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UniProtKB/Swiss-Prot O75376 (NCOR1_HUMAN)
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November 25, 2008.
Version 90.
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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: Nuclear receptor corepressor 1 Short name=N-CoR1 Short name=N-CoR | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 2440 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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 structure | Interacts with 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 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 MJD2A/JHDM3A. Interacts with ZBTB33/KAISO, and this interaction serves to recruit the N-CoR complex to promoter regions containing methylated CpG dinucleotides. Interacts with the catalytic domain of HDAC9. Interacts with CBFA2T3 and HEXIM1. Interacts with C1D By similarity. |
| Subcellular location | NucleusBy similarity. |
| Domain | The N-terminal region contains three independent domains that are capable of mediating transcriptional repression (RD1, RD2 and RD3). The C-terminal region contains two separate nuclear receptor-interacting domains (ID1 and ID2), each of which contains a conserved sequence referred to as the CORNR box. This motif is necessary and sufficient for binding to unligated nuclear hormone receptors, while sequences flanking the CORNR box determine the precise nuclear hormone receptor specificity By similarity. |
| Post-translational modification | Ubiquitinated; mediated by SIAH2 and leading to its subsequent proteasomal degradation By similarity. |
| Sequence similarities | Belongs to the N-CoR nuclear receptor corepressors family. Contains 2 SANT domains. |
Ontologies
Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Nucleus |
| Coding sequence diversity | Alternative splicing |
| Domain | Coiled coil Repeat |
| Ligand | DNA-binding |
| Molecular function | Chromatin regulator Repressor |
| PTM | Phosphoprotein Ubl conjugation |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Biological process | chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependentInferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoterTraceable author statement. Source: ProtInc |
| Cellular component | nucleus Inferred from electronic annotation. Source: UniProtKB-KW |
| Molecular function | DNA binding Inferred from electronic annotation. Source: InterPro transcription corepressor activityTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| DACH1 | Q9UI36 | 2 | EBI-347233,EBI-347111 | |
| HDAC9 | Q9UKV0 | 1 | EBI-347233,EBI-765444 | |
| RDBP | P18615 | 1 | EBI-347233,EBI-348444 | |
| SKI | P12755 | 1 | EBI-347233,EBI-347281 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O75376-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: O75376-2) The sequence of this isoform differs from the canonical sequence as follows: 727-727: E → EGAENSSDTESAPSPSP 1842-1961: SKHEAARLEE...SQSSDSSSSL → I | ||||||
| Notes: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2440 | 2440 | Nuclear receptor corepressor 1 | PRO_0000055617 | |||||
Regions | |||||||||
| Domain | 435 – 486 | 52 | SANT 1 | ||||||
| Domain | 623 – 674 | 52 | SANT 2 | ||||||
| Region | 1 – 373 | 373 | Interaction with ZBTB33 and HEXIM1 | ||||||
| Region | 254 – 312 | 59 | Interaction with SIN3A/B | ||||||
| Region | 988 – 1816 | 829 | Interaction with ETO | ||||||
| Region | 1501 – 2440 | 940 | Interaction with C1D By similarity | ||||||
| Region | 2032 – 2115 | 84 | ID1 By similarity | ||||||
| Region | 2212 – 2273 | 62 | ID2 By similarity | ||||||
| Coiled coil | 174 – 216 | 43 | Potential | ||||||
| Coiled coil | 299 – 328 | 30 | Potential | ||||||
| Coiled coil | 501 – 557 | 57 | Potential | ||||||
| Motif | 1933 – 1937 | 5 | CORNR box 1 | ||||||
| Motif | 2055 – 2059 | 5 | CORNR box 2 | ||||||
| Motif | 2263 – 2267 | 5 | CORNR box 3 | ||||||
| Compositional bias | 58 – 64 | 7 | Poly-Gln | ||||||
| Compositional bias | 593 – 603 | 11 | Poly-Ala | ||||||
| Compositional bias | 607 – 617 | 11 | Pro-rich | ||||||
| Compositional bias | 1032 – 1035 | 4 | Poly-Pro | ||||||
| Compositional bias | 1707 – 1712 | 6 | Poly-Ala | ||||||
| Compositional bias | 1952 – 1963 | 12 | Poly-Ser | ||||||
Amino acid modifications | |||||||||
| Modified residue | 158 | 1 | Phosphoserine | ||||||
| Modified residue | 172 | 1 | Phosphoserine | ||||||
| Modified residue | 224 | 1 | Phosphoserine | ||||||
| Modified residue | 999 | 1 | Phosphoserine | ||||||
| Modified residue | 1450 | 1 | Phosphoserine | ||||||
| Modified residue | 1472 | 1 | Phosphoserine | ||||||
| Modified residue | 1977 | 1 | Phosphoserine | ||||||
| Modified residue | 2120 | 1 | Phosphoserine | ||||||
| Modified residue | 2151 | 1 | Phosphoserine | ||||||
| Modified residue | 2184 | 1 | Phosphoserine | ||||||
| Modified residue | 2432 | 1 | Phosphotyrosine | ||||||
| Modified residue | 2434 | 1 | Phosphothreonine | ||||||
| Modified residue | 2436 | 1 | Phosphoserine | ||||||
| Modified residue | 2438 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Alternative sequence | 727 | 1 | E → EGAENSSDTESAPSPSP in isoform 2. | VSP_010207 | |||||
| Alternative sequence | 1842 – 1961 | 120 | SKHEA…SSSSL → I in isoform 2. | VSP_010208 | |||||
Experimental info | |||||||||
| Sequence conflict | 1014 | 1 | V → L in AAC33550. Ref.1 | ||||||
| Sequence conflict | 1508 – 1509 | 2 | SS → PP in AAC33550. Ref.1 | ||||||
| Sequence conflict | 1561 | 1 | R → W in AAC33550. Ref.1 | ||||||
| Sequence conflict | 1567 | 1 | H → Q in AAC33550. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex." Wang J., Hoshino T., Redner R.L., Kajigaya S., Liu J.M. Proc. Natl. Acad. Sci. U.S.A. 95:10860-10865(1998) [PubMed: 9724795] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain. |
| [2] | "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed: 10470851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [3] | Ohara O., Nagase T., Kikuno R. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. |
| [4] | "Localization of the human nuclear receptor co-repressor (hN-CoR) gene between the CMT1A and the SMS critical regions of chromosome 17p11.2." Nagaya T., Chen K.-S., Fujieda M., Ohmori S., Richer J.K., Horwitz K.B., Lupski J.R., Seo H. Genomics 59:339-341(1999) [PubMed: 10444336] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 974-2440 (ISOFORM 1). |
| [5] | "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1." Underhill C., Qutob M.S., Yee S.P., Torchia J. J. Biol. Chem. 275:40463-40470(2000) [PubMed: 11013263] [Abstract] Cited for: INTERACTION WITH TRIM28. |
| [6] | "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain." Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W. Mol. Cell. Biol. 21:6470-6483(2001) [PubMed: 11533236] [Abstract] Cited for: INTERACTION WITH CBFA2T3. |
| [7] | "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2." Zhang J., Kalkum M., Chait B.T., Roeder R.G. Mol. Cell 9:611-623(2002) [PubMed: 11931768] [Abstract] Cited for: COMPONENT OF THE N-COR COMPLEX WITH TBL1X; TBL1R; NCOR2; GPS2 AND HDAC3. |
| [8] | "The histone deacetylase 9 gene encodes multiple protein isoforms." Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., Zelent A. J. Biol. Chem. 278:16059-16072(2003) [PubMed: 12590135] [Abstract] Cited for: INTERACTION WITH HDAC9. |
| [9] | "DACH1 inhibits transforming growth factor-beta signaling through binding Smad4." Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K., Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G. J. Biol. Chem. 278:51673-51684(2003) [PubMed: 14525983] [Abstract] Cited for: INTERACTION WITH DACH1. |
| [10] | "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso." Yoon H.-G., Chan D.W., Reynolds A.B., Qin J., Wong J. Mol. Cell 12:723-734(2003) [PubMed: 14527417] [Abstract] Cited for: FUNCTION, INTERACTION WITH CORO2A; GPS2; HDAC3; TBL1R; TBL1X AND ZBTB33. |
| [11] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158; SER-172; SER-1977; SER-2120 AND SER-2184, MASS SPECTROMETRY. Tissue: Epithelium. |
| [12] | "JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2)." Zhang D., Yoon H.-G., Wong J. Mol. Cell. Biol. 25:6404-6414(2005) [PubMed: 16024779] [Abstract] Cited for: INTERACTION WITH JMJD2A. |
| [13] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-224; SER-999; SER-2151; TYR-2432; THR-2434; SER-2436 AND SER-2438, MASS SPECTROMETRY. Tissue: Epithelium. |
| [14] | "A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2120 AND SER-2184, MASS SPECTROMETRY. Tissue: Epithelium. |
| [15] | "Regulation of P-TEFb elongation complex activity by CDK9 acetylation." Fu J., Yoon H.-G., Qin J., Wong J. Mol. Cell. Biol. 27:4641-4651(2007) [PubMed: 17452463] [Abstract] Cited for: INTERACTION WITH HEXIM1. |
| [16] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1450 AND SER-1472, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AF044209 mRNA. Translation: AAC33550.1. AB028970 mRNA. Translation: BAA82999.2. Different initiation. AB019524 mRNA. Translation: BAA75814.1. | |||||||||||||
| RefSeq | NP_006302.2. | ||||||||||||
| UniGene | Hs.462323 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| SMR | O75376. Positions 421-488. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | O75376. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | O75376. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000141027. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 9611. | ||||||||||||
| KEGG | hsa:9611. | ||||||||||||
Organism-specific databases | |||||||||||||