Reviewed,
UniProtKB/Swiss-Prot P48552 (NRIP1_HUMAN)
Last modified
June 16, 2009.
Version 78.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Nuclear receptor-interacting protein 1 Alternative name(s): Nuclear factor RIP140 Receptor-interacting protein 140 | ||
| 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 | 1158 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors. Ref.1 Ref.4 Ref.5 Ref.7 Ref.9 Ref.11 |
| Subunit structure | Interacts with the ligand binding domain (LBD) of NR2C1 in the absence of ligand. Interacts with RARA and RXRB homodimers and RARA/RXRB heterodimers in the presence of ligand. Interacts with HDAC1 and HDAC3 via its N-terminal domain By similarity. Interacts with CTBP1, CTBP2, ESR1, HDAC1, HDAC2, HDAC5, HDAC6, NR3C1, NR3C2, YWHAH, JUN and FOS. Found in a complex with both NR3C1 and YWHAH. |
| Subcellular location | Nucleus. Note: Localized to discrete foci and redistributes to larger nuclear domains upon binding to ligand-bound NR3C1. Ref.1 Ref.11 Ref.6 Ref.8 |
| Domain | Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have different affinities for nuclear receptors. The C-terminal LTKTNPILYYMLQK motif is required for ligand-dependent interaction with RAAR and RXRB homo- and heterodimers, for the corepressor activity, and for the formation of an HDAC3 complex with RARA/RXRB By similarity. Contains at least four autonomous repression domains (RD1-4). RD1 functions via a histone deacetylase (HDAC)-independent mechanism, whereas RD2, RD3 and RD4 can function by HDAC-dependent or independent mechanisms, depending on cell type. RD2 is dependent on CTBP binding. |
| Post-translational modification | Acetylation regulates its nuclear translocation and corepressive activity By similarity. Acetylation abolishes interaction with CTBP1. Phosphorylation enhances interaction with YWHAH. |
| Involvement in disease | Genetic variation in NRIP1 may act as predisposing factor for endometriosis. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1158 | 1158 | Nuclear receptor-interacting protein 1 | PRO_0000057951 | |||||
Regions | |||||||||
| Region | 78 – 333 | 256 | Repression domain 1 | ||||||
| Region | 410 – 700 | 291 | Repression domain 2 | ||||||
| Region | 431 – 472 | 42 | Required for targeting to small nuclear foci | ||||||
| Region | 735 – 885 | 151 | Repression domain 3 | ||||||
| Region | 1118 – 1158 | 41 | Repression domain 4 | ||||||
| Motif | 21 – 25 | 5 | LXXLL motif 1 | ||||||
| Motif | 133 – 137 | 5 | LXXLL motif 2 | ||||||
| Motif | 185 – 189 | 5 | LXXLL motif 3 | ||||||
| Motif | 266 – 270 | 5 | LXXLL motif 4 | ||||||
| Motif | 380 – 384 | 5 | LXXLL motif 5 | ||||||
| Motif | 440 – 446 | 7 | CTBP-binding; principal site | ||||||
| Motif | 500 – 504 | 5 | LXXLL motif 6 | ||||||
| Motif | 565 – 569 | 5 | CTBP-binding | ||||||
| Motif | 599 – 603 | 5 | CTBP-binding Potential | ||||||
| Motif | 713 – 717 | 5 | LXXLL motif 7 | ||||||
| Motif | 819 – 823 | 5 | LXXLL motif 8 | ||||||
| Motif | 936 – 940 | 5 | LXXLL motif 9 | ||||||
| Motif | 946 – 950 | 5 | CTBP-binding | ||||||
| Motif | 1061 – 1074 | 14 | Ligand-dependent nuclear receptor binding By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 104 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 111 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 158 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 207 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 286 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 310 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 356 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 378 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 446 | 1 | N6-acetyllysine Ref.5 | ||||||
| Modified residue | 481 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 487 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 518 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 528 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 542 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 606 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 671 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 731 | 1 | Phosphothreonine Ref.12 | ||||||
| Modified residue | 931 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 1001 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Natural variant | 37 | 1 | V → I: dbSNP rs9941840. | VAR_051241 | |||||
| Natural variant | 221 | 1 | H → R Ref.14 | VAR_023706 | |||||
| Natural variant | 315 | 1 | Y → F: dbSNP rs2228507. | VAR_034142 | |||||
| Natural variant | 441 | 1 | I → V Ref.14 | VAR_023707 | |||||
| Natural variant | 448 | 1 | R → G Common polymorphism; associated with endometriosis in a case-control study. dbSNP rs2229742. Ref.1 Ref.14 | VAR_023708 | |||||
| Natural variant | 567 | 1 | N → S: dbSNP rs9975169. | VAR_051242 | |||||
| Natural variant | 803 | 1 | S → L Ref.14 | VAR_023709 | |||||
| Natural variant | 1079 | 1 | V → F Ref.14 | VAR_023710 | |||||
Experimental info | |||||||||
| Mutagenesis | 440 – 443 | 4 | PIDL → AAAA: Abolishes interaction with CTBP1. | ||||||
| Mutagenesis | 440 – 442 | 3 | PID → AIA: Abolishes interaction with CTBP1 and attenuates nuclear hormone receptor-dependent transcription repression. | ||||||
| Mutagenesis | 442 – 443 | 2 | DL → AA: Reduces, but does not completely abolish, interaction with CTBP. Reduces transcriptional repression. Ref.11 | ||||||
| Mutagenesis | 442 – 443 | 2 | DL → AS: Disrupts interaction with CTBP1, and CTBP2 to a lesser extent. Disrupts transcriptional repression; when associated with 567-AS-568. Ref.11 | ||||||
| Mutagenesis | 446 | 1 | K → Q: Disrupts interaction with CTBP1. Decreases lysine acetylation. Disrupts nuclear hormone receptor-dependent transcription repression. Ref.5 | ||||||
| Mutagenesis | 446 | 1 | K → R: Does not disrupt nuclear hormone receptor-dependent transcription repression. Ref.5 | ||||||
| Mutagenesis | 567 – 568 | 2 | NL → AA: Disrupts transcriptional repression. Ref.11 Ref.10 | ||||||
| Mutagenesis | 567 – 568 | 2 | NL → AS: Disrupts interaction with CTBP1 and CTBP2. Disrupts transcriptional repression; when associated with 442-AS-443. Ref.11 Ref.10 | ||||||
| Mutagenesis | 599 – 603 | 5 | SMDLT → PIAAS: Does not further disrupt transcriptional repression; when associated with 442-AA-443 and 567-AA-568. | ||||||
| Mutagenesis | 948 – 949 | 2 | DL → AA: Abolishes CTBP binding but retains transcriptional repressor activity. Ref.10 | ||||||
| Sequence conflict | 124 | 1 | P → R in CAA59108. Ref.1 | ||||||
| Sequence conflict | 721 – 726 | 6 | NKGKSE → TKGRVK in CAA59108. Ref.1 | ||||||
| Sequence conflict | 954 | 1 | S → I in AAH40361. Ref.3 | ||||||
| Sequence conflict | 1080 | 1 | T → A in CAA59108. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor." Cavailles V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P.J., Parker M.G. EMBO J. 14:3741-3751(1995) [PubMed: 7641693] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ESR1, SUBCELLULAR LOCATION, VARIANT GLY-448. Tissue: Mammary gland. |
| [2] | "The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. Yaspo M.-L.Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin. |
| [4] | "Receptor interacting protein RIP140 inhibits both positive and negative gene regulation by glucocorticoids." Subramaniam N., Treuter E., Okret S. J. Biol. Chem. 274:18121-18127(1999) [PubMed: 10364267] [Abstract] Cited for: FUNCTION, INTERACTION WITH NR3C1. |
| [5] | "Acetylation of nuclear hormone receptor-interacting protein RIP140 regulates binding of the transcriptional corepressor CtBP." Vo N., Fjeld C., Goodman R.H. Mol. Cell. Biol. 21:6181-6188(2001) [PubMed: 11509661] [Abstract] Cited for: FUNCTION, INTERACTION WITH CTBP1, MUTAGENESIS OF 440-PRO--LEU-443 AND LYS-446, ACETYLATION AT LYS-446. |
| [6] | "Regulation of glucocorticoid receptor activity by 14-3-3-dependent intracellular relocalization of the corepressor RIP140." Zilliacus J., Holter E., Wakui H., Tazawa H., Treuter E., Gustafsson J.-A. Mol. Endocrinol. 15:501-511(2001) [PubMed: 11266503] [Abstract] Cited for: INTERACTION WITH NR3C1 AND YWHAH, IDENTIFICATION IN A COMPLEX WITH NR3C1 AND YWHAH, SUBCELLULAR LOCATION. |
| [7] | "A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action." Zennaro M.-C., Souque A., Viengchareun S., Poisson E., Lombes M. Mol. Endocrinol. 15:1586-1598(2001) [PubMed: 11518808] [Abstract] Cited for: FUNCTION, INTERACTION WITH NR3C2. |
| [8] | "Regulation of subnuclear localization is associated with a mechanism for nuclear receptor corepression by RIP140." Tazawa H., Osman W., Shoji Y., Treuter E., Gustafsson J.-A., Zilliacus J. Mol. Cell. Biol. 23:4187-4198(2003) [PubMed: 12773562] [Abstract] Cited for: INTERACTION WITH NR3C1, SUBCELLULAR LOCATION. |
| [9] | "Receptor-interacting protein 140 binds c-Jun and inhibits estradiol-induced activator protein-1 activity by reversing glucocorticoid receptor-interacting protein 1 effect." Teyssier C., Belguise K., Galtier F., Cavailles V., Chalbos D. Mol. Endocrinol. 17:287-299(2003) [PubMed: 12554755] [Abstract] Cited for: FUNCTION, INTERACTION WITH ESR1; FOS AND JUN. |
| [10] | "Characterization of four autonomous repression domains in the corepressor receptor interacting protein 140." Christian M., Tullet J.M.A., Parker M.G. J. Biol. Chem. 279:15645-15651(2004) [PubMed: 14736873] [Abstract] Cited for: INTERACTION WITH CTBP1 AND CTBP2, MUTAGENESIS OF 442-ASP--LEU-443; 567-ASN--LEU-568 AND 948-ASP--LEU-949, IDENTIFICATION OF REPRESSION DOMAINS. |
| [11] | "Multiple domains of the receptor-interacting protein 140 contribute to transcription inhibition." Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P., Vignon F., Khochbin S., Jalaguier S., Cavailles V. Nucleic Acids Res. 32:1957-1966(2004) [PubMed: 15060175] [Abstract] Cited for: FUNCTION, INTERACTION WITH CTBP1; CTBP2; HDAC1; HDAC2; HDAC5 AND HDAC6, MUTAGENESIS OF 442-ASP--LEU-443 AND 567-ASN--LEU-568, SUBCELLULAR LOCATION. |
| [12] | "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-731, MASS SPECTROMETRY. Tissue: Epithelium. |
| [13] | "X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation." Wang L., Zuercher W.J., Consler T.G., Lambert M.H., Miller A.B., Orband-Miller L.A., McKee D.D., Willson T.M., Nolte R.T. J. Biol. Chem. 281:37773-37781(2006) [PubMed: 16990259] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 366-390 IN COMPLEX WITH ESRRG. |
| [14] | "Preliminary molecular genetic analysis of the receptor interacting protein 140 (RIP140) in women affected by endometriosis." Caballero V., Ruiz R., Sainz J.A., Cruz M., Lopez-Nevot M.A., Galan J.J., Real L.M., de Castro F., Lopez-Villaverde V., Ruiz A. J. Exp. Clin. Assist. Reprod. 2:11-11(2005) [PubMed: 16131398] [Abstract] Cited for: VARIANTS ARG-221; VAL-441; GLY-448; LEU-803 AND PHE-1079, INVOLVEMENT IN ENDOMETRIOSIS. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| X84373 mRNA. Translation: CAA59108.1. AF248484 Genomic DNA. Translation: AAF62185.1. AF127577 Genomic DNA. Translation: AAF35255.1. AL163207 Genomic DNA. Translation: CAB90396.1. BC040361 mRNA. Translation: AAH40361.1. | |||||||||||||||||||
| IPI | IPI00010196. | ||||||||||||||||||
| PIR | S57348. | ||||||||||||||||||
| RefSeq | NP_003480.2. | ||||||||||||||||||
| UniGene | Hs.155017 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
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| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| DIP | DIP:5964N. | ||||||||||||||||||
| IntAct | P48552. 6 interactions. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | P48552. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PRIDE | P48552. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENSG00000180530. Homo sapiens. [Contig view] | ||||||||||||||||||
| GeneID | 8204. | ||||||||||||||||||
| KEGG | hsa:8204. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| GeneCards | GC21M015255. | ||||||||||||||||||
| H-InvDB | HIX0027827. | ||||||||||||||||||
| HGNC | HGNC:8001. NRIP1. | ||||||||||||||||||
| MIM | 602490. gene. | ||||||||||||||||||
| PharmGKB | PA31780. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| HOGENOM | P48552. | ||||||||||||||||||
| HOVERGEN | P48552. | ||||||||||||||||||
| OMA | P48552. LLNTWDP. | ||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||
| Pathway_Interaction_DB | ar_pathway. Coregulation of Androgen receptor activity. hnf3apathway. FOXA1 transcription factor network. retinoic_acid_pathway. Retinoic acid receptors-mediated signaling. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | P48552. | ||||||||||||||||||
| Bgee | P48552. | ||||||||||||||||||
| CleanEx | HS_NRIP1. | ||||||||||||||||||
| GermOnline | ENSG00000180530. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other Resources | |||||||||||||||||||
| NextBio | 30914. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | NRIP1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P48552 Secondary accession number(s): Q8IWE8 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 21 Human chromosome 21: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |

Clusters with


