Wikipedia

NRIP1

Jedarni receptor-interaktivni protein 1 (NRIP1), znan i kao receptor-interaktivni protein 140 (RIP140) jest protein koji je kod ljudi kodiran genom NRIP1 sa hromosoma 21.[5][6]

NRIP1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2GPO, 2GPP, 4S14, 4S15

Identifikatori
AliasiNRIP1
Vanjski ID-jeviOMIM: 602490 MGI: 1315213 HomoloGene: 2606 GeneCards: NRIP1
Lokacija gena (čovjek)
Hromosom 21 (čovjek)
Hrom.Hromosom 21 (čovjek)[1]
Hromosom 21 (čovjek)
Genomska lokacija za NRIP1
Genomska lokacija za NRIP1
Bend21q11.2-q21.1Početak14,961,235 bp[1]
Kraj15,065,936 bp[1]
Lokacija gena (miš)
Hromosom 16 (miš)
Hrom.Hromosom 16 (miš)[2]
Hromosom 16 (miš)
Genomska lokacija za NRIP1
Genomska lokacija za NRIP1
Bend16|16 C3.1Početak76,084,288 bp[2]
Kraj76,170,715 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• glucocorticoid receptor binding
• signaling receptor binding
• GO:0001104 transcription coregulator activity
• retinoid X receptor binding
• histone deacetylase binding
• androgen receptor binding
• core promoter sequence-specific DNA binding
• retinoic acid receptor binding
• GO:0001948, GO:0016582 vezivanje za proteine
• GO:0001106 transcription corepressor activity
• GO:0001105 transcription coactivator activity
• estrogen receptor binding
• GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Ćelijska komponenta• Jedarce
• histone deacetylase complex
• nuclear speck
• jedro
• nukleoplazma
Biološki proces• rhythmic process
• transcription, DNA-templated
• Ovulacija
• GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II
• lipid storage
• androgen receptor signaling pathway
• GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
• cellular response to estradiol stimulus
• GO:0009373 regulation of transcription, DNA-templated
• GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
• ovarian follicle rupture
• circadian regulation of gene expression
• GO:1901227 negative regulation of transcription by RNA polymerase II
• Jednodnevni biološki ritam
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

8204

268903

Ensembl

ENSG00000180530

ENSMUSG00000048490

UniProt

P48552

Q8CBD1

RefSeq (mRNK)

NM_003489

NM_173440
NM_001358238

RefSeq (bjelančevina)

NP_003480

NP_775616
NP_001345167

Lokacija (UCSC)Chr 21: 14.96 – 15.07 MbChr 16: 76.08 – 76.17 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš
Jedarnu receptor-intersktivni proteinski 1 represije 1
Identifikatori
SimbolNRIP1 repr-1
Jedarni receptor-interaktivni protein 1 represije 2
Identifikatori
SimbolNRIP1-repr-2
Jedarni receptor-interaktivni protein 1 represije 3
Identifikatori
SimbolNRIP1-repr-3
Jedarmi receptor-interaktivni protein 1 represije 4
Identifikatori
SimbolNRIP1-repr-4

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 1.158 aminokiselina, a molekulska težina 126.942 Da.[7]

1020304050
MTHGEELGSDVHQDSIVLTYLEGLLMHQAAGGSGTAVDKKSAGHNEEDQN
FNISGSAFPTCQSNGPVLNTHTYQGSGMLHLKKARLLQSSEDWNAAKRKR
LSDSIMNLNVKKEALLAGMVDSVPKGKQDSTLLASLLQSFSSRLQTVALS
QQIRQSLKEQGYALSHDSLKVEKDLRCYGVASSHLKTLLKKSKVKDQKPD
TNLPDVTKNLIRDRFAESPHHVGQSGTKVMSEPLSCAARLQAVASMVEKR
ASPATSPKPSVACSQLALLLSSEAHLQQYSREHALKTQNANQAASERLAA
MARLQENGQKDVGSYQLPKGMSSHLNGQARTSSSKLMASKSSATVFQNPM
GIIPSSPKNAGYKNSLERNNIKQAANNSLLLHLLKSQTIPKPMNGHSHSE
RGSIFEESSTPTTIDEYSDNNPSFTDDSSGDESSYSNCVPIDLSCKHRTE
KSESDQPVSLDNFTQSLLNTWDPKVPDVDIKEDQDTSKNSKLNSHQKVTL
LQLLLGHKNEENVEKNTSPQGVHNDVSKFNTQNYARTSVIESPSTNRTTP
VSTPPLLTSSKAGSPINLSQHSLVIKWNSPPYVCSTQSEKLTNTASNHSM
DLTKSKDPPGEKPAQNEGAQNSATFSASKLLQNLAQCGMQSSMSVEEQRP
SKQLLTGNTDKPIGMIDRLNSPLLSNKTNAVEENKAFSSQPTGPEPGLSG
SEIENLLERRTVLQLLLGNPNKGKSEKKEKTPLRDESTQEHSERALSEQI
LMVKIKSEPCDDLQIPNTNVHLSHDAKSAPFLGMAPAVQRSAPALPVSED
FKSEPVSPQDFSFSKNGLLSRLLRQNQDSYLADDSDRSHRNNEMALLESK
NLCMVPKKRKLYTEPLENPFKKMKNNIVDAANNHSAPEVLYGSLLNQEEL
KFSRNDLEFKYPAGHGSASESEHRSWARESKSFNVLKQLLLSENCVRDLS
PHRSNSVADSKKKGHKNNVTNSKPEFSISSLNGLMYSSTQPSSCMDNRTF
SYPGVVKTPVSPTFPEHLGCAGSRPESGLLNGCSMPSEKGPIKWVITDAE
KNEYEKDSPRLTKTNPILYYMLQKGGNSVTSRETQDKDIWREASSAESVS
QVTAKEELLPTAETKASFFNLRSPYNSHMGNNASRPHSANGEVYGLLGSV
LTIKKESE

Funkcija

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Protein 1 koji interaguje s jedarnim receptorom (NRIP1) je jedarni protein koji specifično stupa u interakciju sa hormonski ovisnim aktivacijskim domenom AF2 jedarnih receptora. Također poznat kao RIP140, ovaj protein je ključni regulator koji modulira transkripcijsku aktivnost raznih transkripcionih faktora, uključujući estrogeni receptor.[7]

RIP140 ima važnu ulogu u regulaciji metabolizma lipida i glukoze,[8] i reguliše ekspresije gena u metaboličkim tkivima uključujući srčano,[9] skeletal muscle,[10] i jetreno .[11] Glavna uloga RIP140 u masnom tkivu je da blokira ekspresiju gena uključenih u disipaciju energije i odvajanje mitohondrija, uključujući razdvajanje proteina 1 i karnitin palmitoiltransferazu 1b.[12]

Estrogen-srodni receptor alfa (ERRa) može aktivirati RIP140 tokom adipogeneze, putem direktnog vezivanja za element estrogenog receptora /ERR elementa i indirektno preko Sp1 vezivanja za proksimalni promotivni dio.[13]

RIP140 potiskuje ekspresiju mitohondrijskih proteina sukcinat-dehidrogenaza kompleksa b i CoxVb i djeluje kao negativni regulator uzimanja glukoze kod miševa.[14]

Studije nokauta

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Nokaut-miševi kojima potpuno nedostaje molekula RIP140 su vitki i ostaju vitki, čak i na bogatoj ishrani.[15]

Ženke nokaut.miševe također su neplodne jer ne uspijevaju ovulirati.[16] Neuspjeh ovulacije kod ovih miševa uzrokovan je nedostatkom ekspanzije cumulus i promijenjenom ekspresijom različitih gena, uključujući amfiregulin, u jajničkim folikulima.[17][18]

Klinički značaj

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RIP140 je dio lanca kojim tumori mogu uzrokovati kaheksiju.[19][20]

Nivoi ekspresije RIP140 u različitim tkivima variraju tokom starenja kod miševa, što ukazuje na promjene u metaboličkoj funkciji.[21] RIP140 je uključen u određene procese bolesti kod ljudi. Kod morbidne gojaznosti, nivoi RIP140 su smanjeni u visceralnom masnom tkivu.[22] Kod raka dojke, RIP140 je uključen u regulaciju E2F1, onkogena koji diferencira lumenske i bazne tipove tumora. RIP140 ima uticaj na fenotip i prognozu raka.[23] Osim toga, RIP140 ima ulogu u upalama, jer djeluje kao koaktivator za NFkappaB/RelA zavisnu citokinsku ekspresiju gena. Nedostatak RIP140 dovodi do inhibicije proupalnih puteva u makrofaga.[24]

Interakcije

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Pokazalo se da je NRIP1 u interakciji sa:

Također pogledajte

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Referenc

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000180530 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048490 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Cavailles V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG (Sep 1995). "Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor". EMBO J. 14 (15): 3741–51. doi:10.1002/j.1460-2075.1995.tb00044.x. PMC 394449. PMID 7641693.
  6. ^ Katsanis N, Ives JH, Groet J, Nizetic D, Fisher EM (Apr 1998). "Localisation of receptor interacting protein 140 (RIP140) within 100 kb of D21S13 on 21q11, a gene-poor region of the human genome". Hum Genet. 102 (2): 221–3. doi:10.1007/s004390050682. PMID 9521594. S2CID 1042332.
  7. ^ a b "Entrez Gene: NRIP1 nuclear receptor interacting protein 1".
  8. ^ Rosell M, Jones MC, Parker MG (2010). "Role of nuclear receptor corepressor RIP140 in metabolic syndrome". Biochim Biophys Acta. 1812 (8): 919–28. doi:10.1016/j.bbadis.2010.12.016. PMC 3117993. PMID 21193034.
  9. ^ Fritah A, Steel JH, Nichol D, Parker N, Williams S, Price A, Strauss L, Ryder TA, Mobberley MA, Poutanen M, Parker M, White R (2010). "Elevated expression of the metabolic regulator receptor-interacting protein 140 results in cardiac hypertrophy and impaired cardiac function". Cardiovasc Res. 86 (3): 443–451. doi:10.1093/cvr/cvp418. PMC 2868176. PMID 20083575.
  10. ^ 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 (Sep 2007). "The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle". Cell Metab. 6 (3): 236–245. doi:10.1016/j.cmet.2007.08.004. PMC 2680991. PMID 17767910.
  11. ^ Herzog B, Hallberg M, Seth A, Woods A, White R, Parker MG (Nov 2007). "The nuclear receptor cofactor, receptor-interacting protein 140, is required for the regulation of hepatic lipid and glucose metabolism by liver X receptor". Mol Endocrinol. 21 (11): 2687–97. doi:10.1210/ME.2007-0213. PMC 2140279. PMID 17684114.
  12. ^ Debevec D, Christian M, Morganstein D, Seth A, Herzog B, Parker M, White R (July 2007). "Receptor interacting protein 140 regulates expression of uncoupling protein 1 in adipocytes through specific peroxisome proliferator activated receptor isoforms and estrogen-related receptor alpha". Mol. Endocrinol. 21 (7): 1581–92. doi:10.1210/me.2007-0103. PMC 2072047. PMID 17456798.
  13. ^ Nichol D, Christian M, Steel JH, White R, Parker MG (Oct 2006). "RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis". J Biol Chem. 281 (43): 32140–32147. doi:10.1074/jbc.M604803200. PMID 16923809.
  14. ^ Powelka AM, Seth A, Virbasius JV, Kiskinis E, Nicoloro SM, Guilherme A, Tang X, Straubhaar J, Cherniack AD, Parker MG, Czech MP (2006). "Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes". J Clin Invest. 116 (1): 125–136. doi:10.1172/JCI26040. PMC 1319222. PMID 16374519.
  15. ^ Leonardsson G, Steel JH, Christian M, Pocock V, Milligan S, Bell J, So PW, Medina-Gomez G, Vidal-Puig A, White R, Parker MG (May 2004). "Nuclear receptor corepressor RIP140 regulates fat accumulation". Proc Natl Acad Sci U S A. 101 (22): 8437–42. Bibcode:2004PNAS..101.8437L. doi:10.1073/pnas.0401013101. PMC 420412. PMID 15155905.
  16. ^ White R, Leonardsson G, Rosewell I, Ann Jacobs M, Milligan S, Parker M (Dec 2000). "The nuclear receptor co-repressor nrip1 (RIP140) is essential for female fertility". Nat. Med. 6 (12): 1368–74. doi:10.1038/82183. PMID 11100122. S2CID 20285964.
  17. ^ Tullet JM, Pocock V, Steel JH, White R, Milligan S, Parker MG (2005). "Multiple Signaling Defects in the Absence of RIP140 Impair Both Cumulus Expansion and Follicle Rupture". Endocrinology. 146 (9): 4127–4137. doi:10.1210/EN.2005-0348. PMID 15919748.
  18. ^ Nautiyal J, Steel JH, Rosell MM, Nikolopoulou E, Lee K, Demayo FJ, White R, Richards JS, Parker MG (2010). "The nuclear receptor cofactor receptor-interacting protein 140 is a positive regulator of amphiregulin expression and cumulus cell-oocyte complex expansion in the mouse ovary". Endocrinology. 151 (6): 2923–2932. doi:10.1210/EN.2010-0081. PMC 2875814. PMID 20308529.
  19. ^ "A common denominator of inflammations and fatty liver". News. Science Centric. 2008-05-31. Pristupljeno 2008-08-31. [mrtav link]
  20. ^ Diaz MB, Krones-Herzig A, Metzger D, Ziegler A, Vegiopoulos A, Klingenspor M, Müller-Decker K, Herzig S (April 2008). "Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice". Hepatology. 48 (3): 782–791. doi:10.1002/hep.22383. PMID 18712775. S2CID 26235707.
  21. ^ Ghosh S, Thakur MK (2008). "Tissue-specific expression of receptor-interacting protein in aging mouse". Age (Dordr). 30 (4): 237–243. doi:10.1007/s11357-008-9062-3. PMC 2585652. PMID 19424847.
  22. ^ Catalán V, Gómez-Ambrosi J, Lizanzu A, Rodríguez A, Silva C, Rotellar F, Gil MJ, Cienfuegos JA, Salvador J, Frühbeck G (2009). "RIP140 gene and protein expression levels are downregulated in visceral adipose tissue in human morbid obesity". Obes Surg. 19 (6): 771–776. doi:10.1007/s11695-009-9834-6. PMID 19367438. S2CID 787869.
  23. ^ Docquier A, Harmand PO, Fritsch S, Chanrion M, Darbon JM, Cavaillès V (2010). "The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes". Clin Cancer Res. 16 (11): 2959–2970. doi:10.1158/1078-0432.CCR-09-3153. PMC 3112174. PMID 20410059.
  24. ^ Zschiedrich I, Hardeland U, Krones-Herzig A, Berriel DM, Vegiopoulos A, Müggenburg J, Sombroek D, Hofmann TG, Zawatzky R, Yu X, Gretz N, Christian M, White R, Parker MG, Herzig S (2008). "Coactivator function of RIP140 for NFkappaB/RelA-dependent cytokine gene expression". Blood. 112 (2): 264–276. doi:10.1182/blood-2007-11-121699. PMID 18469200.
  25. ^ Kumar MB, Tarpey RW, Perdew GH (Aug 1999). "Differential recruitment of coactivator RIP140 by Ah and estrogen receptors. Absence of a role for LXXLL motifs". J. Biol. Chem. 274 (32): 22155–64. doi:10.1074/jbc.274.32.22155. PMID 10428779.
  26. ^ a b c Castet A; Boulahtouf Abdelhay; Versini Gwennaëlle; Bonnet Sandrine; Augereau Patrick; Vignon Françoise; Khochbin Saadi; Jalaguier Stéphan; Cavaillès Vincent (2004). "Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition". Nucleic Acids Res. 32 (6): 1957–66. doi:10.1093/nar/gkh524. PMC 390375. PMID 15060175.
  27. ^ Perissi V; Scafoglio Claudio; Zhang Jie; Ohgi Kenneth A; Rose David W; Glass Christopher K; Rosenfeld Michael G (Mar 2008). "TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints". Mol. Cell. 29 (6): 755–66. doi:10.1016/j.molcel.2008.01.020. PMC 2364611. PMID 18374649.
  28. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  29. ^ a b Sugawara T, Abe S, Sakuragi N, Fujimoto Y, Nomura E, Fujieda K, Saito M, Fujimoto S (August 2001). "RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1". Endocrinology. 142 (8): 3570–7. doi:10.1210/en.142.8.3570. PMID 11459805.
  30. ^ Hu X; Chen Yixin; Farooqui Mariya; Thomas Mary C; Chiang Cheng-Ming; Wei Li-Na (Jan 2004). "Suppressive effect of receptor-interacting protein 140 on coregulator binding to retinoic acid receptor complexes, histone-modifying enzyme activity, and gene activation". J. Biol. Chem. 279 (1): 319–25. doi:10.1074/jbc.M307621200. PMID 14581481.
  31. ^ a b Farooqui M; Franco Peter J; Thompson Jim; Kagechika Hiroyuki; Chandraratna Roshantha A S; Banaszak Len; Wei Li-Na (Feb 2003). "Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity". Biochemistry. 42 (4): 971–9. doi:10.1021/bi020497k. PMID 12549917.
  32. ^ a b c L'Horset F, Dauvois S, Heery DM, Cavaillès V, Parker MG (Nov 1996). "RIP-140 interacts with multiple nuclear receptors by means of two distinct sites". Mol. Cell. Biol. 16 (11): 6029–36. doi:10.1128/MCB.16.11.6029. PMC 231605. PMID 8887632.
  33. ^ Thénot S, Henriquet C, Rochefort H, Cavaillès V (May 1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". J. Biol. Chem. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.
  34. ^ a b Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (Apr 2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. 15 (4): 501–11. doi:10.1210/mend.15.4.0624. PMID 11266503.
  35. ^ Tazawa H; Osman Waffa; Shoji Yutaka; Treuter Eckardt; Gustafsson Jan-Ake; Zilliacus Johanna (Jun 2003). "Regulation of subnuclear localization is associated with a mechanism for nuclear receptor corepression by RIP140". Mol. Cell. Biol. 23 (12): 4187–98. doi:10.1128/MCB.23.12.4187-4198.2003. PMC 156128. PMID 12773562.
  36. ^ Subramaniam N, Treuter E, Okret S (Jun 1999). "Receptor interacting protein RIP140 inhibits both positive and negative gene regulation by glucocorticoids". J. Biol. Chem. 274 (25): 18121–7. doi:10.1074/jbc.274.25.18121. PMID 10364267.
  37. ^ Mellgren G; Børud Bente; Hoang Tuyen; Yri Olav Erich; Fladeby Cathrine; Lien Ernst Asbjørn; Lund Johan (May 2003). "Characterization of receptor-interacting protein RIP140 in the regulation of SF-1 responsive target genes". Mol. Cell. Endocrinol. 203 (1–2): 91–103. doi:10.1016/S0303-7207(03)00097-2. PMID 12782406. S2CID 733221.

Dopunska literatura

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Vanjski linkovi

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Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

Šablon:Transcripcijsku koregulatori

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