NRIP1_HUMAN
ID NRIP1_HUMAN Reviewed; 1158 AA.
AC P48552; Q8IWE8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Nuclear receptor-interacting protein 1;
DE AltName: Full=Nuclear factor RIP140;
DE AltName: Full=Receptor-interacting protein 140;
GN Name=NRIP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ESR1, SUBCELLULAR
RP LOCATION, AND VARIANT GLY-448.
RC TISSUE=Mammary gland;
RX PubMed=7641693; DOI=10.1002/j.1460-2075.1995.tb00044.x;
RA Cavailles V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P.J.,
RA Parker M.G.;
RT "Nuclear factor RIP140 modulates transcriptional activation by the estrogen
RT receptor.";
RL EMBO J. 14:3741-3751(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH NR2C2.
RX PubMed=9556573; DOI=10.1074/jbc.273.18.10948;
RA Yan Z.H., Karam W.G., Staudinger J.L., Medvedev A., Ghanayem B.I.,
RA Jetten A.M.;
RT "Regulation of peroxisome proliferator-activated receptor alpha-induced
RT transactivation by the nuclear orphan receptor TAK1/TR4.";
RL J. Biol. Chem. 273:10948-10957(1998).
RN [5]
RP FUNCTION, AND INTERACTION WITH NR3C1.
RX PubMed=10364267; DOI=10.1074/jbc.274.25.18121;
RA Subramaniam N., Treuter E., Okret S.;
RT "Receptor interacting protein RIP140 inhibits both positive and negative
RT gene regulation by glucocorticoids.";
RL J. Biol. Chem. 274:18121-18127(1999).
RN [6]
RP FUNCTION, INTERACTION WITH CTBP1, MUTAGENESIS OF 440-PRO--LEU-443 AND
RP LYS-446, AND ACETYLATION AT LYS-446.
RX PubMed=11509661; DOI=10.1128/mcb.21.18.6181-6188.2001;
RA Vo N., Fjeld C., Goodman R.H.;
RT "Acetylation of nuclear hormone receptor-interacting protein RIP140
RT regulates binding of the transcriptional corepressor CtBP.";
RL Mol. Cell. Biol. 21:6181-6188(2001).
RN [7]
RP INTERACTION WITH NR3C1 AND YWHAH, IDENTIFICATION IN A COMPLEX WITH NR3C1
RP AND YWHAH, AND SUBCELLULAR LOCATION.
RX PubMed=11266503; DOI=10.1210/mend.15.4.0624;
RA Zilliacus J., Holter E., Wakui H., Tazawa H., Treuter E., Gustafsson J.-A.;
RT "Regulation of glucocorticoid receptor activity by 14-3-3-dependent
RT intracellular relocalization of the corepressor RIP140.";
RL Mol. Endocrinol. 15:501-511(2001).
RN [8]
RP FUNCTION, AND INTERACTION WITH NR3C2.
RX PubMed=11518808; DOI=10.1210/mend.15.9.0689;
RA Zennaro M.-C., Souque A., Viengchareun S., Poisson E., Lombes M.;
RT "A new human MR splice variant is a ligand-independent transactivator
RT modulating corticosteroid action.";
RL Mol. Endocrinol. 15:1586-1598(2001).
RN [9]
RP INTERACTION WITH NR3C1, AND SUBCELLULAR LOCATION.
RX PubMed=12773562; DOI=10.1128/mcb.23.12.4187-4198.2003;
RA Tazawa H., Osman W., Shoji Y., Treuter E., Gustafsson J.-A., Zilliacus J.;
RT "Regulation of subnuclear localization is associated with a mechanism for
RT nuclear receptor corepression by RIP140.";
RL Mol. Cell. Biol. 23:4187-4198(2003).
RN [10]
RP FUNCTION, AND INTERACTION WITH ESR1; FOS AND JUN.
RX PubMed=12554755; DOI=10.1210/me.2002-0324;
RA Teyssier C., Belguise K., Galtier F., Cavailles V., Chalbos D.;
RT "Receptor-interacting protein 140 binds c-Jun and inhibits estradiol-
RT induced activator protein-1 activity by reversing glucocorticoid receptor-
RT interacting protein 1 effect.";
RL Mol. Endocrinol. 17:287-299(2003).
RN [11]
RP INTERACTION WITH CTBP1 AND CTBP2, MUTAGENESIS OF 442-ASP--LEU-443;
RP 567-ASN--LEU-568 AND 948-ASP--LEU-949, AND IDENTIFICATION OF REPRESSION
RP DOMAINS.
RX PubMed=14736873; DOI=10.1074/jbc.m313906200;
RA Christian M., Tullet J.M.A., Parker M.G.;
RT "Characterization of four autonomous repression domains in the corepressor
RT receptor interacting protein 140.";
RL J. Biol. Chem. 279:15645-15651(2004).
RN [12]
RP FUNCTION, INTERACTION WITH CTBP1; CTBP2; HDAC1; HDAC2; HDAC5 AND HDAC6,
RP MUTAGENESIS OF 442-ASP--LEU-443 AND 567-ASN--LEU-568, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15060175; DOI=10.1093/nar/gkh524;
RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P., Vignon F.,
RA Khochbin S., Jalaguier S., Cavailles V.;
RT "Multiple domains of the receptor-interacting protein 140 contribute to
RT transcription inhibition.";
RL Nucleic Acids Res. 32:1957-1966(2004).
RN [13]
RP INTERACTION WITH NR2C2.
RX PubMed=16887930; DOI=10.1074/mcp.m600180-mcp200;
RA Huq M.D., Gupta P., Tsai N.P., Wei L.N.;
RT "Modulation of testicular receptor 4 activity by mitogen-activated protein
RT kinase-mediated phosphorylation.";
RL Mol. Cell. Proteomics 5:2072-2082(2006).
RN [14]
RP INTERACTION WITH ZNF366.
RX PubMed=17085477; DOI=10.1093/nar/gkl875;
RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M., Jat P.,
RA Kindle K.B., Heery D.M., Parker M.G., Buluwela L., Kamalati T., Ali S.;
RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and
RT histone deacetylases.";
RL Nucleic Acids Res. 34:6126-6136(2006).
RN [15]
RP FUNCTION, INTERACTION WITH RORA, AND INDUCTION.
RX PubMed=21628546; DOI=10.1177/0748730411401579;
RA Poliandri A.H., Gamsby J.J., Christian M., Spinella M.J., Loros J.J.,
RA Dunlap J.C., Parker M.G.;
RT "Modulation of clock gene expression by the transcriptional coregulator
RT receptor interacting protein 140 (RIP140).";
RL J. Biol. Rhythms 26:187-199(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564 AND SER-807, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-671 AND SER-807, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-756 AND LYS-1105, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [19]
RP FUNCTION, AND INVOLVEMENT IN CAKUT3.
RX PubMed=28381549; DOI=10.1681/asn.2016060694;
RA Vivante A., Mann N., Yonath H., Weiss A.C., Getwan M., Kaminski M.M.,
RA Bohnenpoll T., Teyssier C., Chen J., Shril S., van der Ven A.T., Ityel H.,
RA Schmidt J.M., Widmeier E., Bauer S.B., Sanna-Cherchi S., Gharavi A.G.,
RA Lu W., Magen D., Shukrun R., Lifton R.P., Tasic V., Stanescu H.C.,
RA Cavailles V., Kleta R., Anikster Y., Dekel B., Kispert A., Lienkamp S.S.,
RA Hildebrandt F.;
RT "A dominant mutation in nuclear receptor interacting protein 1 causes
RT urinary tract malformations via dysregulation of retinoic acid signaling.";
RL J. Am. Soc. Nephrol. 28:2364-2376(2017).
RN [20]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-111; LYS-170; LYS-195; LYS-198;
RP LYS-372; LYS-508; LYS-756; LYS-802; LYS-850; LYS-901; LYS-931; LYS-1105;
RP LYS-1115 AND LYS-1154, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [21]
RP INVOLVEMENT IN CAKUT3.
RX PubMed=30143558; DOI=10.1681/asn.2017121265;
RA van der Ven A.T., Connaughton D.M., Ityel H., Mann N., Nakayama M.,
RA Chen J., Vivante A., Hwang D.Y., Schulz J., Braun D.A., Schmidt J.M.,
RA Schapiro D., Schneider R., Warejko J.K., Daga A., Majmundar A.J., Tan W.,
RA Jobst-Schwan T., Hermle T., Widmeier E., Ashraf S., Amar A.,
RA Hoogstraaten C.A., Hugo H., Kitzler T.M., Kause F., Kolvenbach C.M.,
RA Dai R., Spaneas L., Amann K., Stein D.R., Baum M.A., Somers M.J.G.,
RA Rodig N.M., Ferguson M.A., Traum A.Z., Daouk G.H., Bogdanovic R.,
RA Stajic N., Soliman N.A., Kari J.A., El Desoky S., Fathy H.M., Milosevic D.,
RA Al-Saffar M., Awad H.S., Eid L.A., Selvin A., Senguttuvan P.,
RA Sanna-Cherchi S., Rehm H.L., MacArthur D.G., Lek M., Laricchia K.M.,
RA Wilson M.W., Mane S.M., Lifton R.P., Lee R.S., Bauer S.B., Lu W.,
RA Reutter H.M., Tasic V., Shril S., Hildebrandt F.;
RT "Whole-exome sequencing identifies causative mutations in families with
RT congenital anomalies of the kidney and urinary tract.";
RL J. Am. Soc. Nephrol. 29:2348-2361(2018).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 366-390 IN COMPLEX WITH ESRRG.
RX PubMed=16990259; DOI=10.1074/jbc.m608410200;
RA Wang L., Zuercher W.J., Consler T.G., Lambert M.H., Miller A.B.,
RA Orband-Miller L.A., McKee D.D., Willson T.M., Nolte R.T.;
RT "X-ray crystal structures of the estrogen-related receptor-gamma ligand
RT binding domain in three functional states reveal the molecular basis of
RT small molecule regulation.";
RL J. Biol. Chem. 281:37773-37781(2006).
RN [23]
RP VARIANTS ARG-221; VAL-441; GLY-448; LEU-803 AND PHE-1079.
RX PubMed=16131398; DOI=10.1186/1743-1050-2-11;
RA Caballero V., Ruiz R., Sainz J.A., Cruz M., Lopez-Nevot M.A., Galan J.J.,
RA Real L.M., de Castro F., Lopez-Villaverde V., Ruiz A.;
RT "Preliminary molecular genetic analysis of the receptor interacting protein
RT 140 (RIP140) in women affected by endometriosis.";
RL J. Exp. Clin. Assist. Reprod. 2:11-11(2005).
CC -!- FUNCTION: Modulates transcriptional activation by steroid receptors
CC such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional
CC repression by nuclear hormone receptors. Positive regulator of the
CC circadian clock gene expression: stimulates transcription of
CC ARNTL/BMAL1, CLOCK and CRY1 by acting as a coactivator for RORA and
CC RORC. Involved in the regulation of ovarian function (By similarity).
CC Plays a role in renal development (PubMed:28381549).
CC {ECO:0000250|UniProtKB:Q8CBD1, ECO:0000269|PubMed:10364267,
CC ECO:0000269|PubMed:11509661, ECO:0000269|PubMed:11518808,
CC ECO:0000269|PubMed:12554755, ECO:0000269|PubMed:15060175,
CC ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:28381549,
CC ECO:0000269|PubMed:7641693}.
CC -!- SUBUNIT: Interacts with RARA and RXRB homodimers and RARA/RXRB
CC heterodimers in the presence of ligand. Interacts with HDAC1 and HDAC3
CC via its N-terminal domain. Interacts with NR2C1 (sumoylated form and
CC via the ligand-binding domain); the interaction results in promoting
CC the repressor activity of NR2C1 (By similarity). Interacts with CTBP1,
CC CTBP2, ESR1, HDAC1, HDAC2, HDAC5, HDAC6, NR2C2, NR3C1, NR3C2, YWHAH,
CC JUN and FOS. Found in a complex with both NR3C1 and YWHAH. Interacts
CC with ZNF366. Interacts with RORA. {ECO:0000250|UniProtKB:Q8CBD1,
CC ECO:0000269|PubMed:10364267, ECO:0000269|PubMed:11266503,
CC ECO:0000269|PubMed:11509661, ECO:0000269|PubMed:11518808,
CC ECO:0000269|PubMed:12554755, ECO:0000269|PubMed:12773562,
CC ECO:0000269|PubMed:14736873, ECO:0000269|PubMed:15060175,
CC ECO:0000269|PubMed:16887930, ECO:0000269|PubMed:16990259,
CC ECO:0000269|PubMed:17085477, ECO:0000269|PubMed:21628546,
CC ECO:0000269|PubMed:7641693, ECO:0000269|PubMed:9556573}.
CC -!- INTERACTION:
CC P48552; O15145: ARPC3; NbExp=3; IntAct=EBI-746484, EBI-351829;
CC P48552; Q6PI77: BHLHB9; NbExp=3; IntAct=EBI-746484, EBI-11519926;
CC P48552; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-746484, EBI-739624;
CC P48552; Q13363: CTBP1; NbExp=3; IntAct=EBI-746484, EBI-908846;
CC P48552; P26358: DNMT1; NbExp=3; IntAct=EBI-746484, EBI-719459;
CC P48552; P62508-3: ESRRG; NbExp=3; IntAct=EBI-746484, EBI-12001340;
CC P48552; Q13642: FHL1; NbExp=6; IntAct=EBI-746484, EBI-912547;
CC P48552; Q08379: GOLGA2; NbExp=3; IntAct=EBI-746484, EBI-618309;
CC P48552; O15379: HDAC3; NbExp=2; IntAct=EBI-746484, EBI-607682;
CC P48552; O95751: LDOC1; NbExp=3; IntAct=EBI-746484, EBI-740738;
CC P48552; Q96KN3: PKNOX2; NbExp=3; IntAct=EBI-746484, EBI-2692890;
CC P48552; Q99873: PRMT1; NbExp=4; IntAct=EBI-746484, EBI-78738;
CC P48552; P10276: RARA; NbExp=4; IntAct=EBI-746484, EBI-413374;
CC P48552; P10276-2: RARA; NbExp=3; IntAct=EBI-746484, EBI-10197061;
CC P48552; Q8N895: ZNF366; NbExp=2; IntAct=EBI-746484, EBI-2813661;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11266503,
CC ECO:0000269|PubMed:12773562, ECO:0000269|PubMed:15060175,
CC ECO:0000269|PubMed:7641693}. Note=Localized to discrete foci and
CC redistributes to larger nuclear domains upon binding to ligand-bound
CC NR3C1.
CC -!- INDUCTION: Expressed in a circadian manner in the liver (at protein
CC level). {ECO:0000269|PubMed:21628546}.
CC -!- DOMAIN: Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have
CC different affinities for nuclear receptors. The C-terminal
CC LTKTNPILYYMLQK motif is required for ligand-dependent interaction with
CC RAAR and RXRB homodimers and heterodimers, for the corepressor
CC activity, and for the formation of an HDAC3 complex with RARA/RXRB (By
CC similarity). Contains at least four autonomous repression domains (RD1-
CC 4). RD1 functions via a histone deacetylase (HDAC)-independent
CC mechanism, whereas RD2, RD3 and RD4 can function by HDAC-dependent or
CC independent mechanisms, depending on cell type. RD2 is dependent on
CC CTBP binding. {ECO:0000250}.
CC -!- PTM: Acetylation regulates its nuclear translocation and corepressive
CC activity (By similarity). Acetylation abolishes interaction with CTBP1.
CC Phosphorylation enhances interaction with YWHAH. {ECO:0000250,
CC ECO:0000269|PubMed:11509661}.
CC -!- DISEASE: Congenital anomalies of kidney and urinary tract 3 (CAKUT3)
CC [MIM:618270]: A disorder encompassing a broad spectrum of renal and
CC urinary tract malformations that include renal agenesis, kidney
CC hypodysplasia, multicystic kidney dysplasia, duplex collecting system,
CC posterior urethral valves and ureter abnormalities. Congenital
CC anomalies of kidney and urinary tract are the commonest cause of
CC chronic kidney disease in children. CAKUT3 inheritance is autosomal
CC dominant. {ECO:0000269|PubMed:28381549, ECO:0000269|PubMed:30143558}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NRIP1ID44067ch21q11.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X84373; CAA59108.1; -; mRNA.
DR EMBL; AF248484; AAF62185.1; -; Genomic_DNA.
DR EMBL; AF127577; AAF35255.1; -; Genomic_DNA.
DR EMBL; AL163207; CAB90396.1; -; Genomic_DNA.
DR EMBL; BC040361; AAH40361.1; -; mRNA.
DR CCDS; CCDS13568.1; -.
DR PIR; S57348; S57348.
DR RefSeq; NP_003480.2; NM_003489.3.
DR RefSeq; XP_005261120.1; XM_005261063.3.
DR RefSeq; XP_005261122.1; XM_005261065.3.
DR RefSeq; XP_011528049.1; XM_011529747.1.
DR RefSeq; XP_011528050.1; XM_011529748.2.
DR RefSeq; XP_011528051.1; XM_011529749.2.
DR RefSeq; XP_011528053.1; XM_011529751.2.
DR RefSeq; XP_011528054.1; XM_011529752.1.
DR RefSeq; XP_016883962.1; XM_017028473.1.
DR RefSeq; XP_016883963.1; XM_017028474.1.
DR RefSeq; XP_016883964.1; XM_017028475.1.
DR RefSeq; XP_016883965.1; XM_017028476.1.
DR PDB; 2GPO; X-ray; 1.95 A; C=366-390.
DR PDB; 2GPP; X-ray; 2.60 A; C/D=366-390.
DR PDB; 4S14; X-ray; 3.54 A; C=499-510.
DR PDB; 4S15; X-ray; 1.90 A; C/D=499-510.
DR PDB; 5NTI; X-ray; 2.40 A; P/Q/R/S=493-512.
DR PDB; 5NTN; X-ray; 1.90 A; P/Q/R/S=493-512.
DR PDB; 5NTW; X-ray; 1.64 A; P/Q/R/S=493-512.
DR PDB; 5NU1; X-ray; 1.85 A; P/Q=493-512.
DR PDB; 6FZU; X-ray; 1.80 A; P/Q=493-512.
DR PDB; 6G05; X-ray; 1.90 A; P/Q=493-512.
DR PDB; 6G07; X-ray; 1.66 A; P/Q/R/S=493-512.
DR PDBsum; 2GPO; -.
DR PDBsum; 2GPP; -.
DR PDBsum; 4S14; -.
DR PDBsum; 4S15; -.
DR PDBsum; 5NTI; -.
DR PDBsum; 5NTN; -.
DR PDBsum; 5NTW; -.
DR PDBsum; 5NU1; -.
DR PDBsum; 6FZU; -.
DR PDBsum; 6G05; -.
DR PDBsum; 6G07; -.
DR AlphaFoldDB; P48552; -.
DR SMR; P48552; -.
DR BioGRID; 113843; 80.
DR DIP; DIP-5964N; -.
DR IntAct; P48552; 30.
DR MINT; P48552; -.
DR STRING; 9606.ENSP00000383063; -.
DR DrugBank; DB06884; 4-HYDROXY-N'-(4-ISOPROPYLBENZYL)BENZOHYDRAZIDE.
DR GlyGen; P48552; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P48552; -.
DR PhosphoSitePlus; P48552; -.
DR BioMuta; NRIP1; -.
DR DMDM; 9988061; -.
DR EPD; P48552; -.
DR jPOST; P48552; -.
DR MassIVE; P48552; -.
DR MaxQB; P48552; -.
DR PaxDb; P48552; -.
DR PeptideAtlas; P48552; -.
DR PRIDE; P48552; -.
DR ProteomicsDB; 55908; -.
DR Antibodypedia; 5789; 238 antibodies from 34 providers.
DR DNASU; 8204; -.
DR Ensembl; ENST00000318948.7; ENSP00000327213.4; ENSG00000180530.11.
DR Ensembl; ENST00000400199.5; ENSP00000383060.1; ENSG00000180530.11.
DR Ensembl; ENST00000400202.5; ENSP00000383063.1; ENSG00000180530.11.
DR GeneID; 8204; -.
DR KEGG; hsa:8204; -.
DR MANE-Select; ENST00000318948.7; ENSP00000327213.4; NM_003489.4; NP_003480.2.
DR UCSC; uc002yjx.2; human.
DR CTD; 8204; -.
DR DisGeNET; 8204; -.
DR GeneCards; NRIP1; -.
DR HGNC; HGNC:8001; NRIP1.
DR HPA; ENSG00000180530; Low tissue specificity.
DR MalaCards; NRIP1; -.
DR MIM; 602490; gene.
DR MIM; 618270; phenotype.
DR neXtProt; NX_P48552; -.
DR OpenTargets; ENSG00000180530; -.
DR PharmGKB; PA31780; -.
DR VEuPathDB; HostDB:ENSG00000180530; -.
DR eggNOG; ENOG502QS1C; Eukaryota.
DR GeneTree; ENSGT00390000007999; -.
DR HOGENOM; CLU_008553_0_0_1; -.
DR InParanoid; P48552; -.
DR OMA; RSGAWND; -.
DR OrthoDB; 345693at2759; -.
DR PhylomeDB; P48552; -.
DR TreeFam; TF332210; -.
DR PathwayCommons; P48552; -.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9029558; NR1H2 & NR1H3 regulate gene expression linked to lipogenesis.
DR Reactome; R-HSA-9632974; NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SignaLink; P48552; -.
DR SIGNOR; P48552; -.
DR BioGRID-ORCS; 8204; 15 hits in 1084 CRISPR screens.
DR ChiTaRS; NRIP1; human.
DR EvolutionaryTrace; P48552; -.
DR GeneWiki; NRIP1; -.
DR GenomeRNAi; 8204; -.
DR Pharos; P48552; Tbio.
DR PRO; PR:P48552; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P48552; protein.
DR Bgee; ENSG00000180530; Expressed in corpus epididymis and 210 other tissues.
DR ExpressionAtlas; P48552; baseline and differential.
DR Genevisible; P48552; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0000118; C:histone deacetylase complex; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:UniProtKB.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IPI:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:UniProtKB.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:BHF-UCL.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0001543; P:ovarian follicle rupture; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR IDEAL; IID00050; -.
DR InterPro; IPR026649; NRIP1.
DR InterPro; IPR031405; NRIP1_RD1.
DR InterPro; IPR031406; NRIP1_RD2.
DR InterPro; IPR031407; NRIP1_RD3.
DR InterPro; IPR031408; NRIP1_RD4.
DR PANTHER; PTHR15088; PTHR15088; 1.
DR Pfam; PF15687; NRIP1_repr_1; 1.
DR Pfam; PF15688; NRIP1_repr_2; 1.
DR Pfam; PF15689; NRIP1_repr_3; 1.
DR Pfam; PF15690; NRIP1_repr_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Biological rhythms; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..1158
FT /note="Nuclear receptor-interacting protein 1"
FT /id="PRO_0000057951"
FT REGION 1..415
FT /note="Interaction with ZNF366"
FT /evidence="ECO:0000269|PubMed:17085477"
FT REGION 33..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..333
FT /note="Repression domain 1"
FT REGION 393..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..700
FT /note="Repression domain 2"
FT REGION 431..472
FT /note="Required for targeting to small nuclear foci"
FT REGION 540..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 592..622
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 641..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 716..745
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 735..885
FT /note="Repression domain 3"
FT REGION 753..1158
FT /note="Interaction with ZNF366"
FT /evidence="ECO:0000269|PubMed:17085477"
FT REGION 950..974
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1118..1158
FT /note="Repression domain 4"
FT MOTIF 21..25
FT /note="LXXLL motif 1"
FT MOTIF 133..137
FT /note="LXXLL motif 2"
FT MOTIF 185..189
FT /note="LXXLL motif 3"
FT MOTIF 266..270
FT /note="LXXLL motif 4"
FT MOTIF 380..384
FT /note="LXXLL motif 5"
FT MOTIF 440..446
FT /note="CTBP-binding; principal site"
FT MOTIF 500..504
FT /note="LXXLL motif 6"
FT MOTIF 565..569
FT /note="CTBP-binding"
FT MOTIF 599..603
FT /note="CTBP-binding"
FT /evidence="ECO:0000255"
FT MOTIF 713..717
FT /note="LXXLL motif 7"
FT MOTIF 819..823
FT /note="LXXLL motif 8"
FT MOTIF 936..940
FT /note="LXXLL motif 9"
FT MOTIF 946..950
FT /note="CTBP-binding"
FT MOTIF 1061..1074
FT /note="Ligand-dependent nuclear receptor binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 404..435
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 641..658
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 722..743
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 954..969
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 111
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 158
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 207
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 286
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 310
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 446
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:11509661"
FT MOD_RES 481
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 528
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 606
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 671
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 807
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 931
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT MOD_RES 1001
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBD1"
FT CROSSLNK 111
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 170
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 195
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 198
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 372
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 508
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 756
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 802
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 850
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 901
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 931
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1105
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1115
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1154
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 37
FT /note="V -> I (in dbSNP:rs9941840)"
FT /id="VAR_051241"
FT VARIANT 221
FT /note="H -> R (in dbSNP:rs139263261)"
FT /evidence="ECO:0000269|PubMed:16131398"
FT /id="VAR_023706"
FT VARIANT 315
FT /note="Y -> F (in dbSNP:rs2228507)"
FT /id="VAR_034142"
FT VARIANT 441
FT /note="I -> V (in dbSNP:rs150468995)"
FT /evidence="ECO:0000269|PubMed:16131398"
FT /id="VAR_023707"
FT VARIANT 448
FT /note="R -> G (in dbSNP:rs2229742)"
FT /evidence="ECO:0000269|PubMed:16131398,
FT ECO:0000269|PubMed:7641693"
FT /id="VAR_023708"
FT VARIANT 567
FT /note="N -> S (in dbSNP:rs9975169)"
FT /id="VAR_051242"
FT VARIANT 803
FT /note="S -> L (in dbSNP:rs61750208)"
FT /evidence="ECO:0000269|PubMed:16131398"
FT /id="VAR_023709"
FT VARIANT 1079
FT /note="V -> F (in dbSNP:rs140803495)"
FT /evidence="ECO:0000269|PubMed:16131398"
FT /id="VAR_023710"
FT MUTAGEN 440..443
FT /note="PIDL->AAAA: Abolishes interaction with CTBP1."
FT /evidence="ECO:0000269|PubMed:11509661"
FT MUTAGEN 440..442
FT /note="PID->AIA: Abolishes interaction with CTBP1 and
FT attenuates nuclear hormone receptor-dependent transcription
FT repression."
FT MUTAGEN 442..443
FT /note="DL->AA: Reduces, but does not completely abolish,
FT interaction with CTBP. Reduces transcriptional repression."
FT /evidence="ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175"
FT MUTAGEN 442..443
FT /note="DL->AS: Disrupts interaction with CTBP1, and CTBP2
FT to a lesser extent. Disrupts transcriptional repression;
FT when associated with 567-AS-568."
FT /evidence="ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175"
FT MUTAGEN 446
FT /note="K->Q: Disrupts interaction with CTBP1. Decreases
FT lysine acetylation. Disrupts nuclear hormone receptor-
FT dependent transcription repression."
FT /evidence="ECO:0000269|PubMed:11509661"
FT MUTAGEN 446
FT /note="K->R: Does not disrupt nuclear hormone receptor-
FT dependent transcription repression."
FT /evidence="ECO:0000269|PubMed:11509661"
FT MUTAGEN 567..568
FT /note="NL->AA: Disrupts transcriptional repression."
FT /evidence="ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175"
FT MUTAGEN 567..568
FT /note="NL->AS: Disrupts interaction with CTBP1 and CTBP2.
FT Disrupts transcriptional repression; when associated with
FT 442-AS-443."
FT /evidence="ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175"
FT MUTAGEN 599..603
FT /note="SMDLT->PIAAS: Does not further disrupt
FT transcriptional repression; when associated with 442-AA-443
FT and 567-AA-568."
FT MUTAGEN 948..949
FT /note="DL->AA: Abolishes CTBP binding but retains
FT transcriptional repressor activity."
FT /evidence="ECO:0000269|PubMed:14736873"
FT CONFLICT 124
FT /note="P -> R (in Ref. 1; CAA59108)"
FT /evidence="ECO:0000305"
FT CONFLICT 721..726
FT /note="NKGKSE -> TKGRVK (in Ref. 1; CAA59108)"
FT /evidence="ECO:0000305"
FT CONFLICT 954
FT /note="S -> I (in Ref. 3; AAH40361)"
FT /evidence="ECO:0000305"
FT CONFLICT 1080
FT /note="T -> A (in Ref. 1; CAA59108)"
FT /evidence="ECO:0000305"
FT HELIX 379..385
FT /evidence="ECO:0007829|PDB:2GPO"
FT HELIX 500..505
FT /evidence="ECO:0007829|PDB:5NTW"
SQ SEQUENCE 1158 AA; 126942 MW; 81FC424968E9A5F6 CRC64;
MTHGEELGSD VHQDSIVLTY LEGLLMHQAA GGSGTAVDKK SAGHNEEDQN FNISGSAFPT
CQSNGPVLNT HTYQGSGMLH LKKARLLQSS EDWNAAKRKR LSDSIMNLNV KKEALLAGMV
DSVPKGKQDS TLLASLLQSF SSRLQTVALS QQIRQSLKEQ GYALSHDSLK VEKDLRCYGV
ASSHLKTLLK KSKVKDQKPD TNLPDVTKNL IRDRFAESPH HVGQSGTKVM SEPLSCAARL
QAVASMVEKR ASPATSPKPS VACSQLALLL SSEAHLQQYS REHALKTQNA NQAASERLAA
MARLQENGQK DVGSYQLPKG MSSHLNGQAR TSSSKLMASK SSATVFQNPM GIIPSSPKNA
GYKNSLERNN IKQAANNSLL LHLLKSQTIP KPMNGHSHSE RGSIFEESST PTTIDEYSDN
NPSFTDDSSG DESSYSNCVP IDLSCKHRTE KSESDQPVSL DNFTQSLLNT WDPKVPDVDI
KEDQDTSKNS KLNSHQKVTL LQLLLGHKNE ENVEKNTSPQ GVHNDVSKFN TQNYARTSVI
ESPSTNRTTP VSTPPLLTSS KAGSPINLSQ HSLVIKWNSP PYVCSTQSEK LTNTASNHSM
DLTKSKDPPG EKPAQNEGAQ NSATFSASKL LQNLAQCGMQ SSMSVEEQRP SKQLLTGNTD
KPIGMIDRLN SPLLSNKTNA VEENKAFSSQ PTGPEPGLSG SEIENLLERR TVLQLLLGNP
NKGKSEKKEK TPLRDESTQE HSERALSEQI LMVKIKSEPC DDLQIPNTNV HLSHDAKSAP
FLGMAPAVQR SAPALPVSED FKSEPVSPQD FSFSKNGLLS RLLRQNQDSY LADDSDRSHR
NNEMALLESK NLCMVPKKRK LYTEPLENPF KKMKNNIVDA ANNHSAPEVL YGSLLNQEEL
KFSRNDLEFK YPAGHGSASE SEHRSWARES KSFNVLKQLL LSENCVRDLS PHRSNSVADS
KKKGHKNNVT NSKPEFSISS LNGLMYSSTQ PSSCMDNRTF SYPGVVKTPV SPTFPEHLGC
AGSRPESGLL NGCSMPSEKG PIKWVITDAE KNEYEKDSPR LTKTNPILYY MLQKGGNSVT
SRETQDKDIW REASSAESVS QVTAKEELLP TAETKASFFN LRSPYNSHMG NNASRPHSAN
GEVYGLLGSV LTIKKESE
