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CATALYTIC ACTIVITY ATP + a protein = ADP + a phosphoprotein.CATALYTIC ACTIVITY ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.TISSUE SPECIFICITY Ubiquitous.PTM Dephosphorylation of Thr-186 by PPM1A and PPM1B blocks CDK9 activity and may lead to CDK9 proteasomal degradation. However, PPP1CA-mediated Thr-186 dephosphorylation is required to release P-TEFb from its inactive P-TEFb/7SK snRNP complex. Dephosphorylation of C-terminus Thr and Ser residues by protein phosphatase-1 (PP1) triggers CDK9 activity, contributing to the activation of HIV-1 transcription.PTM Polyubiquitinated and thus activated by UBR5. This ubiquitination is promoted by TFIIS/TCEA1 and favors 'Ser-2' phosphorylation of RPB1/POLR2A CTD.DISEASE Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.MISCELLANEOUS CDK9 inhibition contributes to the anticancer activity of most CDK inhibitors under clinical investigation (PubMed:18423896 and PubMed:21779453). As a retroviruses target during the hijack of host transcription (e.g. HIV), CDK9 inhibitors might become specific antiretroviral agents (PubMed:18423896). May be a target for cardiac hypertrophy future treatments (PubMed:19757441 and PubMed:18423896). May also be a target in anti-inflammatory therapy in innate immunity and systemic inflammation (PubMed:18728388).SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.SIMILARITY Contains 1 protein kinase domain.
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SIMILARITY Belongs to the VPS37 family.SIMILARITY Contains 1 VPS37 C-terminal domain.
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SIMILARITY Belongs to the RRM NELF-E family.SIMILARITY Contains 1 RRM (RNA recognition motif) domain.
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Membrane binding and targetting of GAG proteins
One of the mysteries of Gag protein involvement in HIV virion assembly is how the proteins are targeted to the proper membrane for budding. Infectious retroviruses do not bud from all of the available membrane surfaces within an infected cell, but primarily from the plasma membrane, which constitutes a small proportion of the total membrane surface in most cells. In polarized cells, the sites of budding are further restricted to the basolateral membrane.
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N-myristoylation of GAG polyprotein by NMT2
The amino terminal glycine residue of HIV-1 Gag polyprotein is myristoylated (Henderson et al. 1992). Myristoylation of newly synthesized Gag occurs in the cytosol of the infected host cell, with myristoyl-CoA as the myristate donor and the host cell NMT2 enzyme as the catalyst. Human cells express two isoforms of N-myristoyl transferase (NMT) (Giang and Cravatt 1998). The argumant that the second isoform catalyzes this reaction is indirect, based on the the observations that a stable enzyme:substrate complex forms transiently during the reaction (Farazi et al. 2001), and that Gag polyprotein can be found complexed with NMT2 (but not NMT1) in HIV-1-infected human cells (Hill and Skowronski 2005).
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Gap repair completes provirus integration
The mechanism by which the integration reaction is completed has not been fully clarified. Unfolding of the integration intermediate resulting from the IN-catalyzed transesterification produces a branched DNA molecule. Denaturation of the host DNA between the points of joining produces DNA gaps at each host-virus DNA junction. How these gaps are repaired is unclear. Well studied host cell gap repair enzymes can carry out this repair step on model virus-host DNA junctions in vitro, providing candidate enzymes. However, efforts to show importance in vivo are complicated by the fact that the functions are either redundant or lethal when mutated. Because the strand transfer complex formed at the completion of integration is quite stable, there may be a requirement for a disassembly step to remove integrase and potentially other proteins to allow access of the gap repair machinery. In order to complete the last stages of integration, the viral proteins must be removed, and the gaps at the host virus DNA junctions repaired. The sequence in which the dissembly of PIC occus is not yet understood.
Edited: Gopinathrao, G, D'Eustachio, P, 2006-05-18 20:10:22
Authored: Gopinathrao, G, D'Eustachio, P, 2006-05-18 20:10:22
Gag is translated from the unspliced viral RNA on free ribosomes in the cytoplasm. The products of the pro and pol genes are also synthesized from the unspliced viral RNA, but never as parts of an independent polyprotein. They are initially contained within the Gag-Pro or Gag-Pro-Pol fusion protein, the product of translational readthrough
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Once transported to the plasma membrane the VPU protein will be incorporated into the assembling virus. The Vpu accessory protein is found to be required for efficient virion release from some cell lines but completely dispensible in others.
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Formation of the P-TEFb(Cyclin T1:Cdk9) complex
Tat associates with the Cyclin T1 subunit of the cellular kinase complex TAK/P-TEFb and recruits this complex to the TAR sequence in the HIV-1 RNA (Wei et al. 1998). This association between TAT, TAR and TAK/P-TEFb is believed to bring the catalytic subunit of TAK/P-TEFb in close proximity to Pol II where it hyperphosphorylates the CTD of Pol II .
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VPU is shuttled through the ER:Golgi protein expression pathway.
How the PIC finds favored sites on target DNA has not been fully clarified. Active genes are favored for integration, and favored sequences at the site of integration also influence the reaction. Studies of cells depeleted in PSIP1/LEDGF/p75 suggest that this protein acts as a tethering factor binding HIV PICs near integration target DNA. Access of PICs to sites on chromosomes may be significant, since centromeric alphoid repeats are disfavored for integration, perhaps due to wrapping in compact centromeric heterochromatin. Nucleosomes bound to the integration template also affect target site selection and integration complex binding.
Transesterification to connect viral DNA 3' ends to host DNA 5' ends
The first chemical step of integration involves a single step transesterification, in which the recessed 3' hydroxyl of the viral DNA becomes covalently joined to a protruding 5' end in the target DNA. This step at the same time cleaves the target DNA.
In order for Rev to function, multiple molecules must bind sequentiallly to the RRE (Malim and Cullen 1991).
Authored: Matthews, L, Rice, AP, 2005-07-27 00:00:00
Rev molecules assemble onto the RRE RNA sequence through their ARM sequence
Nuclear export of the unspliced and partially spliced HIV-1 transcripts requires the association of the HIV-1 Rev protein with a cis-acting RNA sequence known as the Rev Response Element (RRE) located within the env gene. The RRE forms a stem loop structure that associates with an arginine-rich RNA binding motif (ARM) within Rev.
MISCELLANEOUS Inhibitors targeting HIV-1 viral envelope proteins are used as antiretroviral drugs. Attachment of virions to the cell surface via non-specific interactions and CD4 binding can be blocked by inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs, PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-induced conformational changes. Env interactions with the coreceptor molecules can be targeted by CCR5 antagonists including SCH-D, maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4 antagonist AMD 070. Fusion of viral and cellular membranes can be inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249). Resistance to inhibitors associated with mutations in Env are observed. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
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SIMILARITY Belongs to the eukaryotic RPB4 RNA polymerase subunit family.
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Retroviral DNA integration: reaction pathway and critical intermediates
HIV cDNA integration: molecular biology and inhibitor development
The biology and enzymology of protein N-myristoylation
The ups and downs of gene expression and retroviral DNA integration
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FUNCTION Matrix protein p17 targets Gag and Gag-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex. Implicated in the release from host cell mediated by Vpu.FUNCTION Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex.FUNCTION Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers.PTM Capsid protein p24 is phosphorylated.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).SIMILARITY Belongs to the primate lentivirus group gag polyprotein family.SIMILARITY Contains 2 CCHC-type zinc fingers.
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Human N-myristoyltransferases form stable complexes with lentiviral nef and other viral and cellular substrate proteins
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CATALYTIC ACTIVITY Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.CATALYTIC ACTIVITY Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.CATALYTIC ACTIVITY 3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.CATALYTIC ACTIVITY Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).ENZYME REGULATION The viral protease is inhibited by many synthetic protease inhibitors (PIs), such as amprenavir, atazanavir, indinavir, loprinavir, nelfinavir, ritonavir and saquinavir. RT can be inhibited either by nucleoside RT inhibitors (NRTIs) or by non nucleoside RT inhibitors (NNRTIs). NRTIs act as chain terminators, whereas NNRTIs inhibit DNA polymerization by binding a small hydrophobic pocket near the RT active site and inducing an allosteric change in this region. Classical NRTIs are abacavir, adefovir (PMEA), didanosine (ddI), lamivudine (3TC), stavudine (d4T), tenofovir (PMPA), zalcitabine (ddC), and zidovudine (AZT). Classical NNRTIs are atevirdine (BHAP U-87201E), delavirdine, efavirenz (DMP-266), emivirine (I-EBU), and nevirapine (BI-RG-587). The tritherapies used as a basic effective treatment of AIDS associate two NRTIs and one NNRTI. Use of protease inhibitors in tritherapy regimens permit more ambitious therapeutic strategies.DOMAIN The tryptophan repeat motif is involved in RT p66/p51 dimerization.DOMAIN Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D(35)E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein.PTM Capsid protein p24 is phosphorylated.PTM Matrix protein p17 is tyrosine phosphorylated presumably in the virion by a host kinase. This modification targets the matrix protein to the nucleus.MISCELLANEOUS Capsid protein p24 is able to bind macaque TRIM5-alpha or owl monkey TRIMCyp, preventing reverse transcription of the viral genome and succesfull infection of macaque or owl monkey by HIV-1.MISCELLANEOUS The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).MISCELLANEOUS Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in this entry which is a representative of clade B.SIMILARITY Contains 2 CCHC-type zinc fingers.SIMILARITY Contains 1 integrase catalytic domain.SIMILARITY Contains 1 integrase-type DNA-binding domain.SIMILARITY Contains 1 integrase-type zinc finger.SIMILARITY Contains 1 peptidase A2 domain.SIMILARITY Contains 1 reverse transcriptase domain.SIMILARITY Contains 1 RNase H domain.
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SIMILARITY Belongs to the NELF-B family.
TAK, an HIV Tat-associated kinase, is a member of the cyclin-dependent family of protein kinases and is induced by activation of peripheral blood lymphocytes and differentiation of promonocytic cell lines
The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding
RNA Polymerase II holoenzyme complex (hyperphosphorylated):TFIIF complex
RNA Polymerase II holoenzyme complex (hyperphosphorylated)
Transport of trimeric gp41:gp120 to plasma membrane
The cleaved and assembled gp41:gp121 complexes are transport to teh plasma membrane. This complex ultimately arrives via the cellular secretion pathway. Env is an integral membrane protein shuttled through the ER and Golgi where it was glycosylated and cleaved into the gp41 and gp120 subunits. The trimeric complex is brought to the plasma membrane by the host vesicular transport system. Only 7-14 trimers are present per virion.
Tat-containing early elongation complex with hyperphosphorylated Pol II CTD and phospho-NELF
Folding and Oligomerization of ENV glycoprotein
The monomeric GP160 ENV precursor protein assembles into a trimer.
There are numerous N-linked glycosylation sites that are important for infectivity of human immunodeficiency virus type 1. With more than 20 consensus N-linked glycosylation sites in gp120 it is expected that a number are important for virion function.
Cleavage of the viral Env gp160 precursor polyprotein
The trimeric gp160 complexes are cleaved into the gp41 and gp120 subunits by the cellular protease furin.
Transport of trimeric ENV precursor to Golgi apparatus
The trimeric ENV precursor complex is transported from the ER to the Golgi.
Phosphorylation of DSIF by the P-TEFb(Cyclin T1:Cdk9) complex
Phosphorylation of the Spt5 subunit of DSIF by P-TEFb(Cyclin T1:Cdk9) results in the conversion of DSIF to an elongation factor (Ivanov al. 2000).
Translocation of Vpr to the mitochondria
The ENV precursor protein gp160 is synthesized.
Tat-containing early elongation complex with hyperphosphorylated Pol II CTD ( phospho-NELF phospho DSIF)
HIV is characterized by the production of multiple-spliced RNA species. The genomic fragmant is processesed creating multiple mRNA fragments.
HIV-1 integration in the human genome favors active genes and local hotspots
Integration of viral DNA into host genomic DNA
Following nuclear entry, the viral preintegration complex (PIC) must select a site for integration in a host cell chromosome, and then carry out the chemical steps of the reaction. At the chromosomal level, HIV has been found to favor active transcription units for integration. Subsequent studies established that the cellular PSIP1/LEDGF/p75 protein is important in this reaction. PSIP1/LEDGF/p75 binds tightly to HIV integrase, and also to chromatin. Knocking down PSIP1/LEDGF/p75 in cells resulted in several perturbations of integration targeting in vivo, including reduced integration in transcription units. Thus PSIP1/LEDGF/p75 has been hypothesized to act as a tethering factor that dictates at least in part the placement of HIV integration sites. The integration target DNA is also expected to be coated with nucleosomes. Tests of integration into mononucleosomes in vitro have shown that wrapping integration target DNA actually boosts integration activity. Kinked positions on the DNA gyre are particularly favored for integration. Integration does not take place at a unique sequence in the integration target DNA (i.e. it is not like a restriction enzyme). However, favored and disfavored primary sequences can be detected when many integration sites are aligned. Synthesis and testing of favored HIV integration sites showed that they were favored for integration by PICs in vitro. After a target DNA is bound, the integration reactions take place via a single-step transesterification. Integration of both ends of the viral DNA, followed by melting of the target DNA segments between the points of joining, yields single stranded gaps at each host-virus DNA junction, and a two base overhang derived from the viral DNA. The manner by which this intermediate is subsequently repaired to yield the fully integrated provirus is unclear. For many parasitic DNA replication reactions, the parasite carries out reaction steps only up to a point that the host cannot easily reverse, forcing the host to complete the job (Bushman 2001; Craig et al. 2002). For retroviral integration, it is reasonable to infer that host DNA repair enzymes complete provirus formation. DNA gap repair enzymes are known to be involved in a variety of DNA repair pathways, so their recruitment to gaps at host-virus DNA junctions is readily envisioned. Consistent with this, known gap repair enzymes have been shown to act on model host-virus DNA junctions in vitro (Yoder and Bushman, 2000).
Retroviral integration into minichromosomes in vitro
Gag localization and virus-like particle release mediated by the matrix domain of human T-lymphotropic virus type 1 Gag are less dependent on phosphatidylinositol-(4,5)-bisphosphate than those mediated by the matrix domain of HIV-1 Gag
FUNCTION Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.CATALYTIC ACTIVITY Tetradecanoyl-CoA + glycylpeptide = CoA + N-tetradecanoylglycylpeptide.SIMILARITY Belongs to the NMT family.CAUTION Sequence AAF36406.2 was incorrectly indicated as originating from bovine.
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HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency
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The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM)
HIV Restriction Factors and Mechanisms of Evasion
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MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the ribosomal protein L40e family.SIMILARITY Contains 1 ubiquitin-like domain.
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Alternative splicing: regulation of HIV-1 multiplication as a target for therapeutic action
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MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the ribosomal protein S27Ae family.SIMILARITY Contains 1 ubiquitin-like domain.
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FUNCTION Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation.DISEASE VPS37D is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.SIMILARITY Belongs to the VPS37 family.SIMILARITY Contains 1 VPS37 C-terminal domain.
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HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells
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SIMILARITY Belongs to the archaeal RpoK/eukaryotic RPB6 RNA polymerase subunit family.
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Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus
Gag proteins of the highly replicative MN strain of human immunodeficiency virus type 1: posttranslational modifications, proteolytic processings, and complete amino acid sequences
A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA
A stable complex between integrase and viral DNA ends mediates human immunodeficiency virus integration in vitro
Simian virus 40 minichromosomes as targets for retroviral integration in vivo
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Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition
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SIMILARITY Belongs to the TFIIF alpha subunit family.CAUTION Was reported (PubMed:10428810) to have a protein kinase activity and to autophosphorylates on Ser-385 and Thr-389.
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SIMILARITY Belongs to the VPS28 family.SIMILARITY Contains 1 VPS28 C-terminal domain.SIMILARITY Contains 1 VPS28 N-terminal domain.
HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence
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DNA-directed RNA polymerase II 23 kDa polypeptide (EC 2.7.7.6) (RPB25) (XAP4) (RPB5)
DNA-directed RNA polymerase II 23 kDa polypeptide
DNA-directed RNA polymerase II 7.6 kDa polypeptide
DNA-directed RNA polymerase II 7.6 kDa polypeptide (EC 2.7.7.6) (RPB10) (RPB7.6)
DNA-directed RNA polymerase II 19 kDa polypeptide
DNA-directed RNA polymerase II 14.4 kDa polypeptide (EC 2.7.7.6) (RPB6) (RPB14.4)
DNA-directed RNA polymerase II 14.4 kDa polypeptide
DNA-directed RNA polymerases I, II, and III 17.1 kDa polypeptide
DNA-directed RNA polymerase II 14.5 kDa polypeptide
RNA Pol II (Ser2 phosphorylated) largest subunit
DNA-directed RNA polymerase II largest subunit
DNA-directed RNA polymerases I, II, and III 7.0 kDa polypeptide
DNA-directed RNA polymerase II 140 kDa polypeptide
DNA-directed RNA polymerase II 13.3 kDa polypeptide
Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein
Transcription initiation factor IIF, beta subunit
Transcription initiation factor IIF, alpha subunit
Transcription initiation protein SPT4 homolog 1
Glycosylated Envelope glycoprotein gp160
HIV-1 template:capped HIV-1 transcript hybrid
viral minus strand DNA with sticky 3' end
viral plus strand DNA with sticky 3' end
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The two viral membrane proteins, Env and the accessory protein Vpu, which are encoded by the same mRNA, are translated on the rough ER. All virion components need to traffic from their point of synthesis to sites of assembly on the plasma membrane. Env is an integral membrane protein. It is inserted cotranslationally into ER membranes and then travels through the cellular secretory pathway where it is glycosylated, assembled into trimeric complexes, processed into the gp41 and gp120 subunits by the cellular protease furin.
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Genome-wide analysis of retroviral DNA integration
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SUBUNIT May form pentamers or hexamers. Forms ternary complexes, by interacting with human CD4 and BTRC, and with human BST2 and BTRC.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).SIMILARITY Belongs to the HIV-1 VPU protein family.
SIMILARITY Belongs to the archaeal RpoL/eukaryotic RPB11/RPC19 RNA polymerase subunit family.
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DOMAIN Residues 340-417 are necessary and sufficient for the interaction with HIV-1 IN (IBD domain).DISEASE A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4.SIMILARITY Belongs to the HDGF family.SIMILARITY Contains 1 PWWP domain.
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Domains in the SPT5 protein that modulate its transcriptional regulatory properties
Role of envelope processing and gp41 membrane spanning domain in the formation of human immunodeficiency virus type 1 (HIV-1) fusion-competent envelope glycoprotein complex
SIMILARITY Belongs to the eukaryotic RPB8 RNA polymerase subunit family.
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Distribution and three-dimensional structure of AIDS virus envelope spikes
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Retroviral DNA integration--mechanism and consequences
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FUNCTION HMG-I/Y bind preferentially to the minor groove of A+T rich regions in double-stranded DNA. It is suggested that these proteins could function in nucleosome phasing and in the 3'-end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to A+T-rich regions.SUBUNIT Interacts with HIPK2 (By similarity). Interacts with HIV-1 pre-integration complex.DISEASE A chromosomal aberration involving HMGA1 is found in pulmonary chondroid hamartoma. Translocation t(6;14)(p21;q23-24) with RAD51B.SIMILARITY Belongs to the HMGA family.SIMILARITY Contains 3 A.T hook DNA-binding domains.
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FUNCTION 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 a small RNAs, such as 5S rRNA and tRNAs, respectively.SIMILARITY Belongs to the archaeal RpoP/eukaryotic RPC10 RNA polymerase subunit family.
Symmetrical base preferences surrounding HIV-1, avian sarcoma/leukosis virus, and murine leukemia virus integration sites
Identification of human VPS37C, a component of endosomal sorting complex required for transport-I important for viral budding
CATALYTIC ACTIVITY Release of mature proteins from their proproteins by cleavage of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and vWF from their respective precursors.COFACTOR Calcium.ENZYME REGULATION Could be inhibited by the not secondly cleaved propeptide.TISSUE SPECIFICITY Seems to be expressed ubiquitously.PTM The inhibition peptide, which plays the role of an intramolecular chaperone, is autocatalytically removed in the endoplasmic reticulum (ER) and remains non-covalently bound to furin as a potent autoinhibitor. Following transport to the trans Golgi, a second cleavage within the inhibition propeptide results in propeptide dissociation and furin activation.SIMILARITY Belongs to the peptidase S8 family. Furin subfamily.SIMILARITY Contains 1 homo B/P domain.
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Termination of HIV-1 transcription is believed to be mechanistically the same as termination of endogenous human messages.
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Sequence-specific RNA binding by the HIV-1 Rev protein
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Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75
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Phosphorylated (Ser5) CTD of RNA pol II largest subunit
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Chromosome structure and human immunodeficiency virus type 1 cDNA integration: centromeric alphoid repeats are a disfavored target
A role for LEDGF/p75 in targeting HIV DNA integration
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FUNCTION Escorts unspliced or incompletely spliced viral pre-mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) binds directly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm (By similarity). Interacts with DDX1; the interaction is necessary for proper subcellular localization of this protein.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).SIMILARITY Belongs to the HIV-1 REV protein family.
SIMILARITY Belongs to the archaeal RpoD/eukaryotic RPB3 RNA polymerase subunit family.
SIMILARITY Belongs to the archaeal RpoH/eukaryotic RPB5 RNA polymerase subunit family.
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SIMILARITY Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.
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MISCELLANEOUS This truncated variant has a premature stop codon. It may have arose as a consequence of tissue culture passaging.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).SIMILARITY Belongs to the lentiviruses Tat family.
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SIMILARITY Belongs to the archaeal RpoN/eukaryotic RPB10 RNA polymerase subunit family.
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Nonrandom distribution of gp120 N-linked glycosylation sites important for infectivity of human immunodeficiency virus type 1
DNA-directed RNA polymerase II 33 kDa polypeptide
Wolf-Hirshhorn syndrome candidate 2 protein
DNA-directed RNA polymerase II 16 kDa polypeptide
Retroviral cDNA integration: mechanism, applications and inhibition.(Ed) Setlow JK
Genetic Engineering Principles and Methods 20:41-62
Synthesis, Assembly, and Processing of Viral Proteins
CATALYTIC ACTIVITY Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).MISCELLANEOUS The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion temporarily coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits. The ribonucleoside triphosphate is transferred by a rotation to the nucleotide addition (A) site for pairing with the template DNA. The catalytic A site involves three conserved aspartate residues of the RNA Pol II largest subunit which permanently coordinate a second magnesium ion.SIMILARITY Belongs to the RNA polymerase beta' chain family.
Cumulative mutations of ubiquitin acceptor sites in human immunodeficiency virus type 1 gag cause a late budding defect
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SIMILARITY Belongs to the NELF-A family.SIMILARITY Contains 1 HDAg-like domain.CAUTION PubMed:12612062 has shown that it is not involved in Wolf-Hirschhorn syndrome.
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LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes
Retroviral integration machinery as a probe for DNA structure and associated proteins
Cold Spring Harb Symp Quant Biol 58:533-41
Nucleosomes, DNA-binding proteins, and DNA sequence modulate retroviral integration target site selection
CATALYTIC ACTIVITY [a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate.SIMILARITY Contains 1 BRCT domain.SIMILARITY Contains 1 FCP1 homology domain.
IN bound to sticky 3' ends of viral DNA in PIC
TISSUE SPECIFICITY Ubiquitously expressed.MISCELLANEOUS Interaction between Tat and cyclin-T1 requires zinc.SIMILARITY Belongs to the cyclin family. Cyclin C subfamily.
TISSUE SPECIFICITY Widely expressed. Expressed in colon, brain, heart, kidney, liver, lung, ovary, pancreas, placenta, prostate, skeletal muscle, small intestine, spleen and testis. Not detected in thymus and peripheral blood leukocytes.DOMAIN Has a helix-hairpin-helix (HhH) structural motif conserved among proteins that bind non-specifically to DNA.DOMAIN LEM domain proteins bind centrally on the BAF dimer, whereas DNA binds to the left and right sides.SIMILARITY Belongs to the BAF family.
CATALYTIC ACTIVITY ATP + H(2)O = ADP + phosphate.SIMILARITY Belongs to the TFIIF beta subunit family.
HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer
Identification of an intracellular trafficking and assembly pathway for HIV-1 gag
Synthesis and organization of GAG, GAGPOL polyproteins
Synthesis And Processing Of GAG, GAGPOL Polyproteins
Evidence suggests that the RNA molecules used for the synthesis of Gag and Gag-Pro-Pol are not the same molecules that are packaged into virions. Gag proteins do not appear to aggregate around and capture the RNA contained in the polyribosome from which they emerged, but rather bind to and ultimately encapsidate free transcripts elsewhere. During the replication of retroviruses, large numbers of Gag molecules must be generated to serve as precursors to the structural proteins of the virions. Retroviruses have developed a mechanism that permits expression of the Gag protein at high levels relative to the protein sequences encoded in the pro and pol genes, while retaining coregulated expression. This linkage results from the use of the same initiation codon in the same mRNA to express the gag, pro, and pol genes. Translation of this RNA leads occasionally to synthesis of a fusion protein that is usually called the Gag-Pol precursor but is now more appropriately called the Gag-Pro-Pol precursor
SIMILARITY Belongs to the SPT5 family.SIMILARITY Contains 5 KOW domains.
Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences
MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.SIMILARITY Belongs to the ubiquitin family.SIMILARITY Contains 9 ubiquitin-like domains.
MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS The mRNA encoding variant UBB(+1) is produced by an unknown mechanism involving the deletion of a GT dinucleotide in the close proximity of a GAGAG motif (PubMed:9422699). This variant mRNA is found in normal brain, but the encoded protein accumulates only in brain neurofibrillary tangles and neuritic plaques in Alzheimer disease and other tauopathies, as well as polyglutaminopathies (PubMed:14597671). UBB(+1) variant cannot be used for polyubiquitination, is not effectively degraded by the proteasome when ubiquitinated and ubiquitinated UBB(+1) is refractory to disassembly by deubiquitinating enzymes (DUBs). In healthy brain, UBB(+1) C-terminus can be cleaved by UCHL3 (PubMed:21762696).MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY Belongs to the ubiquitin family.SIMILARITY Contains 3 ubiquitin-like domains.
TISSUE SPECIFICITY Heart, brain, placenta, lung, liver, skeletal, kidney and pancreas.DOMAIN The UEV domain is required for the interaction of the complex with ubiquitin. It also mediates the interaction with PTAP/PSAP motifs of HIV-1 P6 protein and human spumaretrovirus Gag protein.DOMAIN The coiled coil domain may interact with stathmin.DOMAIN The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif independently.PTM Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1. Ubiquitination inactivates it, possibly by regulating its shuttling between an active membrane-bound protein and an inactive soluble form. Ubiquitination by MGRN1 requires the presence of UBE2D1.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.SIMILARITY Contains 1 SB (steadiness box) domain.SIMILARITY Contains 1 UEV (ubiquitin E2 variant) domain.
SIMILARITY Belongs to the NELF-D family.
CATALYTIC ACTIVITY Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).SIMILARITY Belongs to the RNA polymerase beta chain family.
The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore
SIMILARITY Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.SIMILARITY Contains 1 TFIIS-type zinc finger.
MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).SIMILARITY Belongs to the HIV-1 VPR protein family.
INDUCTION Expressed late during infection in a Rev-dependent manner.MISCELLANEOUS Required for replication in 'nonpermissive' cells, including primary T-cells, macrophages and certain T-cell lines, but is dispensable for replication in 'permissive' cell lines, such as 293T cells. In nonpermissive cells, Vif-defective viruses can produce virions, but they fail to complete reverse transcription and cannot successfully infect new cells.MISCELLANEOUS Vif-defective viruses show catastrophic failure in reverse transcription due to APOBEC-induced mutations that initiate a DNA base repair pathway and compromise the structural integrity of the ssDNA. In the absence of Vif, the virion is morphologically abnormal.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).SIMILARITY Belongs to the primate lentivirus group Vif protein family.
A second mammalian N-myristoyltransferase
gene ontology term for cellular function
monoubiquitinated N-myristoyl GAG (P04591) protein
IN:viral DNA bound to host genomic DNA with staggered ends
Assembling Gag molecules are largely derived from the rapidly diffusing cytoplasmic pool. Gag membrane targeting requires myristoylation and a subset of GAG molecules are shuttled to the plasma membrane in this way.
Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex
Monoubiquitinated N-myristoyl Gag polyprotein associates with the ESCRT-1 complex at an endosomal membrane (Eastman et al. 2005; Martin-Serrano et al. 2003; Stuchell et al. 2004).
Monoubiquitination of N-myristoyl GAG polyprotein
Cytosolic N-myristoyl Gag polyprotein is conjugated with a single molecule of ubiquitin. Conjugation is typically to one of two lysine residues in the p6 domain of Gag but can be to lysine residues in the MA, CA, NC, and SP2 domains of the protein. The specific host cell E2 and E3 proteins that mediate Gag ubiquitination have not been identified. The same studies that first identified the p6 ubiquitination sites in Gag also called the biological significance of Gag ubiquitination into question by demonstrating that Gag proteins in which the p6 ubiquitination sites had been removed by mutagenesis could still assemble efficiently into infectious viral particles (Ott et al. 1998, 2000). More recent work, however, has identified additional ubiquitination sites throughout the carboxyterminal region of the Gag polyprotein, and when all of these sites are removed by mutagenesis, both viral assembly involving the mutant Gag polyprotein and infectivity of the resulting viral particles are sharply reduced (Gottwein et al. 2006).