Nuclear receptor-interacting protein 1

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Reviewed, UniProtKB/Swiss-Prot P48552 (NRIP1_HUMAN)

Last modified June 16, 2009. Version 78. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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

Name:

NRIP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	1158 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.

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Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Acetylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	androgen receptor signaling pathway Non-traceable author statement. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Ref.4 Inferred from direct assay. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Ref.1 Ref.4 Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	androgen receptor binding Non-traceable author statement. Source: UniProtKB estrogen receptor binding Ref.1 Inferred from physical interaction. Source: UniProtKB glucocorticoid receptor binding Ref.4 Ref.6 Ref.8 Inferred from physical interaction. Source: UniProtKB transcription coactivator activity Ref.1 Ref.4 Ref.7 Inferred from direct assay. Source: UniProtKB transcription corepressor activity Ref.4 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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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

Required for targeting to small nuclear foci

Region

735 – 885

151

Repression domain 3

Region

1118 – 1158

Repression domain 4

Motif

21 – 25

LXXLL motif 1

Motif

133 – 137

LXXLL motif 2

Motif

185 – 189

LXXLL motif 3

Motif

266 – 270

LXXLL motif 4

Motif

380 – 384

LXXLL motif 5

Motif

440 – 446

CTBP-binding; principal site

Motif

500 – 504

LXXLL motif 6

Motif

565 – 569

CTBP-binding

Motif

599 – 603

CTBP-binding Potential

Motif

713 – 717

LXXLL motif 7

Motif

819 – 823

LXXLL motif 8

Motif

936 – 940

LXXLL motif 9

Motif

946 – 950

CTBP-binding

Motif

1061 – 1074

Ligand-dependent nuclear receptor binding By similarity

Amino acid modifications

Modified residue

104

Phosphoserine By similarity

Modified residue

111

N6-acetyllysine By similarity

Modified residue

158

N6-acetyllysine By similarity

Modified residue

207

Phosphothreonine By similarity

Modified residue

286

N6-acetyllysine By similarity

Modified residue

310

N6-acetyllysine By similarity

Modified residue

356

Phosphoserine By similarity

Modified residue

378

Phosphoserine By similarity

Modified residue

446

N6-acetyllysine Ref.5

Modified residue

481

N6-acetyllysine By similarity

Modified residue

487

Phosphoserine By similarity

Modified residue

518

Phosphoserine By similarity

Modified residue

528

N6-acetyllysine By similarity

Modified residue

542

Phosphoserine By similarity

Modified residue

606

N6-acetyllysine By similarity

Modified residue

671

Phosphoserine By similarity

Modified residue

731

Phosphothreonine Ref.12

Modified residue

931

N6-acetyllysine By similarity

Modified residue

1001

Phosphoserine By similarity

Natural variations

Natural variant

V → I: dbSNP rs9941840.

VAR_051241

Natural variant

221

H → R Ref.14

VAR_023706

Natural variant

315

Y → F: dbSNP rs2228507.

VAR_034142

Natural variant

441

I → V Ref.14

VAR_023707

Natural variant

448

R → G Common polymorphism; associated with endometriosis in a case-control study. dbSNP rs2229742. Ref.1 Ref.14

VAR_023708

Natural variant

567

N → S: dbSNP rs9975169.

VAR_051242

Natural variant

803

S → L Ref.14

VAR_023709

Natural variant

1079

V → F Ref.14

VAR_023710

Experimental info

Mutagenesis

440 – 443

PIDL → AAAA: Abolishes interaction with CTBP1.

Mutagenesis

440 – 442

PID → AIA: Abolishes interaction with CTBP1 and attenuates nuclear hormone receptor-dependent transcription repression.

Mutagenesis

442 – 443

DL → AA: Reduces, but does not completely abolish, interaction with CTBP. Reduces transcriptional repression. Ref.11

Mutagenesis

442 – 443

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

K → Q: Disrupts interaction with CTBP1. Decreases lysine acetylation. Disrupts nuclear hormone receptor-dependent transcription repression. Ref.5

Mutagenesis

446

K → R: Does not disrupt nuclear hormone receptor-dependent transcription repression. Ref.5

Mutagenesis

567 – 568

NL → AA: Disrupts transcriptional repression. Ref.11 Ref.10

Mutagenesis

567 – 568

NL → AS: Disrupts interaction with CTBP1 and CTBP2. Disrupts transcriptional repression; when associated with 442-AS-443. Ref.11 Ref.10

Mutagenesis

599 – 603

SMDLT → PIAAS: Does not further disrupt transcriptional repression; when associated with 442-AA-443 and 567-AA-568.

Mutagenesis

948 – 949

DL → AA: Abolishes CTBP binding but retains transcriptional repressor activity. Ref.10

Sequence conflict

124

P → R in CAA59108. Ref.1

Sequence conflict

721 – 726

NKGKSE → TKGRVK in CAA59108. Ref.1

Sequence conflict

954

S → I in AAH40361. Ref.3

Sequence conflict

1080

T → A in CAA59108. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

P48552-1 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 81FC424968E9A5F6
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FASTA

1,158

126,942

        10         20         30         40         50         60 
MTHGEELGSD VHQDSIVLTY LEGLLMHQAA GGSGTAVDKK SAGHNEEDQN FNISGSAFPT 

        70         80         90        100        110        120 
CQSNGPVLNT HTYQGSGMLH LKKARLLQSS EDWNAAKRKR LSDSIMNLNV KKEALLAGMV 

       130        140        150        160        170        180 
DSVPKGKQDS TLLASLLQSF SSRLQTVALS QQIRQSLKEQ GYALSHDSLK VEKDLRCYGV 

       190        200        210        220        230        240 
ASSHLKTLLK KSKVKDQKPD TNLPDVTKNL IRDRFAESPH HVGQSGTKVM SEPLSCAARL 

       250        260        270        280        290        300 
QAVASMVEKR ASPATSPKPS VACSQLALLL SSEAHLQQYS REHALKTQNA NQAASERLAA 

       310        320        330        340        350        360 
MARLQENGQK DVGSYQLPKG MSSHLNGQAR TSSSKLMASK SSATVFQNPM GIIPSSPKNA 

       370        380        390        400        410        420 
GYKNSLERNN IKQAANNSLL LHLLKSQTIP KPMNGHSHSE RGSIFEESST PTTIDEYSDN 

       430        440        450        460        470        480 
NPSFTDDSSG DESSYSNCVP IDLSCKHRTE KSESDQPVSL DNFTQSLLNT WDPKVPDVDI 

       490        500        510        520        530        540 
KEDQDTSKNS KLNSHQKVTL LQLLLGHKNE ENVEKNTSPQ GVHNDVSKFN TQNYARTSVI 

       550        560        570        580        590        600 
ESPSTNRTTP VSTPPLLTSS KAGSPINLSQ HSLVIKWNSP PYVCSTQSEK LTNTASNHSM 

       610        620        630        640        650        660 
DLTKSKDPPG EKPAQNEGAQ NSATFSASKL LQNLAQCGMQ SSMSVEEQRP SKQLLTGNTD 

       670        680        690        700        710        720 
KPIGMIDRLN SPLLSNKTNA VEENKAFSSQ PTGPEPGLSG SEIENLLERR TVLQLLLGNP 

       730        740        750        760        770        780 
NKGKSEKKEK TPLRDESTQE HSERALSEQI LMVKIKSEPC DDLQIPNTNV HLSHDAKSAP 

       790        800        810        820        830        840 
FLGMAPAVQR SAPALPVSED FKSEPVSPQD FSFSKNGLLS RLLRQNQDSY LADDSDRSHR 

       850        860        870        880        890        900 
NNEMALLESK NLCMVPKKRK LYTEPLENPF KKMKNNIVDA ANNHSAPEVL YGSLLNQEEL 

       910        920        930        940        950        960 
KFSRNDLEFK YPAGHGSASE SEHRSWARES KSFNVLKQLL LSENCVRDLS PHRSNSVADS 

       970        980        990       1000       1010       1020 
KKKGHKNNVT NSKPEFSISS LNGLMYSSTQ PSSCMDNRTF SYPGVVKTPV SPTFPEHLGC 

      1030       1040       1050       1060       1070       1080 
AGSRPESGLL NGCSMPSEKG PIKWVITDAE KNEYEKDSPR LTKTNPILYY MLQKGGNSVT 

      1090       1100       1110       1120       1130       1140 
SRETQDKDIW REASSAESVS QVTAKEELLP TAETKASFFN LRSPYNSHMG NNASRPHSAN 

      1150 
GEVYGLLGSV LTIKKESE

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References

	« Hide 'large scale' referencesShow '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.

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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

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GPO	X-ray	1.95	C	366-390	[»]
2GPP	X-ray	2.60	C/D	366-390	[»]

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...

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Entry information

Entry name

NRIP1_HUMAN

Accession

Primary (citable) accession number: P48552
Secondary accession number(s): Q8IWE8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	December 1, 2000
Last modified:	June 16, 2009
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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