Recombining binding protein suppressor of hairless
Transducin beta-like 1X-related protein 1
F-box-like/WD repeat-containing protein TBL1XR1
F-box-like/WD repeat-containing protein TBL1X
TISSUE SPECIFICITY Expressed in the cochlea.SIMILARITY Belongs to the WD repeat EBI family.SIMILARITY Contains 1 F-box-like domain.SIMILARITY Contains 1 LisH domain.SIMILARITY Contains 8 WD repeats.
A histone deacetylase corepressor complex regulates the Notch signal transduction pathway
A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors
FUNCTION Transcriptional corepressor of NR4A2/NURR1 and acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state (By similarity). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors.SUBUNIT Interacts with BCL6, HDAC7 and C1D. Interacts with NR4A2; this interaction increases in the absence of PITX3 (By similarity). Forms a large corepressor complex that contains SIN3A/B and histone deacetylases HDAC1 and HDAC2. This complex associates with the thyroid (TR) and the retinoid acid receptors (RAR) in the absence of ligand, and may stabilize their interaction with TFIIB. Interacts directly with RARA in the absence of ligand; the interaction represses RARA activity. Interacts (isoform SRMT) with HDAC10. Interacts with MINT. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with CBFA2T3 and ATXN1L. Interacts with RARB; the interaction is weak and does not repress RARB transactivational activity.TISSUE SPECIFICITY Ubiquitous. High levels of expression are detected in lung, spleen and brain.INDUCTION Regulated during cell cycle progression.DOMAIN The N-terminal region contains repression functions that are divided into three independent repression domains (RD1, RD2 and RD3). The C-terminal region contains the nuclear receptor-interacting domains that are divided in two separate interaction domains (ID1 and ID2).DOMAIN The two interaction domains (ID) contain a conserved sequence referred to as the CORNR box. This motif is required and sufficient to permit binding to unligated TR and RARS. Sequences flanking the CORNR box determine nuclear hormone receptor specificity.SIMILARITY Belongs to the N-CoR nuclear receptor corepressors family.SIMILARITY Contains 2 SANT domains.
FUNCTION Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. Functions as a splicing factor in pre-mRNA splicing. Is required in the specific splicing of CDKN1A pre-mRNA; the function probbaly involves the recruitment of U2AF2 to the mRNA. Is proposed to recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA.SUBUNIT Interacts SKI, SMAD2,SMAD3, RBPJ, RB1, PABPN1, MAGEA1, SIRT1, FOXN3, U2AF2, PPIL1, DAXX and ATP1B4. Interacts with VDR and RXRA; preferentially associates with VDR:RXRA heterodimers. Interacts with NCOR2 and EBV EBNA2; NCOR2 and EBV EBNA2 compete for interaction with SNW1. Interacts with MAML1. Interacts with NOTCH1 NICD; the interaction involves multimerized NOTCH1 NICD. Forms a complex with NOTCH1 NICD and MAML1; the association is dissociated by RBPJ. Identified in the spliceosome C complex. Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs). Associates with positive transcription elongation factor b (P-TEFb). Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN. Interacts with human papillomavirus type-16 (HPV16) E7 protein.SIMILARITY Belongs to the SNW family.
FUNCTION Mediates transcriptional repression by certain nuclear receptors. Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors.SUBUNIT Interacts with C1D, SIAH2, HDAC7, SAP30, SIN3A and SIN3B (By similarity). Forms a large corepressor complex that contains. SIN3A/B and histone deacetylases HDAC1 and HDAC2. This complex associates with the thyroid (TR) and the retinoid acid receptors (RAR) in the absence of ligand. Interacts directly with RARA; the interaction is faciliated with RARA trimethylation. Interacts with DACH1. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A and GPS2. Interacts with TRIM28 and KDM3A. Interacts with ZBTB33; the interaction serves to recruit the N-CoR complex to promoter regions containing methylated CpG dinucleotides. Interacts with HDAC9 (via its catalytic domain). Interacts with CBFA2T3 and HEXIM1. Interacts (via the RRFD1 domain) with BAZ1A (via its N-terminal); the interaction corepresses a number of NCOR1-regulated genes.DOMAIN The N-terminal region contains three independent domains that are capable of mediating transcriptional repression (RD1, RD2 and RD3).SIMILARITY Belongs to the N-CoR nuclear receptor corepressors family.SIMILARITY Contains 2 SANT domains.
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SUBUNIT Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1. Notch 1 intracellular domain interacts with SNW1; the interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ. The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation (By similarity). Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A.TISSUE SPECIFICITY In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues.PTM O-glycosylated on the EGF-like domains. Contains both O-linked fucose and O-linked glucose.PTM Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Monoubiquitination at Lys-1759 is required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it. Deubiquitination by EIF3F is necessary for nuclear import of activated Notch.DISEASE Aortic valve disease 1 (AOVD1) [MIM:109730]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry.SIMILARITY Belongs to the NOTCH family.SIMILARITY Contains 5 ANK repeats.SIMILARITY Contains 36 EGF-like domains.SIMILARITY Contains 3 LNR (Lin/Notch) repeats.
SIMILARITY Belongs to the WD repeat EBI family.SIMILARITY Contains 1 F-box-like domain.SIMILARITY Contains 1 LisH domain.SIMILARITY Contains 8 WD repeats.
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TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints
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SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function
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NICD1 displaces NCOR co-repressor complex from CSL
Authored: Egan, SE, Orlic-Milacic, M, 2011-11-14
Interaction of RBPJ (CSL) with NCOR2 (SMRT) was initially discovered in a yeast two-hybrid assay, using human recombinant proteins, and was confirmed in mammalian cells by co-immunoprecipitation of exogenously expressed human RBPJ and NCOR2 from the mouse fibroblast cell line NIH 3T3, as well as by a mammalian two-hybrid assay. These experiments also established, using a RBPJ repression domain mutant, that the repression domain was necessary for interaction with NCOR2 (Kao et al. 1998). Using a mammalian two-hybrid assay, it was found that RBPJ also interacts with NCOR1 in a repression domain dependent way. Over-expression of NCOR2 inhibits transcriptional activity of TAN-1, a gain-of-function NOTCH1 mutant found in T-ALL, through disrupting the interaction of TAN-1 with RBPJ (Kao et al. 1998). NOTCH target genes were found to be de-repressed when cells were treated with TSA (trichostatin A), an inhibitor of HDAC1. HDAC1, known to interact with NCOR2, was found to interact with RBPJ: exogenously expressed human RBPJ co-immunoprecipitated endogenous mouse HDAC1 from CV-1 cell line, derived by from kidney cells of the vervet monkey (also known as the African green monkey, Cercopithecus aethiops or Chlorobus aethiops). The interaction of HDAC1 with RBPJ was dependent on the presence of repression domain (Kao et al. 1998). The recombinant human protein SNW1 (SKIP) was shown to interact with recombinant human RBPJ as part of a transcriptional repression complex, but stays bound to recombinant mouse NICD1 and RBPJ and aids NOTCH-mediated transcription once the NCOR co-repression complex is displaced by NICD1 (Zhou et al. 2000). Mouse Tbl1x and Tbl1xr1 were also found in the NCOR co-repressor complex (Perissi et al. 2004). Once the NCOR complex is displaced, Tbl1x and Tbl1xr1 remain bound to it and facilitate NICD1-mediated transcription probably by acting as adaptors for recruitment of the ubiquitin conjugating/19S proteasome complex that degrades displaced transcriptional repressors (Perissi et al. 2008, Perissi et al. 2004).
FUNCTION Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes. Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively. Specifically binds to the immunoglobulin kappa-type J segment recombination signal sequence. Binds specifically to methylated DNA.SUBUNIT Interacts with activated NOTCH1, NOTCH2 or NOTCH3. Interacts with MINT/SHARP. This interaction may mediate the recruitment of large corepressor complexes containing proteins such as HDAC1, HDAC2, NCOR2, SAP30, FHL1/KYOT2 and CIR1. Interacts with EP300, MAML1 and PTF1A. Interacts with Epstein-Barr virus EBNA2, EBNA3, EBNA4 and EBNA6. Interacts with RITA/C12orf52, leading to nuclear export, prevent the interaction between RBPJ and NICD product and subsequent down-regulation of the Notch signaling pathway. Interacts with SNW1.DISEASE Adams-Oliver syndrome 3 (AOS3) [MIM:614814]: An autosomal dominant form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. AOS3 patients manifest characteristic vertex scalp defects and terminal limb defects, but without congenital heart defects, other associated defects, or immune defects. Note=The disease is caused by mutations affecting the gene represented in this entry.SIMILARITY Belongs to the Su(H) family.SIMILARITY Contains 1 IPT/TIG domain.CAUTION Despite some similarity with the "phage" integrase family, it has no recombinase activity.