
Belongs to the damage-control phosphatase family. Sugar phosphate phosphatase III subfamily.
Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate. Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism.
Subfamily III proteins have a conserved RTxK motif about 40-50 residues from the C-terminus; the threonine may be replaced by serine or cysteine.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Component of the conserved oligomeric Golgi complex.
During the asexual blood stage, catalyzes the initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation; specifically cleaves between Phe-33 and Leu-34 of Hb alpha-chain. Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity.
Inhibited by KNI derived compounds KNI-10333 and to a lesser extent KNI-10743.
No growth defect (PubMed:15513918). However, slight decrease in proliferation and slight increase in doubling time during the asexual blood stage in an amino acid-limited medium (PubMed:15513918).
Proteolytically cleaved into the soluble active mature form in the digestive vacuole by cysteine protease falcipains; the process begins at the early ring stage (PubMed:14709539). Proteolysis requires an acidic environment (By similarity).
Involved in the second step of GPI biosynthesis. De-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol.
Belongs to the eukaryotic ribosomal protein eL24 family.
Belongs to the deoxyhypusine hydroxylase family.
Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate to form hypusine, an essential post-translational modification only found in mature eIF-5A factor.
Belongs to the class IV-like SAM-binding methyltransferase superfamily.
Belongs to the eukaryotic ribosomal protein eL38 family.
Blood stage parasites are not viable (PubMed:18083098, PubMed:29459732). Initial schizont development is normal but merozoite egress is abolished due to a failure to rupture the parasitophorous vacuole membrane (PubMed:29459732).
Heterodimer between p54 form and propeptide p31; the interaction inhibits p54 catalytic activity.
Serine protease which plays an essential role in merozoite invasion of and egress from host erythrocytes by processing and activating various merozoite surface and parasitophorous vacuole proteins (PubMed:18083098, PubMed:19214190, PubMed:21220481, PubMed:29459732). Mediates the proteolytic maturation of serine proteases SERA4, SERA5 and SERA6 just prior to merozoite egress (PubMed:18083098, PubMed:19214190, PubMed:29459732). Prior to merozoite egress, cleaves merozoite surface proteins MSP1, MSP6 and MSP7, which form the MSP1/6/7 complex, and thereby may prime the parasite cell surface for invasion of fresh erythrocytes (PubMed:19214190, PubMed:29459732). Prior to merozoite egress, cleaves MSRP2 converting it to MSRP2 p25 form, and RAP1 converting it to RAP1 p67 form (PubMed:21220481).
The disulfide bond between Cys-521 and Cys-534 acts as a redox-sensitive disulfide switch. The oxidized form is required for catalytic activity.
The propeptide (p31) is cleaved, probably by autocatalysis, during the transport to or in the Golgi apparatus, and remains non-covalently associated with the p54 form as an inhibitor. p54 is further cleaved into the p45 form (By similarity). This cleavage is likely occurring in the exoneme prior to egress and is mediated by PMX/plasmepsin X (PubMed:32109369).
The relevance of the N-glycosylation is not clear. In an insect expression system, SUB1 glycosylation appears to affect its processing into the active mature form suggesting that SUB1 may not be N-glycosylated in parasites.
p54 and probably p47 forms are inhibited by the non-covalent interaction with the cleaved propeptide (PubMed:19214190). Inhibited by subtilisin propeptide-like protein SUB1-ProM (PubMed:31942933). Inhibited by small molecule MRT12113 (PubMed:18083098).
Belongs to the archaeal Rpo12/eukaryotic RPC10 RNA polymerase subunit family.
Belongs to the uracil-DNA glycosylase (UDG) superfamily. UNG family.
Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Belongs to the eukaryotic ribosomal protein eL33 family.
Belongs to the acetyltransferase family. MAK3 subfamily.
Belongs to the eukaryotic ribosomal protein eS19 family.
Belongs to the replication factor A protein 3 family.
Catalytic component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (PubMed:18054093, PubMed:30127496). Specifically cleaves N-terminal signal peptides that contain a hydrophobic alpha-helix (h-region) shorter than 18-20 amino acids (By similarity).
Causes a reduction in parasite growth in the host erythrocyte (PubMed:30127496, PubMed:18054093). Reduces levels of the mature form of SERA5 but not of PEXEL-containing proteins (PubMed:30127496).
Component of the signal peptidase complex (SPC) composed of a catalytic subunit SEC11/SPC21 and three accessory subunits SPC25, SPC3/SPC22, SPC1/SPC12 (PubMed:30127496). Within the complex, interacts with SPC25 (PubMed:30127496). The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates (By similarity). This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids (By similarity). The complex interacts with the SEC61 channel-forming translocon complex and is involved in the import of classical signal sequence-containing proteins (PubMed:30127496).
Expressed during the asexual blood stage, including ring, trophozoite and schizont stages (at protein level).
Phosphorylated (PubMed:18054093). Phosphorylation increases catalytic activity (PubMed:18054093).
Phosphorylation increases catalytic activity (PubMed:18054093). Ca(2+) slightly increases catalytic activity in vitro (PubMed:18054093).
The C-terminal short (CTS) helix is essential for catalytic activity (By similarity). It may be accommodated as a transmembrane helix in the thinned membrane environment of the complex, similarly to the signal peptide in the complex substrates (By similarity).
Addition of antibodies against PIMMS43 to the infectious blood meal significantly reduces transmission of malaria parasites by A.coluzzii mosquitoes.
Analysis of single nucleotide polymorphisms revealed significant population differentiation, mostly between populations of some West or Central and East African countries (PubMed:32165544). Differences in PIMMS43 may represent an adaptation of African malaria parasite populations for transmission by different mosquito vectors that are also differentially distributed across the continent (PubMed:32165544).
Expressed in female gametes, early-stage zygotes, ookinetes and sporozoites found in the mosquito salivary gland lumen (at protein level) (PubMed:32165544). Not detected in in vitro-cultured asexual blood stage or gametocytes (at protein level) (PubMed:32165544). Transcription begins in gametocytes and peaks in zygotes and ookinetes. Expression declines in oocysts but reappears in sporozoites from mosquito salivary glands (PubMed:32165544). Not detected in in vitro-cultured asexual blood stage parasites (PubMed:32165544).
Involved in ookinete evasion of the mosquito complement-like response, oocyst maturation, sporozoite development and infectivity.
Monomer (PubMed:32165544). May form multimers with an unknown protein(s) (By similarity).
Catalytic component of the tRNA-splicing ligase complex.
Catalytic subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester. May act as an RNA ligase with broad substrate specificity, and may function toward other RNAs.
Ligation probably proceeds through 3 nucleotidyl transfer steps, with 2',3'-cyclic phosphate termini being hydrolyzed to 3'-P termini in a step that precedes 3'-P activation with GMP. In the first nucleotidyl transfer step, RTCB reacts with GTP to form a covalent RTCB-histidine-GMP intermediate with release of PPi; in the second step, the GMP moiety is transferred to the RNA 3'-P; in the third step, the 5'-OH from the opposite RNA strand attacks the activated 3'-P to form a 3',5'-phosphodiester bond and release GMP.
Belongs to the U2 small nuclear ribonucleoprotein A family.
Converts protoheme IX and farnesyl diphosphate to heme O.
Belongs to the polypeptide deformylase family.
Removes the formyl group from the N-terminal Met of newly synthesized proteins.
Belongs to the SWEET sugar transporter family.
Belongs to the 6-phosphogluconate dehydrogenase family.
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Belongs to the archaeal rpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.
Belongs to the ATPase delta chain family.
Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX.
Small GTPase required for proper nuclear import of RNA polymerase II and III (RNAPII and RNAPIII). May act at an RNAP assembly step prior to nuclear import.
Component of the retromer complex, composed of VPS26, VPS29 and VPS35 (PubMed:29654975). As part of the retromer complex, interacts with the sorting receptor SORTLR/sortilin (PubMed:29654975). Interacts with GTPase RAB7 (PubMed:32512169).
Plays a role in vesicular protein sorting (By similarity). Component of the membrane-associated retromer complex which is essential in endosome-to-Golgi retrograde transport (By similarity).
Component of a complex composed of SPC25 and PMV; the interaction is mediated via the transmembrane domains (PubMed:30127496). The complex interacts with the SEC61 channel-forming translocon complex and is involved in the recognition and import of PEXEL motif-containing proteins into the ER for subsequent export (PubMed:30127496).
During the asexual blood stage, plays an essential role in the export of several proteins into the host erythrocytes by cleaving the pentameric localization motif RxLxE/Q/D (termed Plasmodium export element (PEXEL)) located downstream of the N-terminal secretory signal sequence (PubMed:20130643, PubMed:20130644, PubMed:24983235, PubMed:30127496, PubMed:30517136). Specifically, cleaves after the leucine residue in the RxLxE/Q/D (or RxLxxE) motif of exported proteins including RESA, EMP2, EMP3, KAHRP, RIF/Rifin and STEVOR (PubMed:20130643, PubMed:20130644, PubMed:23387285, PubMed:25447707, PubMed:25986559, PubMed:24983235). Also, by regulating protein export, plays an essential role in gametocyte development and thus, parasite transmission to the mosquito vector (By similarity).
Expressed during the asexual blood stage; expression is low at the ring stage and then increases through the trophozoite and schizont stages (at protein level).
Inhibited by peptidomimetic inhibitor WEHI-842 (PubMed:26214367). Inhibited by Cu(2+) and Hg(2+) (PubMed:25447707).
It is not clear if the zymogen has a cleavable propeptide (PubMed:25447707). In vitro, appears to be cleaved between Asn-80 and Ala-81 (PubMed:25447707). Cleavage of the putative propeptide is dispensable for catalytic activity (PubMed:25447707, PubMed:25986559).
It is unclear if PMV is glycosylated as other members of the same enzyme family, ie. PMI and PMII, are not.
The transmembrane domain is essential for localization to the endoplasmic reticulum.
Belongs to the WD repeat BOP1/ERB1 family.
Belongs to the CRT-like transporter family.
Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.
Belongs to the OMP decarboxylase family. Type 2 subfamily.
Belongs to the universal ribosomal protein uL1 family.
Belongs to the tRNA-intron endonuclease family.
Belongs to the eukaryotic ribosomal protein eS27 family.
Belongs to the reverse transcriptase family. Telomerase subfamily.
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. It elongates telomeres. It is a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme.
Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
Belongs to the class-I aminoacyl-tRNA synthetase family. Glutamate--tRNA ligase type 1 subfamily.
Catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu).
Required for replication-independent chromatin assembly and for the periodic repression of histone gene transcription during the cell cycle.
Component of the ER membrane protein complex (EMC).
Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins.
Dimerization causes loss of catalytic activity (PubMed:20435072). Inhibited by pepstatin A (PubMed:16624575). Inhibited by Zn(2+) (PubMed:20435072).
During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) or globins (PubMed:16624575). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).
Expressed during the asexual blood stage; expression begins in trophozoites and continues in schizonts (at protein level).
It is unclear if PMIII is glycosylated as other members of the same enzyme family, ie. PMI and PMII, are not.
No growth defect (PubMed:15513918). However, slight decrease in proliferation and slight increase in doubling time during the asexual blood stage in an amino acid-limited medium (PubMed:15513918). Triple knockout of PMI, PMII and PMIII causes a slight decrease in proliferation during the asexual blood stage in an amino acid-limited medium (PubMed:17581121). Quadruple knockout of PMI, PMII, PMIII and PMIV causes a decrease in proliferation, an impaired proliferation in an amino acid-limited medium, a reduced formation of haemozoin and an abnormal accumulation of endosomal vesicles inside the digestive vacuole (PubMed:17581121).
Probable homodimer; in the zymogen form (Probable). Monomer; in the active form (PubMed:20435072). Acidification disrupts homodimerization (By similarity). Component of the hemozoin formation complex (HFC) composed of falcipain 2, plasmepsins PMII, PMIII/HAP and PMIV, heme detoxifying protein HDP and falcilysin FLN (PubMed:23471987). The HFC complex is involved in hemoglobin degradation and detoxification of heme in the food vacuole during the asexual blood stage (PubMed:23471987).
Proteolytically cleaved into the soluble active mature form by cysteine proteases in the digestive vacuole of trophozoites (By similarity). Proteolysis requires an acidic environment (By similarity). Transprocessing may serve as an alternate activation system (PubMed:18312598).
Unlike other plasmepsins, one of the two catalytic aspartates, Asp-157, is replaced with histidine; however, the protein is catalytic active (PubMed:16624575). Unlikely to act as a serine protease (PubMed:18312598). His-157 may stabilizes the catalysis and Asp-337 may act as both an acid and a base during catalysis.
Belongs to the PPP phosphatase family. BSU subfamily.
Belongs to the eukaryotic ribosomal protein eL36 family.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.
Calcium-selective channel required to prevent calcium stores from overfilling.
Belongs to the eukaryotic ribosomal protein eL41 family.
Component of the large ribosomal subunit.
Belongs to the Mrp/NBP35 ATP-binding proteins family.
Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to cysteines occuring in specific C-terminal amino acid sequences.
Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.
Belongs to the small GTPase superfamily. Ran family.
GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle.
Activated by Co(2+) (PubMed:17720817, PubMed:22709581). Inhibited by high concentrations (>1mM) of Zn(2+) (PubMed:22709581).
Aminopeptidase which specifically catalyzes the removal of glutamic acid or aspartic acid residues from the N-terminus of peptides (PubMed:17720817, PubMed:17895246, PubMed:22709581). May play a role in the final step of host hemoglobin catabolism, by cleaving hemoglobin-derived oligopeptides in the cytoplasm (Probable).
Expressed during the asexual blood stage including in rings, trophozoites and schizonts (at protein level).
Homododecamer composed of homodimers and homotrimers that assemble into a tetrahedron shape to create a central tunnel containing the active sites (PubMed:22709581). Homooctamer (PubMed:17720817).
RNAi-mediated knockdown causes a loss in aspartyl aminopeptidase activity, the rupture of the food vacuole in ring and schizonts and an accumulation of large lipid droplets and host hemoglobin in trophozoites.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family.
In P.berghei, dispensable for male gamete attachment to erythrocytes and the formation of exflagellation centers.
Plays an essential role in male gamete fertility (By similarity). Required for the binding to erythrocytes and thus, for the formation of exflagellation centers (By similarity).
Specifically presents on the surface of stage V male gametocytes (at protein level) (PubMed:12106866, PubMed:30297725). Not expressed in gametes or asexual parasites (PubMed:12106866). Expression peaks in stage III/IV gametocytes, then sharply declines in gametes (PubMed:12106866).
At the asexual blood stage, causes Maurer's cleft swelling and fragmentation, aberrant knob formation, with fewer and enlarged knobs, defective PfEMP1 trafficking characterized by impaired EMP1 surface expression and EMP1 accumulation at Maurer's clefts and a loss of adhesion of host infected erythrocytes to endothelial cell ligands (PubMed:32184257). Infected erythrocytes have decreased cellular rigidity and increased osmotic fragility (PubMed:32184257). Parasite growth is faster (PubMed:32184257).
During the asexual blood stage and probably at the ring/trophozoite stages, plays a role in Maurer's cleft formation and/or morphology (PubMed:32184257). Also, involved in the loading of the virulence factor EMP1 into the Maurer's cleft membrane (PubMed:32184257). By binding to host chemokine CX3CL1, mediates the cytoadherence of host erythrocytes infected with parasite mature forms (late trophozoite and schizont) to endothelial cells, which sequesters them away from the circulation and thus prevents their elimination by the host spleen (PubMed:27653778).
Expressed during the asexual blood stage in late rings, trophozoites and schizonts (at protein level) (PubMed:27653778, PubMed:24983235, PubMed:32184257). Expressed in gametocytes (at protein level) (PubMed:27653778).
Monomer (PubMed:27653778, PubMed:31356937). May form (via the first cytoplasmic domain) homodimers or homotrimers; disulfide-linked (PubMed:27653778, PubMed:31356937). Interacts with MAHRP1 (PubMed:32184257). May interact (via first cytoplasmic domain) with SBP1; the interaction is likely to occur at the ring stage in the Maurer's clefts and is weaken by ATP (PubMed:31356937). Interacts (via extracellular domain) with human chemokine CX3CL1; the interaction mediates the adhesion of infected erythrocytes with endothelial cells (PubMed:27653778).
Potential vaccine candidate as CBP2-based peptides or antibodies against CBP2 prevent adhesion of infected erythrocytes to endothelial cells.
The first cytoplasmic domain binds ATP and nucleic acids such as RNA and DNA in vitro.
Belongs to the metallophosphoesterase superfamily. Purple acid phosphatase family.
Binds 2 metal cations (PubMed:22387043). The role of the metal cation is unclear (PubMed:22387043).
Component of the glideosome complex composed of GAP50, GAP45, MTIP and MyoA; the complex is formed during the late schizont stage and in merozoites (PubMed:16321976, PubMed:16513191, PubMed:16750579, PubMed:19576251, PubMed:21239623). MyoA, MTIP and GAP45 probably form an initial complex in the cytoplasm which is then recruited to the outer face of the inner membrane complex via the interaction with GAP50 (PubMed:16750579). Interacts with GAP45; the interaction is independent of GAP45 phosphorylation status and can also occur independently of the formation of the glideosome complex (PubMed:19576251). Interacts with human factor H isoform CFH (via sushi 6-7 domains) and isoform FHL-1 (via sushi 6-7 domains); the interaction occurs in the vector mosquito midgut at the surface of activated gametocytes; the interaction protects the parasite from alternative complement pathway-mediated elimination (PubMed:23332154).
Component of the glideosome complex, an inner membrane complex structure involved in parasite gliding motility and host cell invasion (PubMed:16321976, PubMed:16513191, PubMed:16750579, PubMed:19576251). During the asexual blood stage, may play a role in the assembly and anchoring of the glideosome complex to the inner membrane complex (PubMed:16750579). During the sexual stage in the vector mosquito midgut, protects gametocytes against host alternative complement pathway-mediated elimination by interacting with host complement inhibitor factor H (PubMed:23332154). Has phosphatase activity towards nucleotides such as ATP, vitamins B1 and B6, phosphorylated sugars, glycerol phosphates and inositol triphosphates (PubMed:20070315). However, the phosphatase activity is controversial (PubMed:22387043).
Expressed during the asexual blood stage; expression begins in rings and peaks in schizonts and merozoites (at protein level) (PubMed:16321976, PubMed:16513191, PubMed:16750579, PubMed:19576251, PubMed:20070315, PubMed:21239623, PubMed:23332154). Expressed in gametocytes (at protein level) (PubMed:23332154). Expressed in the zygote at the early stages (at protein level) (PubMed:23332154).
The C-terminal transmembrane and cytoplasmic domains are required for the trafficking of the protein to the inner membrane complex.
The N-terminus signal is likely to be cleaved.
The phosphatase activity appears to be controversial (PubMed:20070315, PubMed:22387043). The active site residues are not conserved (PubMed:22387043). One study shows that there is no phosphatase activity towards synthetic substrate pNPP (PubMed:22387043). However, another study shows a broad specificity towards organic phosphoester substrates (PubMed:20070315).
Acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP (By similarity).
Belongs to the dynein heavy chain family.
Consists of at least two heavy chains and a number of intermediate and light chains.
Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.
Belongs to the DNA polymerase delta/II small subunit family.
Belongs to the pyrroline-5-carboxylate reductase family.
Belongs to the RecA family. DMC1 subfamily.
Belongs to the pseudouridine synthase TruB family.
Component of the 60S subunit of the ribosome.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.
Autophosphorylates in presence of cyclin cyc-1 but not in presence of cyclin cyc-3.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
Expressed during the asexual blood stage; expression is low at the ring stage and peaks in trophozoites and schizonts (at protein level).
May form a complex composed of at least the catalytic subunit CRK2 and a cyclin.
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-158 activates it (By similarity). Activated by cyclin cyc-1 in vitro (PubMed:10722743, PubMed:12869562). Activated by cyclin cyc-3 in vitro (PubMed:12869562).
Serine/threonine-protein kinase (PubMed:10722743, PubMed:12869562, PubMed:26094711). Involved in the control of the cell cycle (By similarity). Required for entry into S-phase and mitosis (By similarity). Probable component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II (PubMed:12869562). In schizonts, phosphorylates ORC1 resulting in its dissociation from DNA, relocalization to the cytoplasm and likely its degradation (PubMed:26094711).
Belongs to the eukaryotic/archaeal RNase P protein component 3 family.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.
Down-regulated at the ring stage by melatonin.
Expressed during the asexual blood stage, including rings, trophozoites and schizonts.
In blood stage parasites, phosphorylates translation factor eIF2alpha in response to amino acid starvation (PubMed:19435497, PubMed:29241041). During the asexual blood stage, involved in the response to the host hormone melatonin which is used by the parasite to modulate its cell cycle (PubMed:32702775).
No defect in erythrocyte asexual growth and gametocytogenesis (PubMed:19435497). No defect in the production of sporozoites in the mosquito vector (PubMed:19435497). In blood stage parasites, phosphorylation of eIF2alpha in response to amino-acid starvation is impaired (PubMed:19435497). During the asexual blood stage, increased in parasitemia induced by host melatonin is impaired (PubMed:32702775).
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
Expressed in gametocytes; expression starts in young gametocytes (30-40h post-invasion of host erythrocytes) (at protein level).
Involved in male gametogenesis (PubMed:14698439). Required for exflagellation of male gametocytes (PubMed:14698439). May play a role in parasite transmission in the mosquito (By similarity). Binds to the mosquito vector midgut (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. MenG/UbiE family.
Component of a multi-subunit COQ enzyme complex.
Methyltransferase required for the conversion of 2-polyprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2).
Belongs to the pterin-4-alpha-carbinolamine dehydratase family.
Belongs to the eukaryotic ATPase epsilon family.
Binds to apicoplast RNA transcripts, preferentially to the motif UUAU, and protects RNA transcripts from degradation by ribonuclease.
Belongs to the methyltransferase superfamily. RsmH family.
Component of the oligosaccharyltransferase (OST) complex.
Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity.
Belongs to the peptidase T1B family. HslV subfamily.
Common component of the spliceosome and rRNA processing machinery.
Essential component of the cytosolic iron-sulfur (Fe/S) protein assembly machinery. Required for the maturation of extramitochondrial Fe/S proteins.
Belongs to the AAA ATPase family. BCS1 subfamily.
Belongs to the CSN7/EIF3M family. CSN7 subfamily.
Belongs to the bacterial ribosomal protein bL28 family.
Belongs to the Nudix hydrolase family. DCP2 subfamily.
Divalent metal ions. Mg(2+) is the most effective.
Belongs to the mitochondrion-specific ribosomal protein mL49 family.
Expressed during the asexual blood stage, probably in gametocytes.
Impaired gametogenesis (PubMed:18452584). Gametocytes are morphologically normal up to and including stage V of development; however, gametocytes fail to round up upon stimulation of gametogenesis with xanthurenic acid and levels of exflagellation are severely reduced (PubMed:18452584). Higher levels of intracellular cGMP in stages III to V gametocytes (PubMed:18452584).
Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes (PubMed:18452584). Probably by regulating cGMP levels, required for activation of gametogenesis (PubMed:18452584).
Belongs to the universal ribosomal protein uS3 family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family.
Belongs to the Mediator complex subunit 7 family.
Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery.
Belongs to the DNA mismatch repair MutL/HexB family.
During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) (By similarity). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).
It is unclear if PMIV is glycosylated as other members of the same enzyme family, ie. PMI and PMII, are not.
Proteolytically cleaved into the soluble active mature form by cysteine proteases in the digestive vacuole of trophozoites. Proteolysis requires an acidic environment. Autoprocessing or transprocessing by other plasmepsins such as PMII may serve as an alternate activation system.
Quadruple knockout of PMI, PMII, PMIII and PMIV causes a decrease in proliferation, an impaired proliferation in an amino acid-limited medium, a reduced formation of haemozoin and an abnormal accumulation of endosomal vesicles inside the digestive vacuole.
Does not have erythrocyte-receptor-binding ability.
Heterodimer; heterodimerizes with PF12. May form an antiparallel heterodimer with PF12.
No visible phenotype. Parasites grow at normal rates in vitro.
Specifically present in asexual blood stage parasites. First detected in the trophozoite stage, 30-40 hours post-invasion (HPI) and the proteins reaches peak expression in schizont stage, 40-48 HPI.
The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).
Dissociation from BIP and oligomerization, may results autophosphorylation and kinase activity induction.
During the asexual blood stage, phosphorylates translation factor eIF2alpha in late schizonts resulting in protein translation inhibition (PubMed:22355110, PubMed:29241041). Plays a role in trophozoite differentiation into schizonts (PubMed:29241041).
May form oligomers in response to stress; oligomerization may result in catalytic activity (PubMed:29241041). Interacts with BIP; the interaction is disrupted in response to stress (By similarity).
Smaller forms of 80-90kDa appear to be present in the asexual blood stage suggesting that the protein may be proteolytically cleaved (By similarity). They localize to the cytoplasm in schizonts, to organelles in all blood stages and to the host erythrocyte membrane during schizont segmentation (By similarity).
Belongs to the pyridoxine kinase family.
Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.
A truncated form of MSP9 has serine protease activity in vitro; however, it is not clear if this is physiologically relevant (PubMed:10699251). Also, the putative residues forming the catalytic triad (His-55, Asp-94, and Ser-190) are not conserved in P.vivax, P.knowlesi, and P.cynomolgi orthologs casting a doubt on the physiological relevance of the protease activity (PubMed:14630931).
During the asexual blood stage, involved in the sialic acid-independent (SAID) merozoite invasion of host erythrocytes by binding to host SLC4A1/Band 3 protein on the surface of the host erythrocyte.
Expressed during the asexual blood stage, including in merozoites (at protein level).
Interacts with MSP1 19kDa (MSP1p19) and 42kDa (MSP1p42) proteolytic products; the interaction is direct (PubMed:14630931, PubMed:16289042). Interacts with host SLC4A1/Band 3 protein (via the 5ABC region) (PubMed:14630931). MSP1p19 or MSP1p42 and MSP9 form a co-ligand complex that interacts with host SLC4A1/Band 3 protein (PubMed:14630931, PubMed:16289042).
Belongs to the aconitase/IPM isomerase family.
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family.
Belongs to the eukaryotic diacylglycerol kinase family.
Belongs to the ferredoxin--NADP reductase type 1 family.
May play a role in the terminal step of the DOXP/MEP pathway for isoprenoid precursor biosynthesis.
Monomer (PubMed:17258767). Homodimer; disulfide linked (PubMed:17258767, PubMed:19736991). NADP binding accelerates formation of an inactive, disulfide-linked homodimer when the protein is exposed to air for 24 hours or more (in vitro); the physiological relevance of this is uncertain (PubMed:17258767).
Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
Dual specificity protein phosphatase which dephosphorylates both phosphotyrosine and phosphoserine residues.
Expressed during the parasite blood stage, including in rings, trophozoites and schizonts (at protein level) (PubMed:14698441). Expressed in gametocytes (at protein level) (PubMed:14698441).
Belongs to the peptidase M24 family. SPT16 subfamily.
Belongs to the phosphoglycerate kinase family.
Belongs to the RNA methyltransferase RsmE family.
Specifically methylates the N3 position of the uracil ring of uridine 1498 (m3U1498) in 16S rRNA. Acts on the fully assembled 30S ribosomal subunit.
ACT1 and ACT2 differ in their polymerization, filament stability and helical structure. Unlike mammalian actin, Apicomplexa actins do not form long and stable filaments.
ATP hydrolysis occurs in the polymeric state. Unlike for mammalian actin, ATP hydrolysis occurs also in the monomeric form and the release of inorganic phosphate (Pi) is more efficient.
Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm. Polymerizes into longer and more stable actin filaments compared to ACT1/actin-1. Has ATPase activity. ATP hydrolysis leads to the formation of a stable intermediate ADP-inorganic phosphate (Pi) actin, which is followed by the release of Pi. ATP hydrolysis affects filament stability; ADP-bound actin depolymerizes much faster than ATP- or ADP-Pi-bound actin. Plays an essential role in male gametocyte development in the mosquito midgut, functioning in several processes including male gametocyte egress from host erythrocytes, formation of a beating flagellum and relocalization of ACT1/actin-1 to the cytoplasm. On the basal side of the mosquito midgut epithelium, required for the development of ookinetes into sporogonic oocysts.
Monomer (G-actin). Oligomer (F-actin). Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Unlike for mammalian monomeric actin, monomeric actin is able to induce oligomerization with ATP or ADP. Mg(2+), which is used to coordinate ATP, is required for polymerization.
Necessary for the splicing of pre-mRNA. Has a role in the recognition of the branch site (5'-UACUAAC-3'), the pyrimidine tract and the 3'-splice site at the 3'-end of introns.
Belongs to the glycosyltransferase 4 family.
Mitochondrial inner membrane magnesium transporter required for mitochondrial magnesium homeostasis (By similarity). Involved in the development of the sporozoite in the mosquito vector midgut (By similarity).
Belongs to the V-ATPase F subunit family.
Belongs to the protein disulfide isomerase family.
Belongs to the glycosyltransferase 22 family.
Expressed throughout the erythrocytic development of the infected host, low expression in rings and schizonts, high levels in trophozoites.
Transcriptional activator. Has a role in the parasite erythrocytic cycle where it directly regulates key genes involved in cell cycle regulation and progression. Binds directly to Myb regulatory elements.
dsRNA causes reduced expression, alters parasite growth and trophozoite to schizont transition during the erythrocytic cycle.
Belongs to the fatty acid desaturase type 1 family.
The histidine box domains are involved in binding the catalytic metal ions.
Belongs to the GTP cyclohydrolase I family.
Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
Belongs to the WD repeat PRL1/PRL2 family.
Essential for pre-mRNA splicing. Implicated in the formation of stable, biologically active snRNP structures.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.
Catalyzes the hydrolytic deamination of adenosine to produce inosine (PubMed:19728741, PubMed:31002765). Unlike mammalian adenosine deaminases, also catalyzes the deamination of 5'-methylthioadenosine (MTA), a by-product of polyamine biosynthesis, to produce 5'-methylthioinosine (MTI) (PubMed:19728741, PubMed:31002765). Plays an essential role in the purine salvage pathway which allows the parasite to use host cell purines for the synthesis of nucleic acids (Probable).
Inhibited by coformycin and methylthiocoformycin (MT-coformycin).
Involved in nucleolar processing of pre-18S ribosomal RNA.
Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.
Belongs to the eukaryotic ribosomal protein eL42 family.
Belongs to the universal ribosomal protein uL18 family.
Belongs to the very long-chain fatty acids dehydratase HACD family.
Belongs to the eukaryotic ribosomal protein eL32 family.
Belongs to the ClpX chaperone family. HslU subfamily.
Belongs to the proteasome subunit p55 family.
Belongs to the triosephosphate isomerase family.
Catalyzes the interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate in the glycolytic and gluconeogenic pathways.
Belongs to the helicase family. RAD25/XPB subfamily.
Expressed during the parasite blood stage, including in rings, trophozoites, schizonts and free merozoites (at protein level).
Human microRNA candidate miR-197 and to a lesser extent miR150 causes the down-regulation of apicortin and thus may be a possible candidate for nucleotide-based antimalarial treatment.
Interacts with alpha-tubulin 1 and beta-tubulin; the interaction stabilizes microtubule assembly.
Involved in the stabilization of microtubules (PubMed:33633135). Probably by controlling microtubules stabilization, plays a role in invasion, microneme secretion and parasite growth in host erythrocytes (PubMed:32493727).
Tamoxifen used to treat breast cancer blocks the interaction between DCX/apicortin and, alpha-tubulin 1 and beta-tubulin resulting in microtubule destabilization.
The doublecortin is involved in the binding to microtubules; however, it is not sufficient by itself and requires the partial p25alpha domain.
The partial p25 alpha domain binds to microtubules.
Belongs to the universal ribosomal protein uS13 family.
Belongs to the alpha-ketoglutarate dehydrogenase family.
Acetylated (PubMed:22006844, PubMed:36947546). Exists in both acetylated and unacetylated forms but predominantly in an acetylated form (PubMed:22006844). Deacetylated by Sir2A (PubMed:22006844, PubMed:36947546).
Belongs to the histone-like Alba family.
Expressed during all the asexual blood stages: in the ring form, trophozoites and schizonts (at protein level).
Homodimer (PubMed:22167473). Interacts (acetylated and unacetylated) with Sir2A (PubMed:22006844, PubMed:36947546).
Mild acetylation lowers protein interaction with DNA and high acetylation abolishes DNA-binding activity (PubMed:22006844). DNA binding and endonuclease activity is modulated via deacetylation of Lys-23 by Sir2A (PubMed:36947546, PubMed:22006844). Inhibited in the presence of EDTA and EGTA (PubMed:36947546).
Possesses DNA-binding and endonuclease activities (PubMed:22006844, PubMed:36947546, PubMed:22167473). Binds DNA cooperatively in sequence-independent manner at the DNA minor groove (PubMed:22006844, PubMed:36947546). Exhibits apurinic/apyrimidinic site-driven endonuclease activity (PubMed:36947546). Binds RNA; shows high affinity for poly(A) and a lower affinity for poly(U) templates (PubMed:22167473). In vitro, prevents transcription after DNA binding (PubMed:22006844). Associates with the telomeric region, the subtelomeric TARE6 repeat sequence and the var gene promoters (PubMed:22006844).
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.
Belongs to the eukaryotic ribosomal protein eS4 family.
Involved in autophagic vesicle formation.
Belongs to the ATPase epsilon chain family.
Cysteine protease that cleaves specifically after arginine or lysine residues (PubMed:21858231). May play a role in apoptosis (PubMed:21858231).
Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (PubMed:16750579). Myristoylates adenylate kinase AK2 (By similarity). During the asexual blood stage, may myristoylate proteins such as ARO, CDPK1 and GAP45 (PubMed:16750579, PubMed:34695132). Probably by mediating protein myristoylation, plays a role in the assembly of the inner membrane complex during the early stages of schizogony and in the formation of rhoptries in the late stages and thus merozoite egress (PubMed:34695132).
Heterodimer composed of NMT and AK2; AK2 myristoylation stabilizes the complex.
Belongs to the CND2 (condensin subunit 2) family.
Belongs to the methyltransferase superfamily. RRP8 family.
Probable methyltransferase required to silence rDNA.
Belongs to the Mediator complex subunit 31 family.
Belongs to the bacterial ribosomal protein bL21 family.
Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily.
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Belongs to the eukaryotic ribosomal protein eL13 family.
Belongs to the universal ribosomal protein uS2 family.
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (Probable). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (Probable). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (Probable). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (Probable). Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits (By similarity).
Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
Belongs to the SNF2/RAD54 helicase family.
Binds 1 Mg(2+) ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium (By similarity). Binds magnesium less tightly than zinc (By similarity).
Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium (By similarity). Tightly binds zinc (By similarity).
Expressed at the ring stage during the asexual blood stage.
Knockouts at the asexual blood stage are viable and have normal merozoite formation in the host erythrocytes (PubMed:18590734). cGMP hydrolysis is reduced by about 20% with no effect on cAMP hydrolysis (PubMed:18590734).
Not inhibited by cAMP (PubMed:18590734). Inhibited by zaprinast (PubMed:16038615, PubMed:18590734).
Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.
Belongs to the Tim17/Tim22/Tim23 family.
Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps.
Belongs to the peroxiredoxin family. Prx6 subfamily.
Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl-tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner.
Belongs to the eukaryotic ribosomal protein eS8 family. Ribosome biogenesis protein NSA2 subfamily.
Component of the pre-66S ribosomal particle.
Involved in the biogenesis of the 60S ribosomal subunit. May play a part in the quality control of pre-60S particles.
Belongs to the class I fructose-bisphosphate aldolase family.
Expressed during parasite asexual blood stages, including in schizonts (at protein level).
Homotetramer (PubMed:26289816). Interacts with TRAP (via cytoplasmic domain); the interaction prevents substrate binding and thereby inhibits aldolase activity (PubMed:26289816, PubMed:16321976) (Probable). Interacts with MTRAP (via cytoplasmic domain); MTRAP phosphorylation may increase the binding to FBPA (PubMed:16321976). Interact with RH1 (via cytoplasmic domain) (PubMed:22991428, PubMed:27607074). Interacts with RH2b (via cytoplasmic domain) (PubMed:22991428, PubMed:27607074). Interacts with RH4 (via cytoplasmic domain) (PubMed:22991428, PubMed:27607074). Interacts with AMA1 (via cytoplasmic domain); the interaction is weak, however it may be increased upon AMA1 phosphorylation (PubMed:27607074). Interacts with EBA140 (via cytoplasmic domain); the interaction is weak (PubMed:27607074). Interacts with EBA175 (via cytoplasmic domain); the interaction is weak (PubMed:27607074). Interacts with EBA181 (via cytoplasmic domain); the interaction is weak (PubMed:27607074). Interacts with G-actin and F-actin (PubMed:25261592). May interact with ACT2/actin II; the interaction inhibits FBPA catalytic activity (By similarity). Interacts with human SLC4A1/band 3 (via N-terminus); the interaction inhibits FBPA catalytic activity (By similarity).
Plays a key role in glycolysis by catalyzing the cleavage of fructose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (PubMed:26289816). Independently of its catalytic activity, connects the actin filaments, and thus the actomyosin motor, to cell surface adhesins of the thrombospondin-related anonymous protein (TRAP), the erythrocyte binding ligand (EBL) and reticulocyte binding homolog (RH) protein families; this interaction is probably involved in transducing the motor force across the parasite surface required for sporozoite and ookinete gliding motility and merozoite invasion (PubMed:22991428, PubMed:25261592) (Probable). Stimulates actin polymerisation (PubMed:25261592).
The cytoplasmic tail of TRAP and probably other adhesins acts as a competitive inhibitor as the binding sites of the glycolytic substrate fructose 1,6-bisphosphate and TRAP partially overlap.
Belongs to the universal ribosomal protein uL23 family.
Belongs to the dynactin subunits 5/6 family. Dynactin subunit 5 subfamily.
Belongs to the eukaryotic ribosomal protein eL31 family.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis.
Belongs to the Nudix hydrolase family. CPSF5 subfamily.
Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs. CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs.
Homodimer (via N- and C-terminus); binds RNA as homodimer. Component of the cleavage factor Im (CFIm) complex.
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP (PubMed:18973776). Has very low activity with CTP, GTP, ITP and UTP and no activity with GMP, UMP or IMP in vitro (PubMed:18973776).
May be palmitoylated at Cys-4 which stabilizes cell membrane localization of the myristoylated protein.
Monomer (PubMed:18973776). Oligomer (PubMed:18973776). Heterodimer composed of NMT and AK2; AK2 myristoylation stabilizes the complex (PubMed:18973776).
Myristoylation is required for cell membrane localization.
Belongs to the DEAD box helicase family. DDX18/HAS1 subfamily.
Belongs to the universal ribosomal protein uS12 family.
Belongs to the cAMP-dependent kinase regulatory chain family.
Belongs to the transketolase family. DXPS subfamily.
Belongs to the transferase hexapeptide repeat family.
Belongs to the SMC family. SMC2 subfamily.
May play a role in the conversion of interphase chromatin into condensed chromosomes.
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with smc4 forming a V-shaped heterodimer.
Belongs to the DPH1/DPH2 family. DPH1 subfamily.
Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2.
Belongs to the ERCC1/RAD10/SWI10 family.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly.
Part of the nascent polypeptide-associated complex (NAC).
Belongs to the eukaryotic release factor 1 family.
Heterodimer of two subunits, one of which binds GTP.
Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides (PubMed:17895246, PubMed:19574214, PubMed:27462122). In the food vacuole, involved in the final step of host hemoglobin catabolism, by cleaving hemoglobin-derived oligopeptides (PubMed:17895246, PubMed:19574214). In the cytoplasm, may be involved in the last steps of the turnover of ubiquitinated proteins (Probable).
Partially activated by Co(2+) and Mg(2+) has no effect (PubMed:19574214). Inhibited by 1 mM Zn(2+), Ni(2+), or Cu(2+) (PubMed:19574214). Inhibited by apstatin, a non-hydrolysable peptide analog (PubMed:27462122).
The N-terminus may be proteolytically cleaved to generate a 73-kDa mature form.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. IF-2 subfamily.
In the N-terminal section; belongs to the dsDNA virus mRNA guanylyltransferase family.
Belongs to the universal ribosomal protein uL29 family.
Belongs to the succinate/malate CoA ligase alpha subunit family.
Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and nucleotide specificity is provided by the beta subunit.
Belongs to the class I-like SAM-binding methyltransferase superfamily.
Belongs to the methyltransferase superfamily. METL family.
S-adenosyl-L-methionine-dependent methyltransferase.
Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.
Belongs to the IspD/TarI cytidylyltransferase family. IspD subfamily.
Belongs to the universal ribosomal protein uL30 family.
Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.
Diversity in S-antigen is mainly due to polymorphism in the repetitive regions.
S antigens are soluble heat-stable proteins present in the sera of some infected individuals.
Belongs to the archaeal Rpo5/eukaryotic RPB5 RNA polymerase subunit family.
Belongs to the adenylate kinase family. AK6 subfamily.
Broad-specificity nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Has also ATPase activity.
Belongs to the adaptor complexes medium subunit family. Delta-COP subfamily.
Plays a role in U6 snRNP assembly and function. Binds to the 3' end of U6 snRNA.
Belongs to the F-actin-capping protein beta subunit family.
F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments.
Belongs to the FPP/GGPP synthase family.
Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Involved in nucleotide excision repair.
Carrier of the growing fatty acid chain in fatty acid biosynthesis.
Belongs to the radical SAM superfamily. Lipoyl synthase family.
Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives.
Expressed maximally in the early stages and late stages of the parasite erythrocytic development.
Component of the PfRH5 adhesion complex composed of 1 copy of CyRPA, RH5 and RIPR; the complex is formed during merozoite invasion of host erythrocytes specifically at the interface between the parasite and host membranes (PubMed:21909261, PubMed:25583518, PubMed:27374406, PubMed:28186186, PubMed:30542156). Within the complex, interacts with CyRPA (PubMed:28186186, PubMed:30542156). CyRPA recruitment of RIPR to RH5-P113-BSG leads to the formation of the PfRH5 adhesion complex which probably in turn releases RH5 from P113 while maintaining the interaction of the PfRH5 adhesion complex with BSG (PubMed:28186186).
Conditional knockdown causes loss of cell growth and severely impairs merozoite invasion of erythrocytes. Attachment to and deformation of erythrocyte membrane is normal, however the subsequent step, which triggers an increase in Ca(2+) from the attached merozoite into the erythrocyte, is impaired.
Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:21909261, PubMed:25583518, PubMed:27374406, PubMed:27692771). As part of the PfRH5 adhesion complex, facilitates the interaction of RH5 and human BSG required for the Ca(2+) release into the erythrocyte (PubMed:27374406).
Expressed in late throphozoide to schizonts and in merozoites (at protein level).
Proteolytically cleaved into two chains of 125kDa and 65kDa which remain associated. The cleavage occurs at the schizont stage prior to the release of merozoites.
Serine protease which may cleave PFN/profilin.
Exerts its effect at some terminal stage of cytochrome c oxidase synthesis, probably by being involved in the insertion of the copper B into subunit I.
Has a role in nuclear-cytoplasmic transport of proteins and mRNAs.
Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts. Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome. Acts as ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step.
eIF-5A seems to be the only eukaryotic protein to have a hypusine residue which is a post-translational modification of a lysine by the addition of a butylamino group.
Belongs to the deoxyhypusine synthase family.
Belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family.
Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery. Required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the cytosolic Fe-S scaffold complex. Electrons are transferred from NADPH via a FAD- and FMN-containing diflavin oxidoreductase. Together with the diflavin oxidoreductase, also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit.
The C-terminal domain binds 2 Fe-S clusters but is otherwise mostly in an intrinsically disordered conformation.
The N-terminal domain has structural similarity with S-adenosyl-L-methionine-dependent methyltransferases, but does not bind S-adenosyl-L-methionine. It is required for correct assembly of the 2 Fe-S clusters.
The twin Cx2C motifs are involved in the recognition by the mitochondrial MIA40-ERV1 disulfide relay system. The formation of 2 disulfide bonds in the Cx2C motifs through dithiol/disulfide exchange reactions effectively traps the protein in the mitochondrial intermembrane space.
Activated by calcium (PubMed:19307175, PubMed:19666141). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (PubMed:19307175). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-234, which leads to the kinase activation (PubMed:19307175). Intracellular calcium increase is triggered by xanthurenic acid (XA), a small mosquito molecule that induces the differentiation of specialized transmission stages, the gametocytes, into male and female gametes (Probable). Activated by a decrease in temperature (20 degrees Celsius) and an increase in pH (7.6) occurring when the parasite is ingested by in the mosquito (PubMed:19666141).
Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (PubMed:19307175, PubMed:19666141). Plays a central role in the host erythrocytes and hepatocytes infection cycles, sexual reproduction and mosquito transmission of the parasite. During the liver stage, involved in sporozoite motility and thus in sporozoite invasion of host hepatocytes, probably together with CDPK1 and CDPK5. Involved in merosome egress from host hepatocytes, probably together with CDPK5. During the asexual blood stage, involved in merozoite invasion of host erythrocytes and motility by stabilizing the inner membrane complex, a structure below the plasma membrane which acts as an anchor for the glidosome, an acto-myosin motor. Required for cell cycle progression in the male gametocyte. During male gametogenesis in the mosquito gut, required to initiate the first round of DNA replication, probably by facilitating the assembly of the pre-replicative MCM complex, to assemble the first mitotic spindle and, at the end of gametogenesis, to initiate axoneme motility, cytokinesis and subsequent exflagellation. For each of these steps, may phosphorylate SOC1, SOC2 and SOC3, respectively. Together with CDPK1, regulates ookinete gliding in the mosquito host midgut (By similarity).
Expressed in gametocytes (at protein level).
Induced by xanthurenic acid (XA) and human serum.
May be autophosphorylated on Thr-234 in vitro.
May interact with the pre-replication MCM complex prior male gametogenesis activation.
Myristoylated; myristoylation may target it to different subcellular compartments. During male gametogenesis, myristoylation is required to initiate DNA replication but not for mitotic spindle assembly or axoneme activation.
Replication in host erythrocytes is normal.
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (PubMed:19307175). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (PubMed:19307175).
Belongs to the 5'-3' exonuclease family. XRN2/RAT1 subfamily.
Belongs to the thiolase-like superfamily. Thiolase family.
Causes a severe growth defect in host erythrocytes (PubMed:30127496). Export of protein containing a PEXEL motif, including PIESP2, PTP3 and PTP2 is severely reduced at the ring and trophozoite stages (PubMed:30127496). Similarly, export of RESA is reduced at the schizont stage (PubMed:30127496).
Component of the signal peptidase complex (SPC) composed of a catalytic subunit SEC11/SPC21 and three accessory subunits SPC25, SPC3/SPC22, SPC1/SPC12 (PubMed:30127496). The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates (By similarity). This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids (By similarity). Within the complex, interacts with SEC11/SPC21 (PubMed:30127496). Component of a complex composed of SPC25 and PMV; the interaction is mediated via the transmembrane domains (PubMed:30127496). The complex interacts with the SEC61 channel-forming translocon complex and is involved in the recognition and import of PEXEL motif-containing proteins into the ER for subsequent export (PubMed:30127496).
Component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (PubMed:30127496). Enhances the enzymatic activity of SPC and facilitates the interactions between different components of the translocation site (By similarity). Also, regulatory component of the CSP25-plasmepsin PMV complex which cleaves the pentameric localization motif RxLxE/Q/D (termed Plasmodium export element (PEXEL)) located downstream of the N-terminal secretory signal sequence of several proteins (PubMed:30127496).
Heterodimer; heterodimerizes with PF41. May form an antiparallel heterodimer with PF41.
Gametocyte surface protein required for male/female gamete fusion. Also required for male gamete exflagellation and interaction with host erythrocytes.
Heterodimer; heterodimerizes with PF45/48.
May be processed into a 310 kDa form as the parasite emerges from the host erythrocytes.
Promising transmission-blocking vaccine candidate: targeting the protein would prevents transmission of the parasite decreasing the malaria burden (PubMed:32709983, PubMed:33741942). The LMIV230-01 transmission-blocking antibody against the 6-Cys domain 1 also binds to the heterologous P.falciparum Malian isolate 20-2217-0 which carries a 'Ser-605' polymorphism and to the heterologous St Lucia strain which carries 'Ser-605' and 'Asn-661' polymorphisms (PubMed:33741942).
Specifically expressed in gametocytes and gametes (at protein level).
Belongs to the bacterial ribosomal protein bS16 family.
Belongs to the ubiquitin conjugation factor E4 family.
Belongs to the universal ribosomal protein uL13 family.
Belongs to the type IB topoisomerase family.
Belongs to the ATP-dependent DNA ligase family.
Belongs to the plant tobamovirus multiplication TOM1 protein family.
Binds 1 divalent metal cation per subunit; can use either Mg(2+) or Mn(2+).
Pyrophosphatase that hydrolyzes non-canonical purine nucleotides such as inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) or xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.
Belongs to the apicomplexan parasites AMA1 family.
Involved in parasite invasion of erythrocytes.
Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.
Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.
Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Belongs to the phosphoenolpyruvate carboxykinase (ATP) family.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. FabI subfamily.
Associates with 90S and pre-40S pre-ribosomal particles.
Component of the 90S pre-ribosome involved in the maturation of rRNAs. Required for early cleavages of the pre-RNAs in the 40S ribosomal subunit maturation pathway.
Belongs to the adenylosuccinate synthetase family.
Parasitic protozoa lack the de novo purine biosynthesis pathway and rely exclusively on the salvage pathway for their purine nucleotide requirements.
Plays an important role in the salvage pathway for purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP (By similarity).
Belongs to the eukaryotic ribosomal protein eL34 family.
Belongs to the RING-type zinc finger family. LOG2 subfamily.
May be involved in calcium-dependent ubiquitination and subsequent proteasomal degradation of target proteins. Probably serves as a molecular bridge in ubiquitin E3 complexes. Participates in the ubiquitin-mediated degradation of beta-catenin (CTNNB1).
Belongs to the Mediator complex subunit 6 family.
Belongs to the RNA polymerase beta chain family.
In plastids the minimal PEP RNA polymerase catalytic core is composed of four subunits: alpha, beta, beta', and beta''. When a (nuclear-encoded) sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription.
Belongs to the glutathione peroxidase family.
tRNA nucleus export receptor which facilitates tRNA translocation across the nuclear pore complex.
Belongs to the SLC35F solute transporter family.
Basal guanylate activity of the recombinant guanylate cyclase domains 1 and 2 is not modulated by an increase in Ca(2+) levels or by the gametogenesis inducer xanthurenic acid.
Binds 2 magnesium ions per subunit (By similarity). Is also active with manganese (in vitro) (Probable).
Catalyzes the synthesis of the second messenger cGMP from GTP (PubMed:10747978, PubMed:11703675, PubMed:18452584). Regulates cGMP production in gametocytes; however, is dispensable for the initiation of gametogenesis (PubMed:18452584). Does not have adenylate cyclase activity (PubMed:10747978).
During the blood stage, specifically expressed in gametocytes.
The N-terminus contains a P-type ATPase-like domain which is required for guanylate cyclase activity.
Belongs to the eukaryotic ribosomal protein eL22 family.
Belongs to the ATPase alpha/beta chains family.
Produces ATP from ADP in the presence of a proton gradient across the membrane.
Belongs to the eukaryotic ribosomal protein eS1 family.
Belongs to the GTP-binding SRP family. SRP54 subfamily.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).
The M domain binds the 7SL RNA in presence of SRP19 and binds the signal sequence of presecretory proteins.
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER.
Belongs to the ribonucleoside diphosphate reductase small chain family.
ATP hydrolysis occurs at the interface between the nucleotide-binding domains of subunits A and B (By similarity). ATP hydrolysis triggers a conformational change in the subunits D and F, which induces a shift of subunit d (By similarity). The c-ring is subsequently rotated and results in a continuous proton translocation across the membrane (By similarity).
Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:10915784). During the trophozoite stage, involved in the acidification of the extracellular space next to the cell membrane (PubMed:10915784).
Expressed during the asexual blood stage, including in trophozoites (at protein level).
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d and subunit e (By similarity).
Alternates between an inactive GDP-bound form and an active GTP-bound form (By similarity). Activated by guanine nucleotide-exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) (By similarity).
Belongs to the small GTPase superfamily. Rab family.
Expressed during the asexual blood stage, including the trophozoite and schizont stages (at protein level).
Interacts with CK1 (PubMed:22188458). May interact with ARF1 (PubMed:33604307).
Lacks the C-terminal cysteine motifs subject to isoprenylation present in mammalian RAB5B homolog.
Myristoylation is required for cell membrane and food vacuole membrane localization.
Small GTPase which regulates vesicle trafficking between organelles (Probable). May be involved in the trafficking of the N-myristoylated AK2 from the endoplasmic reticulum to the parasitophorous vacuole membrane (PubMed:27316546).
Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Expressed during the asexual blood stage, including at the schizont stage and in free merozoites (at protein level).
May play a role in the merozoite attachment to the erythrocyte.
Potential candidate for the development of parasite blood stage vaccines (PubMed:19428875, PubMed:28189425). In vivo, induces antibodies capable of inhibiting parasite growth in the host (PubMed:19428875). In vitro, antibodies to MSP2 do not appear to inhibit invasion directly but may function to opsonize merozoites and promote antibody-dependent cellular inhibition mediated by host monocytes (PubMed:19428875, PubMed:24218484). The ability of merozoites to carry antibodies bound to MSP2 into the invaded host erythrocyte without apparent disruption of invasion or growth may represent an adaption of the parasite to render antibodies to the merozoite surface non-functional, thereby contributing to immune evasion (PubMed:24218484).
The N-terminal region appears to be involved in lipid binding.
The sequence varies across Plasmodium strains (PubMed:2181307). All variants share conserved N- and C-terminal regions; however, they belong to two allelic families, represented by 3D7 strain and FC27 strain sequences respectively, distinguished by tandem repeats and dimorphic flanking sequences within the central region of the protein (PubMed:2181307).
Cysteine protease which plays an essential role in merozoite egress from host erythrocytes. May cleave host SPTB/beta spectrin and ANK1/ankyrin-1 which disrupts host erythrocyte actin cytoskeleton and leads to host erythrocyte cell membrane rupture.
Expressed during parasite asexual blood stages, specifically at the schizont stage (at protein level).
Just prior to merozoite egress from host erythrocytes, proteolytically cleaved by SUB1 to generate the active 75kDa form.
Activated by threonine and tyrosine phosphorylation.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily.
Belongs to the copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.
Belongs to the phosphofructokinase type A (PFKA) family. PPi-dependent PFK group II subfamily. Clade 'Long' sub-subfamily.
Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
Tetramer of two alpha (regulatory) and two beta (catalytic) chains.
Belongs to the sirtuin family. Class IV subfamily.
Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis. Cooperates with Sir2A to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance.
Belongs to the DDOST 48 kDa subunit family.
Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER).
Belongs to the spermidine/spermine synthase family.
In the C-terminal section; belongs to the DHPS family.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.
A Gly-cisPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of L-amino acids (PubMed:24302572, PubMed:27224426).
D-aminoacyl-tRNA deacylase, with no observable activity on tRNAs charged with their cognate L-amino acid (PubMed:20007323, PubMed:24302572, PubMed:27224426). Probably acts by rejecting L-amino acids from its binding site rather than specific recognition of D-amino acids (PubMed:27224426). Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr) (PubMed:20007323, PubMed:24302572, PubMed:27224426). Hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) (PubMed:27224426). Deacylates mischarged D.melanogaster and E.coli glycyl-tRNA(Ala) (PubMed:28362257). Probably acts via tRNA-based rather than protein-based catalysis (PubMed:24302572, PubMed:27224426). Acts on tRNAs only when the D-amino acid is either attached to the ribose 3'-OH or transferred to the 3'-OH from the 2'-OH through rapid transesterification (PubMed:24302572). Binds a number of other D-amino acids (D-Arg, D-Glu, D-His, D-Lys, D-Ser), suggesting it may also deacylate other mischarged tRNAs (PubMed:20007323).
In the crystal structures with bound ADP (PDB 3KO4, 3KO5), the adenosine moiety is thought to represent the authentic C-terminal adenosine of charged tRNA and is annotated as such in this entry (PubMed:20007323).
Initially the conserved reside Thr-90 was thought to be a nucleophile; mutagenesis in this organism and E.coli indicates it is not.
Expressed during the asexual blood stage.
Belongs to the PPP phosphatase family. PP-2B subfamily.
Belongs to the sirtuin family. Class III subfamily.
Expressed during the asexual blood stage, specifically during the trophozoite and schizont stages (at protein level) (PubMed:18397290, PubMed:22379140, PubMed:22006844, PubMed:36947546). Low or undetectable levels at the ring stage (PubMed:18397290, PubMed:22006844, PubMed:36947546).
Homotrimer. Dissociates into monomers on binding NAD. Interacts with ALBA3 (acetylated and unacetylated) (PubMed:22006844, PubMed:36947546).
Inhibited by nicotinamide. Inhibited by surfactin, which is a competitive inhibitor of NAD and an uncompetitive inhibitor of acetylated peptide.
Loss of binding to telomers and subtelomeric repeat regions (TAREs) and promoters of var genes.
NAD-dependent protein deacylase (PubMed:21992006). Catalyzes the NAD-dependent hydrolysis of medium and long chain fatty acyl groups from lysine residues (PubMed:21992006). Has weak NAD-dependent protein deacetylase activity (PubMed:17827348, PubMed:18729382, PubMed:18397290, PubMed:18221799, PubMed:20601220, PubMed:21992006). Regulates the endonuclease activity of ALBA3 by deacetylation of 'Lys-23' (PubMed:22006844, PubMed:36947546). Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis (PubMed:15820676, PubMed:22379140). Cooperates with Sir2B to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance (PubMed:19402747). Involved in recruiting ORC1 to the telomers and subtelomeric repeat regions (TAREs) and promoters of var genes (PubMed:22379140). Can ADP-ribosylate both histones and itself (PubMed:17827348). May also have a role in telomeric end protection (PubMed:18525026).
The reported ADP-ribosyltransferase activity of sirtuins is likely to be some inefficient side reaction of the deacetylase activity and may not be physiologically relevant.
Component of the coenzyme Q biosynthetic pathway. May play a role in organizing a multi-subunit COQ enzyme complex required for coenzyme Q biosynthesis. Required for steady-state levels of other COQ polypeptides.
Belongs to the class-II aminoacyl-tRNA synthetase family. Phe-tRNA synthetase alpha subunit type 2 subfamily.
Belongs to the eIF-2B gamma/epsilon subunits family.
Acts as a sulfur carrier required for 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Serves as sulfur donor in tRNA 2-thiolation reaction by being thiocarboxylated (-COSH) at its C-terminus by the MOCS3/UBA4 homolog. The sulfur is then transferred to tRNA to form 2-thiolation of mcm(5)S(2)U. Also acts as a ubiquitin-like protein (UBL) that is covalently conjugated via an isopeptide bond to lysine residues of target proteins. The thiocarboxylated form serves as substrate for conjugation and oxidative stress specifically induces the formation of UBL-protein conjugates.
C-terminal thiocarboxylation occurs in 2 steps, it is first acyl-adenylated (-COAMP) via the hesA/moeB/thiF part of the MOCS3/UBA4 homolog, then thiocarboxylated (-COSH) via the rhodanese domain of the MOCS3/UBA4 homolog.
Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seems to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack independent of vesicle origin.
Belongs to the queuine tRNA-ribosyltransferase family.
Catalyzes the hydrolysis of L-arginine into urea and L-ornithine, which is a precursor for polyamine biosynthesis (PubMed:15843155, PubMed:19456858, PubMed:20527960, PubMed:21728378). May play a role in parasite intra-hepatic development during the host liver stage (By similarity).
Expressed during the asexual blood stage; expression is high in rings and young trophozoites, and low in mature trophozoites and schizonts.
Feedback inhibition by product L-ornithine, (PubMed:15843155). Inhibited by 2(S)-amino-6-boronohexanoic acid (ABH); however, with less efficiency than human ARG1 (PubMed:20527960, PubMed:21728378).
Homotrimer; oligomerization is dependent on Mn(2+) binding.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.
Belongs to the DNA polymerase alpha subunit B family.
Belongs to the mitochondrion-specific ribosomal protein mS29 family.
Belongs to the XPG/RAD2 endonuclease family.
Belongs to the eukaryotic RPB8 RNA polymerase subunit family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively.
Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome, suggesting that it is involved in the minus-end nucleation of microtubule assembly.
Involved in calcium binding and microtubule stabilization.
Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state.
Involved in nucleotide metabolism via production of dUMP, the immediate precursor of thymidine nucleotides, and decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
Belongs to the pseudouridine synthase RsuA family.
Belongs to the SEC23/SEC24 family. SEC23 subfamily.
Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules.
Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.
Component of the PfRH5 adhesion complex composed of 1 copy of CyRPA, RH5 and RIPR; the complex is formed during merozoite invasion of host erythrocytes specifically at the interface between the parasite and host membranes (PubMed:25583518, PubMed:27374406, PubMed:30542156). Following the establishment of the junction between the merozoite and the erythrocyte, CyRPA dissociates from the complex (PubMed:30542156). Within the complex, interacts with RH5 and RIPR (PubMed:28195530, PubMed:30542156). CyRPA recruits RIPR to RH5-P113-BSG complex; the formation of the PfRH5 adhesion complex increases the affinity of RH5 for BSG and probably leads to the release of RH5 from P113 while maintaining the interaction of the PfRH5 adhesion complex with BSG (PubMed:28186186, PubMed:30542156).
CyRPA shares structural homology with sialidases, however the 3 conserved arginine residues involved in substrate binding and the nucleophilic tyrosine residue are not conserved. Does not have sialidase/neuraminidase activity in vitro.
CyRPA was thought to be GPI-anchored to the merozoite membrane (PubMed:25583518). However, a subsequent report shows that this was not the case (PubMed:27374406).
Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:22593616, PubMed:25583518, PubMed:27374406, PubMed:28195530, PubMed:28195038). Required for the assembly of the PfRH5 adhesion complex (or invasion complex) composed of CyRPA, RH5 and RIPR at the interface between the merozoite and the host erythrocyte membranes (PubMed:25583518, PubMed:28186186, PubMed:28195530, PubMed:28195038, PubMed:30542156). This facilitates the binding of RH5 to host receptor BSG/basigin, which leads to the establishment of a tight junction between the merozoite and host erythrocyte membranes and allows Ca(2+) release into the erythrocyte (PubMed:27374406, PubMed:28186186, PubMed:30542156).
Expressed during parasite asexual blood stages, specifically at the schizont stage, in free merozoites, and at the very early ring stage but not in late ring and early trophozoite stages (at protein level).
Conditional knockout at the ring stage has no effect on parasite development during the first cycle and merozoites egress normally from host erythrocytes. However, these merozoites are unable to reinvade new erythrocytes (PubMed:31492901, PubMed:32179747). Impaired rhoptry secretion during merozoite invasion of host erythrocytes (PubMed:31492901, PubMed:32179747). Increases the spatial segregation between rhoptry neck protein RON4 and bulb protein RAP1, and impairs RAP1 processing (PubMed:32179747). No effect on rhoptry morphology (PubMed:31492901, PubMed:32179747). Microneme secretion is not affected (PubMed:31492901).
During parasite asexual blood stages, expressed at the late schizont stage and in free merozoites (at protein level).
Essential for merozoite invasion of host cells by controlling rhoptry secretion (PubMed:31492901, PubMed:32179747). Binds to phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) lipids and thus, likely contributes to the assembly of the machinery that docks or primes the rhoptry to the parasite cell membrane prior to the fusion with the host cell membrane (PubMed:31492901).
The C2 domain is a non-calcium binding domain (By similarity). Cooperates with the PH domain in the binding to phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) (By similarity).
The PH domain cooperates with the C2 domain in the binding to phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2).
Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:11013257, PubMed:20673832). By modifying the redox status of targeted proteins, induces changes in their structure and activity (PubMed:19360125, PubMed:20673832). Reduces oxidized glutathione (GSSG), thereby acting as a backup for the glutathione redox system (PubMed:11013257). Reduces nitroglutathione (GSNO), a compound involved in the transport of nitric oxide (NO) (PubMed:11013257). Also reduces oxidative stress by detoxifying hydrogen peroxide, tert-butyl hydroperoxide and cumene hydroperoxide (PubMed:14962358). Activates ornithine aminotransferase OAT by reducing a disulfide bond in the substrate binding loop, thereby enhancing the affinity of OAT for its substrates (PubMed:20673832). May reduce S-adenosyl-L-homocysteine hydrolase SAHH (PubMed:19360125).
The disulfide bond between Cys-30 and Cys-33 acts as a redox-active center and is reduced by thioredoxin reductase TRXR.
Belongs to the steroid 5-alpha reductase family.
Bifunctional enzyme which catalyzes the first two steps of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis.
G6PD activity is inhibited by glucosamine-6-phosphate, NADPH, and 4-(4-bromophenyl)-7-(3,4-dimethoxyphenyl)-4,6,7,8-tetrahydroquinoline-2,5(1 H,3H)-dione. G6PD and 6PGL activities can be reversibly inhibited by S-glutathionylation (in vitro).
In the C-terminal section; belongs to the glucose-6-phosphate dehydrogenase family.
In the N-terminal section; belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.
Belongs to the plasmodium circumsporozoite protein family.
CSP immunodominant B cell epitopes are primarily located in the central repeats (PubMed:29554084). Antibodies against CSP and particularly against the central repeats can neutralize infection at the pre-liver stage and thus makes CSP an attractive candidate for the development of vaccines (PubMed:29554084, PubMed:32150583).
During host cell invasion, proteolytically cleaved at the cell membrane in the region I by a papain-like cysteine protease of parasite origin (By similarity). Cleavage is triggered by the sporozoite contact with highly sulfated heparan sulfate proteoglycans (HSPGs) present on the host hepatocyte cell surface (By similarity). Cleavage exposes the TSP type-1 (TSR) domain and is required for productive invasion of host hepatocytes but not for adhesion to the host cell membrane (By similarity). Cleavage is dispensable for sporozoite development in the oocyst, motility and for traversal of host and vector cells (By similarity).
Essential sporozoite protein (PubMed:29554084, PubMed:32150583). In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands (By similarity). In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes (PubMed:29554084, PubMed:32150583). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By similarity).
In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.
The GPI-anchor is essential for cell membrane localization and for sporozoite formation inside the oocyst.
The N-terminus is involved in the initial binding to heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (PubMed:27560376). The N-terminus masks the TSP type-1 (TSR) domain which maintains the sporozoites in a migratory state, enabling them to complete their journey to the salivary gland in the mosquito vector and then to the host liver. The unmasking of the TSP type-1 (TSR) domain when the sporozoite interacts with the host hepatocyte also protects sporozoites from host antibodies (By similarity).
The TSP type-1 (TSR) domain is required for sporozoite development and invasion. CSP has two conformational states, an adhesive conformation in which the TSP type-1 (TSR) domain is exposed and a nonadhesive conformation in which the TSR is masked by the N-terminus. TSR-exposed conformation occurs during sporozoite development in the oocyst in the mosquito vector and during host hepatocyte invasion. TSR-masked conformation occurs during sporozoite migration through the hemolymph to salivary glands in the mosquito vector and in the host dermis.
The sequence of the repeats varies across Plasmodium species and strains.
LSm subunits form a heteromer with a donut shape.
Probably involved with other LSm subunits in the general process of degradation of mRNAs.
Expressed during the asexual blood stage; expression is low at the ring stage, increases in trophozoites and early schizonts and sharply decreases in late schizonts (at protein level) (PubMed:12413950, PubMed:12464414, PubMed:26251451). Expressed during the sexual blood stage (PubMed:12464414).
Homotrimer (PubMed:12413950, PubMed:12464414, PubMed:26251451). Oligomer (PubMed:12413950). Interacts with ORC1 (via PIP-box motif) (PubMed:26251451). Interacts with FEN1 (PubMed:26251451).
Induced by DNA damage (at protein level).
May be involved in DNA damage response (PubMed:26251451). Appears not to be involved in DNA replication in trophozoites (PubMed:26251451).
5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair.
Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily.
Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.
The disulfide bond between Cys-154 and Cys-163 is reduced by TRX1 which increases OAT catalytic activity.
The enzyme has a very narrow substrate specificity and can only catalyze the transamination of alpha-ketoglutarate with ornithine or N-acetylornithine and, to a lesser extent, of glutamate-5-semialdehyde with glutamate and alanine.
Unlike for mammalian OATs, activity is increased by TRX1-mediated reduction of the disulfide bond between Cys-154 and Cys-163 (PubMed:20673832). Binding to TRX1 may also induce conformational changes that facilitate substrate binding (PubMed:20673832).
Belongs to the bacterial ribosomal protein bL33 family.
Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs.
Belongs to the eukaryotic ribosomal protein eL37 family.
Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner.
Involved in merozoite invasion of host erythrocytes.
The PEXEL motif is involved in the protein translocation through the parasitophorous vacuole membrane and into the host erythrocyte cytoplasm.
Belongs to the eukaryotic ribosomal protein eL39 family.
Aminopeptidase which preferentially cleaves leucine residues from the N-terminus of peptides (PubMed:17107951, PubMed:22359643, PubMed:34133730, PubMed:33536500, PubMed:21844374). Also, has some activity towards tryptophan and methionine and to a lesser extent towards phenylalanine (PubMed:17107951, PubMed:22359643, PubMed:34133730). Has very low activity or no activity towards the other amino acids (PubMed:17107951, PubMed:22359643, PubMed:34133730). In addition, cleaves the Cys-Gly dipeptide, probably as part of the glutathione regulation pathway; cleavage only occurs in the presence of Mn(2+) (PubMed:33303633). During the asexual blood stage, plays a role in the final step of host hemoglobin catabolism, by cleaving hemoglobin-derived oligopeptides providing a source of amino acids for the parasite protein synthesis and for the maintenance of osmotic homeostasis (PubMed:34133730). During the asexual blood stage, may also play a role during the ring-trophozoite transition (PubMed:21844374).
Binds 2 Zn(2+) ions per subunit (PubMed:19408962, PubMed:20133789, PubMed:21844374, PubMed:23713488, PubMed:25299353, PubMed:25645579, PubMed:35691342). Two metal binding sites with different affinities are located in the enzyme active site and can be occupied in vitro by different metals (PubMed:19408962). Site 1 binds metal with low affinity and can be occupied by Zn(2+), Mn(2+), Co(2+) or Mg(2+) (PubMed:19408962). While Zn(2+) has the highest affinity for site 1, catalytic activity is the highest with Mn(2+) or Co(2+) and less with Mg(2+) (PubMed:19408962, PubMed:33303633). Site 2 binds tightly to the metal ion and can be occupied only by Zn(2+) or Co(2+) (PubMed:19408962). A third metal binding site is also present in an inactive conformation of the hexamer; in this conformation only the metal binding sites 1 and 3 are occupied (PubMed:35691342).
Expressed during the asexual blood stage, including in rings, trophozoites and schizonts (at protein level).
Homohexamer composed of dimer of trimers (PubMed:17107951, PubMed:33303633, PubMed:35691342). Both the identity and concentration of metal ions available dictate the extent to which oligomerization occurs; Mn(2+) and Co(2+) induces oligomerization, whereas Mg(2+) has no effect, and Zn(2+) causes irreversible protein aggregation in vitro (PubMed:33303633).
Oligomerization is required for catalytic activity and is metal-dependent (PubMed:33303633, PubMed:35691342). The type of metal that binds the 2 metal binding sites influences catalytic activity and substrate specificity (PubMed:17107951, PubMed:19408962, PubMed:33303633). In vitro, activated by Co(2+), Mn(2+), Ni(2+), Mg(2+) and Zn(2+) with decreasing strength (PubMed:17107951, PubMed:19408962, PubMed:33303633). Occupancy of the site 2 is essential and sufficient for activating the enzyme but occupation of the 2 sites is necessary for full catalytic activity (PubMed:19408962). Inhibited by fungal metabolite bestatin (PubMed:17107951, PubMed:19408962, PubMed:34133730). Inhibited by Phe-Naphthyl (PNAP) (PubMed:21844374).
The L13 loop movement regulates the transition between active and inactive conformations by repositioning Lys-386, which, in turn, mediates the rearrangement of the binuclear metal center.
By binding to host chemokine CX3CL1, mediates the cytoadherence of host erythrocytes infected with parasite mature forms (late trophozoite and schizont) to endothelial cells, which sequesters them away from the circulation and thus prevents their elimination by the host spleen.
Expressed during the asexual blood stage in late rings, trophozoites and schizonts (at protein level) (PubMed:27653778, PubMed:32184257). Expressed in gametocytes from stages I to IV (at protein level) (PubMed:27653778, PubMed:20332084).
Monomer (PubMed:27653778). May form homodimers or homotrimers (PubMed:27653778). Interacts with MAHRP1 (PubMed:32184257). Interacts (via extracellular domain) with human chemokine CX3CL1; the interaction mediates the adhesion of infected erythrocytes with endothelial cells (PubMed:27653778).
Potential vaccine candidate as CBP1-based peptides or antibodies against CBP1 prevents adhesion of infected erythrocytes to endothelial cells.
The P.falciparum Export Element (PEXEL) motif, also known as the vacuolar transport signal (VTS), is a pentameric sequence (RxLxE/Q/D) required for the translocation of proteins across the parasitophorous vacuole membrane (Probable). In the endoplasmic reticulum, the motif is cleaved after the leucine residue and the N-terminus is N-acetylated (PubMed:20332084).
Belongs to the universal ribosomal protein uL2 family.
Belongs to the eukaryotic ribosomal protein eL27 family.
Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family.
Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Belongs to the CTL (choline transporter-like) family.
Belongs to the DNA mismatch repair MutS family.
Component of the post-replicative DNA mismatch repair system (MMR).
Belongs to the clathrin heavy chain family.
Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments.
V-ATPase is a heteromultimeric enzyme composed of a peripheral catalytic V1 complex attached to an integral membrane V0 proton pore complex.
Belongs to the proteasome subunit S11 family.
Associates with the 60S ribosomal subunit of the 80S translational complex.
Cotranslationally removes the N-terminal methionine from nascent proteins (PubMed:16983082, PubMed:27023914). The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val) (By similarity). May play an important role in parasite growth during the blood asexual stage (PubMed:16983082).
Highest activity with zinc and cobalt ions, and low activity with manganese or divalent iron ions (PubMed:27023914). Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with zinc, cobalt, manganese or divalent iron ions. Has high activity with zinc; zinc cofactor is transferred into the active site region by the ZNG1 zinc chaperone (By similarity).
Inhibited by pyrimidine derivative XC11.
Gametocyte surface protein required for male fertility.
Heterodimer; heterodimerizes with PF230.
Promising transmission-blocking vaccine candidate: targeting the protein would prevent transmission of the parasite decreasing the malaria burden. However, efforts to produce full length recombinant protein in a functional conformation is difficult. Different approaches have been tested to produce a recombinant protein with display of its transmission-blocking epitopes.
Belongs to the eukaryotic ribosomal protein eS28 family.
Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.
Belongs to the archaeal Rpo6/eukaryotic RPB6 RNA polymerase subunit family.
Activation may be calcium-dependent (PubMed:16879884). Inhibited by the non-covalent interaction with the cleaved propeptide (PubMed:16879884, PubMed:19214190).
Proteolytically cleaved at the N-terminus to generate a 74kDa intermediate which is further processed into a 72kDa form (PubMed:23834729). The first maturation cleavage is autocatalytic, occurs in the ER and is necessary for the subsequent SUB2 trafficking to the microneme (PubMed:23834729). The second cleavage may be mediated by PMX/plasmepsin X (PubMed:32109369).
Serine protease which plays an essential role in the shedding of AMA1, MSP1 and MSP7 from the surface of the invading merozoite; this step is essential for productive invasion and the release of the adhesion between the erythrocyte and the merozoite (PubMed:16879884, PubMed:19214190). May cleave TRAMP/PTTRAMP, thereby shedding TRAMP from the merozoite surface during erythrocyte invasion (PubMed:16879884).
The cytoplasmic domain is required for the correct redistribution at the merozoite surface and posterior capping but is dispensable for its progression through the secretory pathway.
The propeptide domain acts as an intramolecular chaperone for the folding of the catalytic domain (By similarity). Also acts as an inhibitor of the catalytic domain thereby regulating SUB2 activity during secretion (PubMed:16879884, PubMed:19214190).
The transmembrane domain is required for SUB2 progression through the secretory pathway.
Does not require processing for targeting to the food vacuole or maturation.
Expressed during the asexual blood stage; expression begins at the late ring, early trophozoite stage, increases in the mid-trophozoite stage, and persists throughout the schizont stage (at protein level).
In the food vacuole, acts downstream of proteases plasmepsins PMI and PMII and falcipains during the catabolism of host hemoglobin by cleaving peptide fragments of alpha and beta hemoglobin subunits generated by PMI and PMII and falcipains (PubMed:17074076). In the apicoplast, degrades apicoplast transit peptides after their cleavage (PubMed:17074076). Prefers bulky hydrophobic amino acids in the P1' position at both acidic and neutral pH (By similarity). At P2', prefers hydrophobic residues at acidic pH; at neutral pH, these same residues are abundant but prefers Arg (By similarity). At P3', prefers hydrophobic residues, especially Met, at both pH conditions. At P4' and P5', prefers acidic residues at acidic pH, however, at neutral pH, the enzyme is less selective at these positions (By similarity). The optimal site cleavage at acidic pH is YNEHS-|-FFMEE and, at neutral pH, MKRHS-|-FRMRG (By similarity).
Belongs to the GPI inositol-deacylase family.
Involved in inositol deacylation of GPI-anchored proteins which plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins.
Belongs to the V-ATPase E subunit family.
Ca(2+) does not appear to affect catalytic activity.
Expressed during the parasite blood stage, specifically in schizonts, and gametocytes (at protein level).
In contrast to other metacaspases of the peptidase C14B family, the catalytic histidine and cysteine residues do not appear to be conserved.
Protease that cleaves specifically after arginine or lysine residues (PubMed:29317266, PubMed:32202613). May play a role in parasite growth and/or development (PubMed:29317266, PubMed:32202613).
Component of the glideosome complex composed of GAP50, GAP45, MTIP and MyoA; the complex is formed during the late schizont stage and in merozoites (PubMed:16750579). MyoA, MTIP and GAP45 probably form an initial complex in the cytoplasm which is then recruited to the outer face of the inner membrane complex via the interaction with GAP50 (PubMed:16750579). Interacts with ACT1.
Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity).
This protein differs from the typical myosin heavy chain structure in having head and tail domains but no discernible neck domain.
Belongs to the type IA topoisomerase family.
Introduces a single-strand break via transesterification at a target site in duplex DNA. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand.
Auxiliary protein of DNA polymerase delta and is involved in the control of DNA replication by increasing the polymerase processibility during elongation of the leading strand (By similarity). Involved in DNA damage response (PubMed:26251451).
Homotrimer (PubMed:26251451, PubMed:30052905). Interacts with ORC1 (via PIP-box motif); the interaction occurs during DNA replication in trophozoites (PubMed:18554328, PubMed:26251451). Interacts with ORC5; the interaction occurs during the trophozoite stage but not at the late schizont stage (PubMed:18554328, PubMed:19633266, PubMed:26251451). Interacts with FEN1 (PubMed:26251451).
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM61 family.
Belongs to the eukaryotic-type primase small subunit family.
Catalytic subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex - primosome/replisome) which play an essential role in the initiation of DNA synthesis (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (By similarity).
Heterodimer of a catalytic subunit and a regulatory subunit, also known as the DNA primase complex.
The bound zinc ion is not a cofactor. It is bound to a zinc knuckle motif that may be involved in sequence recognition and the binding of ssDNA (By similarity).
The presence of the regulatory subunit accelerates the kinetics of initiation and primer extension.
Maintains high levels of reduced glutathione in the cytosol.
Produced by alternative initiation at Met-47 of isoform 2.
Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines.
Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a role in catalysis, but is probably involved in the proper positioning of the enzyme along the DNA strand.
Belongs to the small GTPase superfamily. SAR1 family.
Belongs to the glutamine synthetase family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM4 family.
S-adenosyl-L-methionine-dependent protein-lysine N-methyltransferase that methylates elongation factor 1-alpha.
Belongs to the VPS10-related sortilin family.
Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase TrmH family.
Belongs to the calcineurin regulatory subunit family.
During the asexual blood stage, binds to a sialic acid containing receptor on the surface of the host erythrocyte and thus is involved in merozoite invasion (PubMed:18617995). Binds erythrocytes via a neuraminidase sensitive and trypsin-, chymotrypsin-resistant receptor (PubMed:11733572, PubMed:18617995). After merozoite attachment and reorientation, RH1 binding to its erythrocyte receptor triggers an increase in intracellular Ca(2+) within the parasite resulting in the release of microneme proteins such as EBA175 which in turn leads to the formation of the tight junction between parasite and host cell (PubMed:24280897).
Expressed during parasite asexual blood stages, specifically at the late schizont stage prior to merozoite release and in free merozoites (at protein level) (PubMed:11733572, PubMed:12228308, PubMed:15612925). Expression levels are low in isolate 3D7 when compared to other isolates (at protein level) (PubMed:12228308, PubMed:15612925, PubMed:18617995).
May in part interact with AMA1 in the moving tight junction between the parasite and the erythrocyte membranes; the interaction may facilitate junction formation and active invasion.
No difference in the ability to invade neuraminidase-, trypsin or chymotrypsin-treated host erythrocytes compared with wild-type.
Possible candidate for an effective malaria vaccine as determined by epitope response in sera (PubMed:17653272). Antibodies against the erythrocyte binding domain (EBD) prevent merozoite invasion of host erythrocytes (PubMed:18617995, PubMed:24280897). However, inhibition efficiency varies across isolates due to the variation in RH1 expression levels and can also be affected by the expression levels of RH2a and/or RH2b, two other erythrocyte binding receptors (PubMed:18617995). Isolates 3D7 or HB3 are insensitive to antibodies against EBD while isolates W2mef, T994, FCR3 and Dd2 are sensitive (PubMed:18617995, PubMed:24280897).
Proteolytically processed into multiple fragments following schizont rupture (PubMed:19614665, PubMed:32452132). In the mature schizont stage prior to merozoite release, full length RH1 is processed post-Golgi into a 240 kDa N-terminal form and a 120 kDa C-terminal form containing the transmembrane region (PubMed:12228308, PubMed:15612925, PubMed:19614665, PubMed:32452132). Both forms appear not to form a complex (PubMed:19614665). However, they appear to remain in close proximity in late schizonts (PubMed:32452132). Following merozoite invasion of host erythrocytes, the 240 kDa form is further processed into a 140 kDa form which may be involved in the disengagement of the ligand-receptor complex required during the invasion process (PubMed:19614665, PubMed:32452132). Also, the 120 kDa is further cleaved into a 110 kDa form and a transmembrane 9 kDa form probably by ROM4 (PubMed:17040128, PubMed:19614665, PubMed:32452132).
RH1 expression levels greatly vary between isolates in part due to multiple RH1 gene copies; levels are high in isolates W2mef, FCR3, FCB1 and T994, and low in isolates 3D7, HB3, K1, 7G8, T996 and Dd2 (PubMed:12228308, PubMed:15612925, PubMed:18617995). A similar variation in expression affects other reticulocyte-binding proteins such as RH2a and RH2b (PubMed:12228308). The expression pattern of RH1 and RH2 allows the strain to use different invasion pathways to enter erythrocytes (Probable). This provides a mechanism of phenotypic variation to evade host immune responses and to adapt to the polymorphic nature of the erythrocyte receptors in human populations (Probable).
Belongs to the SMC family. SMC5 subfamily.
Apurinic/apyrimidinic (AP) endonuclease activity is enhanced with increasing concentrations of Mn(2+), while Zn(2+) initially enhances activity but subsequently inhibits activity in a concentration-dependent manner (PubMed:31386260). Co(2+) inhibits apurinic/apyrimidinic (AP) endonuclease activity at concentrations greater than 2.5 mM (PubMed:31386260).
Belongs to the AP endonuclease 2 family.
May be proteolytically cleaved into a 59 kDa form.
Plays a role in mitochondrial DNA base excision repair (BER) pathway induced by oxidative stress (PubMed:31386260). Has apurinic/apyrimidinic (AP) endonuclease activity towards double-stranded DNA (dsDNA) with a preference for C as opposite base (PubMed:31386260). Has 3'-phosphatase activity; removes 3'-phosphate from blunt-end, recessed, and gapped DNA templates and thus, removes 3'-blocks for DNA polymerase activity during BER (PubMed:31386260). Lacks 3'-5' exonuclease activity and does not cleave damaged bases by nucleotide incision repair (NIR) (PubMed:31386260).
Belongs to the DEAD box helicase family. eIF4A subfamily.
Belongs to the poly(A) polymerase family.
Binds 2 magnesium ions. Also active with manganese.
Polymerase that creates the 3'-poly(A) tail of mRNA's.
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Belongs to the proteasome subunit S1 family.
Belongs to the mitochondrion-specific ribosomal protein mL41 family.
Required for the retention of luminal endoplasmic reticulum proteins. Determines the specificity of the luminal ER protein retention system. Also required for normal vesicular traffic through the Golgi (By similarity).
Belongs to the V-ATPase D subunit family.
Belongs to the metallo-dependent hydrolases superfamily. DHOase family. Class II DHOase subfamily.
Belongs to the TRAFAC class YlqF/YawG GTPase family. NOG2 subfamily.
GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation.
Belongs to the glycosyltransferase 28 family.
Belongs to the phage and mitochondrial RNA polymerase family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TrmB family.
Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA.
Belongs to the F-actin-capping protein alpha subunit family.
Belongs to the eukaryotic ribosomal protein eS30 family.
Belongs to the myo-inositol 1-phosphate synthase family.
Key enzyme in myo-inositol biosynthesis pathway that catalyzes the conversion of glucose 6-phosphate to 1-myo-inositol 1-phosphate in a NAD-dependent manner (By similarity). Rate-limiting enzyme in the synthesis of all inositol-containing compounds (By similarity). De novo-synthesized myo-inositol is essential for incorporation into GPI (glycosylphosphatidylinositol) glycolipids during intra-erythrocytic development (PubMed:24350823).
During the asexual blood stage, initiates the proteolytic maturation of several rhoptry proteins and thus, is required for merozoite invasion of host erythrocytes and probably the subsequent development of the ring-stage (PubMed:29074775, PubMed:32109369). Cleaves rhoptry associated protein 1 RAP1 and apical sushi protein ASP during schizont maturation (PubMed:29074775, PubMed:32109369). Also cleaves rhoptry protein RON3 (PubMed:32109369).
Expressed during the asexual blood stage, in schizonts and free merozoites (at protein level).
Inhibited by small molecule 49c (PubMed:29074775). Inhibited by small molecule WM382 (PubMed:32109369).
It is unclear if PMIX is glycosylated as other members of the same enzyme family, i.e. PMI and PMII, are not.
Normal asexual development in host erythrocytes (PubMed:29074775). Egress from erythrocytes is normal; however, subsequent erythrocyte invasion by newly released merozoites is severely impaired (PubMed:29074775). Accumulation of RAP1 p86 precursor resulting from impaired processing (PubMed:29074775). Impaired ASP processing (PubMed:29074775). Impaired secretion of CyRPA during merozoite egress from erythrocytes (PubMed:29074775).
Forms a complex composed of RH5, P113 and human BSG/basigin; the complex bridges the merozoite and host erythrocyte membranes (PubMed:28186186). Within the complex, interacts with RH5 (via N-terminus); the interaction tethers RH5 to the merozoite membrane (PubMed:28186186).
Membrane receptor which tethers secreted RH5 to the merozoite membrane during merozoite invasion of host erythocytes.
Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.
Plays an important role in regulating the size of autophagosomes during the formation process.
Belongs to the acetyltransferase family. ARD1 subfamily.
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. YchF/OLA1 subfamily.
Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP.
Belongs to the polyprenol kinase family.
Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage.
Belongs to the tRNA(His) guanylyltransferase family.
Belongs to the eukaryotic initiation factor 4E family.
Belongs to the cytochrome c oxidase subunit 2 family.
Belongs to the uroporphyrinogen-III synthase family.
Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III.
Belongs to the eukaryotic ribosomal protein eS24 family.