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NRIP1 (nuclear receptor interacting protein 1)

Written2009-12Michael J Spinella
Department of Pharmacology, Dartmouth Medical School, 7650 Remsen, Hanover NH 03755, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)RIP140
Other aliasFLJ77253
HGNC (Hugo) NRIP1
LocusID (NCBI) 8204
Atlas_Id 44067
Location 21q11.2  [Link to chromosome band 21q11]
Location_base_pair Starts at 14961235 and ends at 15064805 bp from pter ( according to hg19-Feb_2009)  [Mapping NRIP1.png]
Local_order Cen-GAPDHP16-LOC100128341-NRIP1-CYCSP42-LOC100131399-Tel
Fusion genes
(updated 2016)
NRIP1 (21q11.2) / BTBD1 (15q25.2)NRIP1 (21q11.2) / HIBADH (7p15.2)NRIP1 (21q11.2) / MECOM (3q26.2)
NRIP1 (21q11.2) / SHCBP1 (16q11.2)NRIP1 (21q11.2) / UHRF1 (19p13.3)TIAM1 (21q22.11) / NRIP1 (21q11.2)
UBE2V2 (8q11.21) / NRIP1 (21q11.2)

DNA/RNA

 
Description The gene encompasses approximately 100 Kb and may contain up to 7 exons. The entire protein-coding region is contained within the last exon.
Transcription Transcription is complex. Alternative spliced transcripts containing distinct combinations of 5' non-coding exons occur. Alternative promoters have been described and are proposed to mediate tissue specific expression of RIP140. RIP140 is induced by a number of hormone nuclear receptors including the receptors for estrogen, retinoic acid, androgen, progestins, vitamin D3, peroxisome proliferators-activated receptor-alpha (PPARalpha) and estrogen related receptor-alpha (ERRalpha).
RIP140 mRNA is widely expressed in various tissues and cell types.
Pseudogene None known.

Protein

 
Description RIP140 consists of 1158 amino acids. RIP140 contains ten LXXLL nuclear receptor interaction motifs and four transcriptional repression domains (RD 1-4). RIP140 also contains four c-terminal binding protein (CtBP) interaction motifs. RIP140 activity is regulated by a variety of posttranslational modifications including acetylation, methylation, phosphorylation, sumoylation, and pyridoxal-phosphate (PLP) conjugation.
Expression RIP140 is expressed at low levels in most tissues and is induced in response to hormonal signals. RIP140 is highly expressed in metabolic and reproductive organs and tissues including the liver, adipose tissue, skeletal muscle, ovary and endometrium.
Localisation RIP140 is mainly expressed in the nucleus and contains two putative nuclear localization signals (NLS).
Function RIP140 is a co-repressor of a large number of nuclear receptors. RIP140 interacts preferentially with ligand-bound nuclear receptors and inhibits transactivation by recruitment of histone deacetylases and CtBP. Knockout mice studies revealed that RIP140 has a physiologic role in energy homeostasis, muscle metabolism, adipocyte and hepatocyte function, mitochondrial activity and reproduction. Data suggest that these roles are mediated by RIP140 repression of nuclear receptor mediated gene expression including gene expression mediated by the estrogen receptor, liver X receptor, PPARs, steroidogenic factor 1 (SF1) and ERR.
RIP140 has been shown to regulate retinoic acid mediated differentiation and growth suppression of human embryonal carcinoma cells and the proliferation of breast cancer cells in vitro. A potential role for RIP140 in cancer cachexia has been suggested.
That RIP140 expression can be regulated by multiple nuclear receptors and their ligands and that RIP140 can inhibits the activity of multiple nuclear receptors implies a potential role in the biology of hormone-dependent cancers. This role in cancer is thus far only hypothetical.
Homology RIP140 is highly conserved throughout vertebrates. There is only a single isoform in humans and mice.

Mutations

Note Several synonymous and non-synonymous SNPs have been identified. To date no somatic tumor mutations have been noted.
- Arg448Gly has been associated with endometriosis.
- Gly75Gly has been associated with male infertility.

Implicated in

Note
  
Entity Hormone dependent cancers
Note In a variety of cancer cell culture systems RIP140 has been shown to regulate the activity of a number of nuclear receptors involved in hormone-dependent cancers including estrogen, retinoid, progesterone and androgen receptors.
  
  
Entity Cancer cachexia
Note RIP140 was induced in livers of starved, septic, and tumor-bearing mice. Liver-specific knockdown of RIP140 led to increased hepatic TG release and alleviated hepatic steatosis in tumor-bearing, cachectic animals. RIP140 was found to control the expression of lipid-metabolizing genes in liver.
  
  
Entity Obesity and metabolic disorders
Note RIP140 knockout mice are lean and are resistant to high-fat diet induced obesity. RIP140 regulates genes involved in energy homeostasis in metabolic organs.
  
  
Entity Infertility
Note Female RIP140 knockout mice are infertile due to a defect in ovulation. Also the above-mentioned SNPs have been proposed to be associated with endometriosis and male fertility.
  

Bibliography

Transcriptional regulation of the human NRIP1/RIP140 gene by estrogen is modulated by dioxin signalling.
Augereau P, Badia E, Fuentes M, Rabenoelina F, Corniou M, Derocq D, Balaguer P, Cavailles V.
Mol Pharmacol. 2006 Apr;69(4):1338-46. Epub 2006 Jan 3.
PMID 16391242
 
Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice.
Berriel Diaz M, Krones-Herzig A, Metzger D, Ziegler A, Vegiopoulos A, Klingenspor M, Muller-Decker K, Herzig S.
Hepatology. 2008 Sep;48(3):782-91.
PMID 18712775
 
Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis.
Caballero V, Ruiz R, Sainz JA, Cruz M, Lopez-Nevot MA, Galan JJ, Real LM, de Castro F, Lopez-Villaverde V, Ruiz A
J Exp Clin Assist Reprod. 2005 Aug 30;2:11.
PMID 16131398
 
Genome-wide analysis of estrogen receptor binding sites.
Carroll JS, Meyer CA, Song J, Li W, Geistlinger TR, Eeckhoute J, Brodsky AS, Keeton EK, Fertuck KC, Hall GF, Wang Q, Bekiranov S, Sementchenko V, Fox EA, Silver PA, Gingeras TR, Liu XS, Brown M.
Nat Genet. 2006 Nov;38(11):1289-97. Epub 2006 Oct 1.
PMID 17013392
 
Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor.
Cavailles V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG.
EMBO J. 1995 Aug 1;14(15):3741-51.
PMID 7641693
 
Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype.
Frasor J, Danes JM, Komm B, Chang KC, Lyttle CR, Katzenellenbogen BS.
Endocrinology. 2003 Oct;144(10):4562-74. Epub 2003 Jul 10.
PMID 12040012
 
Multilocus analyses of estrogen-related genes reveal involvement of the ESR1 gene in male infertility and the polygenic nature of the pathology.
Galan JJ, Buch B, Cruz N, Segura A, Moron FJ, Bassas L, Martinez-Pineiro L, Real LM, Ruiz A.
Fertil Steril. 2005 Oct;84(4):910-8.
PMID 16213843
 
Altered progesterone receptor isoform expression remodels progestin responsiveness of breast cancer cells.
Graham JD, Yager ML, Hill HD, Byth K, O'Neill GM, Clarke CL.
Mol Endocrinol. 2005 Nov;19(11):2713-35. Epub 2005 Jun 23.
PMID 15976005
 
Retinoic acid mediates long-paced oscillations in retinoid receptor activity: evidence for a potential role for RIP140.
Heim KC, Gamsby JJ, Hever MP, Freemantle SJ, Loros JJ, Dunlap JC, Spinella MJ.
PLoS One. 2009 Oct 28;4(10):e7639.
PMID 19862326
 
Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells.
Heim KC, White KA, Deng D, Tomlinson CR, Moore JH, Freemantle SJ, Spinella MJ.
Mol Cancer. 2007 Sep 19;6:57.
PMID 17880687
 
The nuclear receptor cofactor, receptor-interacting protein 140, is required for the regulation of hepatic lipid and glucose metabolism by liver X receptor.
Herzog B, Hallberg M, Seth A, Woods A, White R, Parker MG.
Mol Endocrinol. 2007 Nov;21(11):2687-97. Epub 2007 Aug 7.
PMID 17684114
 
Lysine methylation of nuclear co-repressor receptor interacting protein 140.
Huq MD, Ha SG, Barcelona H, Wei LN.
J Proteome Res. 2009 Mar;8(3):1156-67.
PMID 19216533
 
Transcriptional activation of the nuclear receptor corepressor RIP140 by retinoic acid: a potential negative-feedback regulatory mechanism.
Kerley JS, Olsen SL, Freemantle SJ, Spinella MJ.
Biochem Biophys Res Commun. 2001 Jul 27;285(4):969-75.
PMID 11467847
 
Nuclear receptor corepressor RIP140 regulates fat accumulation.
Leonardsson G, Steel JH, Christian M, Pocock V, Milligan S, Bell J, So PW, Medina-Gomez G, Vidal-Puig A, White R, Parker MG.
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8437-42. Epub 2004 May 20.
PMID 15155905
 
Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation.
Lin R, Nagai Y, Sladek R, Bastien Y, Ho J, Petrecca K, Sotiropoulou G, Diamandis EP, Hudson TJ, White JH.
Mol Endocrinol. 2002 Jun;16(6):1243-56.
PMID 12040012
 
Post-translational modifications of nuclear co-repressor RIP140: a therapeutic target for metabolic diseases.
Mostaqul Huq MD, Gupta P, Wei LN.
Curr Med Chem. 2008;15(4):386-92. (REVIEW)
PMID 18288993
 
RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis.
Nichol D, Christian M, Steel JH, White R, Parker MG.
J Biol Chem. 2006 Oct 27;281(43):32140-7. Epub 2006 Aug 21.
PMID 16923809
 
Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes.
Powelka AM, Seth A, Virbasius JV, Kiskinis E, Nicoloro SM, Guilherme A, Tang X, Straubhaar J, Cherniack AD, Parker MG, Czech MP.
J Clin Invest. 2006 Jan;116(1):125-36. Epub 2005 Dec 22.
PMID 16374519
 
SUMOylation modulates the transcription repressor function of RIP140.
Rytinki MM, Palvimo JJ.
J Biol Chem. 2008 Apr 25;283(17):11586-95. Epub 2008 Jan 22.
PMID 18211901
 
The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle.
Seth A, Steel JH, Nichol D, Pocock V, Kumaran MK, Fritah A, Mobberley M, Ryder TA, Rowlerson A, Scott J, Poutanen M, White R, Parker M.
Cell Metab. 2007 Sep;6(3):236-45.
PMID 17767910
 
Acetylation of nuclear hormone receptor-interacting protein RIP140 regulates binding of the transcriptional corepressor CtBP.
Vo N, Fjeld C, Goodman RH.
Mol Cell Biol. 2001 Sep;21(18):6181-8.
PMID 11509661
 
Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing.
Wei LN, Hu X, Chandra D, Seto E, Farooqui M.
J Biol Chem. 2000 Dec 29;275(52):40782-7.
PMID 11006275
 
Limiting effects of RIP140 in estrogen signaling: potential mediation of anti-estrogenic effects of retinoic acid.
White KA, Yore MM, Deng D, Spinella MJ.
J Biol Chem. 2005 Mar 4;280(9):7829-35. Epub 2005 Jan 4.
PMID 15632153
 
The nuclear receptor co-repressor nrip1 (RIP140) is essential for female fertility.
White R, Leonardsson G, Rosewell I, Ann Jacobs M, Milligan S, Parker M.
Nat Med. 2000 Dec;6(12):1368-74.
PMID 11100122
 
Role of RIP140 in metabolic tissues: connections to disease.
White R, Morganstein D, Christian M, Seth A, Herzog B, Parker MG.
FEBS Lett. 2008 Jan 9;582(1):39-45. Epub 2007 Nov 20. (REVIEW)
PMID 18023280
 

Citation

This paper should be referenced as such :
Spinella, MJ
NRIP1 (nuclear receptor interacting protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):923-925.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NRIP1ID44067ch21q11.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;21)(q26;q11) NRIP1/MECOM


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Squamous Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)NRIP1   8001
Cards
AtlasNRIP1ID44067ch21q11
Entrez_Gene (NCBI)NRIP1  8204  nuclear receptor interacting protein 1
AliasesRIP140
GeneCards (Weizmann)NRIP1
Ensembl hg19 (Hinxton)ENSG00000180530 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000180530 [Gene_View]  chr21:14961235-15064805 [Contig_View]  NRIP1 [Vega]
ICGC DataPortalENSG00000180530
TCGA cBioPortalNRIP1
AceView (NCBI)NRIP1
Genatlas (Paris)NRIP1
WikiGenes8204
SOURCE (Princeton)NRIP1
Genetics Home Reference (NIH)NRIP1
Genomic and cartography
GoldenPath hg38 (UCSC)NRIP1  -     chr21:14961235-15064805 -  21q11.2-q21.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)NRIP1  -     21q11.2-q21.1   [Description]    (hg19-Feb_2009)
EnsemblNRIP1 - 21q11.2-q21.1 [CytoView hg19]  NRIP1 - 21q11.2-q21.1 [CytoView hg38]
Mapping of homologs : NCBINRIP1 [Mapview hg19]  NRIP1 [Mapview hg38]
OMIM602490   
Gene and transcription
Genbank (Entrez)AK123818 AK289786 BC040361 BE792046 DQ891180
RefSeq transcript (Entrez)NM_003489
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)NRIP1
Cluster EST : UnigeneHs.155017 [ NCBI ]
CGAP (NCI)Hs.155017
Alternative Splicing GalleryENSG00000180530
Gene ExpressionNRIP1 [ NCBI-GEO ]   NRIP1 [ EBI - ARRAY_EXPRESS ]   NRIP1 [ SEEK ]   NRIP1 [ MEM ]
Gene Expression Viewer (FireBrowse)NRIP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8204
GTEX Portal (Tissue expression)NRIP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP48552   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP48552  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP48552
Splice isoforms : SwissVarP48552
PhosPhoSitePlusP48552
Domains : Interpro (EBI)NRIP1    NRIP1_RD1    NRIP1_RD2    NRIP1_RD3    NRIP1_RD4   
Domain families : Pfam (Sanger)NRIP1_repr_1 (PF15687)    NRIP1_repr_2 (PF15688)    NRIP1_repr_3 (PF15689)    NRIP1_repr_4 (PF15690)   
Domain families : Pfam (NCBI)pfam15687    pfam15688    pfam15689    pfam15690   
Conserved Domain (NCBI)NRIP1
DMDM Disease mutations8204
Blocks (Seattle)NRIP1
PDB (SRS)2GPO    2GPP    4S14    4S15   
PDB (PDBSum)2GPO    2GPP    4S14    4S15   
PDB (IMB)2GPO    2GPP    4S14    4S15   
PDB (RSDB)2GPO    2GPP    4S14    4S15   
Structural Biology KnowledgeBase2GPO    2GPP    4S14    4S15   
SCOP (Structural Classification of Proteins)2GPO    2GPP    4S14    4S15   
CATH (Classification of proteins structures)2GPO    2GPP    4S14    4S15   
SuperfamilyP48552
Human Protein AtlasENSG00000180530
Peptide AtlasP48552
HPRD03927
IPIIPI00010196   IPI00795603   
Protein Interaction databases
DIP (DOE-UCLA)P48552
IntAct (EBI)P48552
FunCoupENSG00000180530
BioGRIDNRIP1
STRING (EMBL)NRIP1
ZODIACNRIP1
Ontologies - Pathways
QuickGOP48552
Ontology : AmiGOhistone deacetylase complex  negative regulation of transcription from RNA polymerase II promoter  nuclear chromatin  core promoter sequence-specific DNA binding  ovarian follicle rupture  transcription coactivator activity  transcription coactivator activity  transcription corepressor activity  protein binding  nucleus  nucleolus  transcription, DNA-templated  circadian rhythm  nuclear speck  lipid storage  estrogen receptor binding  androgen receptor signaling pathway  circadian regulation of gene expression  nuclear hormone receptor binding  glucocorticoid receptor binding  histone deacetylase binding  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  retinoid X receptor binding  androgen receptor binding  cellular response to estradiol stimulus  
Ontology : EGO-EBIhistone deacetylase complex  negative regulation of transcription from RNA polymerase II promoter  nuclear chromatin  core promoter sequence-specific DNA binding  ovarian follicle rupture  transcription coactivator activity  transcription coactivator activity  transcription corepressor activity  protein binding  nucleus  nucleolus  transcription, DNA-templated  circadian rhythm  nuclear speck  lipid storage  estrogen receptor binding  androgen receptor signaling pathway  circadian regulation of gene expression  nuclear hormone receptor binding  glucocorticoid receptor binding  histone deacetylase binding  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  retinoid X receptor binding  androgen receptor binding  cellular response to estradiol stimulus  
Pathways : BIOCARTACARM1 and Regulation of the Estrogen Receptor [Genes]    Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]   
REACTOMEP48552 [protein]
REACTOME PathwaysR-HSA-400253 [pathway]   
NDEx NetworkNRIP1
Atlas of Cancer Signalling NetworkNRIP1
Wikipedia pathwaysNRIP1
Orthology - Evolution
OrthoDB8204
GeneTree (enSembl)ENSG00000180530
Phylogenetic Trees/Animal Genes : TreeFamNRIP1
HOVERGENP48552
HOGENOMP48552
Homologs : HomoloGeneNRIP1
Homology/Alignments : Family Browser (UCSC)NRIP1
Gene fusions - Rearrangements
Fusion : MitelmanNRIP1/HIBADH [21q11.2/7p15.2]  
Fusion : MitelmanNRIP1/MECOM [21q11.2/3q26.2]  [t(3;21)(q26;q21)]  
Fusion : MitelmanNRIP1/SHCBP1 [21q11.2/16q11.2]  [t(16;21)(q11;q21)]  
Fusion : MitelmanTIAM1/NRIP1 [21q22.11/21q11.2]  [t(21;21)(q21;q22)]  
Fusion : MitelmanUBE2V2/NRIP1 [8q11.21/21q11.2]  [t(8;21)(q11;q21)]  
Fusion: TCGANRIP1 21q11.2 HIBADH 7p15.2 BRCA
Fusion: TCGANRIP1 21q11.2 SHCBP1 16q11.2 BRCA
Fusion: TCGATIAM1 21q22.11 NRIP1 21q11.2 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNRIP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)NRIP1
dbVarNRIP1
ClinVarNRIP1
1000_GenomesNRIP1 
Exome Variant ServerNRIP1
ExAC (Exome Aggregation Consortium)NRIP1 (select the gene name)
Genetic variants : HAPMAP8204
Genomic Variants (DGV)NRIP1 [DGVbeta]
DECIPHERNRIP1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisNRIP1 
Mutations
ICGC Data PortalNRIP1 
TCGA Data PortalNRIP1 
Broad Tumor PortalNRIP1
OASIS PortalNRIP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICNRIP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDNRIP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch NRIP1
DgiDB (Drug Gene Interaction Database)NRIP1
DoCM (Curated mutations)NRIP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)NRIP1 (select a term)
intoGenNRIP1
NCG5 (London)NRIP1
Cancer3DNRIP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602490   
Orphanet
MedgenNRIP1
Genetic Testing Registry NRIP1
NextProtP48552 [Medical]
TSGene8204
GENETestsNRIP1
Target ValidationNRIP1
Huge Navigator NRIP1 [HugePedia]
snp3D : Map Gene to Disease8204
BioCentury BCIQNRIP1
ClinGenNRIP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8204
Chemical/Pharm GKB GenePA31780
Clinical trialNRIP1
Miscellaneous
canSAR (ICR)NRIP1 (select the gene name)
Probes
Litterature
PubMed116 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineNRIP1
EVEXNRIP1
GoPubMedNRIP1
iHOPNRIP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon May 22 09:18:30 CEST 2017

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