PIAS3

PIAS3
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4MVT
Identifikatori
Aliasi	PIAS3
Vanjski ID-jevi	OMIM: 605987 MGI: 1913126 HomoloGene: 4447 GeneCards: PIAS3
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	145,859,836 bp
Lokacija gena (miš)
Hrom.	Hromosom 3 (miš)
Kraj	96,613,386 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• protein N-terminus binding; • vezivanje iona cinka; • vezivanje iona metala; • potassium channel regulator activity; • protein C-terminus binding; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje enzima; • SUMO transferase activity; • aktivnost sa transferazom;
Ćelijska komponenta	• citoplazma; • nuclear speck; • sinapsa; • nukleoplazma; • dendrit; • jedro;
Biološki proces	• negative regulation of protein sumoylation; • GO:0009373 regulation of transcription, DNA-templated; • positive regulation of protein sumoylation; • protein sumoylation; • transcription, DNA-templated; • GO:1901313 positive regulation of gene expression; • response to hormone; • positive regulation of membrane potential; • GO:1901227 negative regulation of transcription by RNA polymerase II; • negative regulation of gene expression; • negative regulation of osteoclast differentiation; • GO:0045996 negative regulation of transcription, DNA-templated; • TNFSF11-mediated signaling pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	10401
	229615
	ENSG00000131788
	ENSMUSG00000028101
	Q9Y6X2
	O54714
	NM_006099
	NM_001165949; NM_018812; NM_146135
	NP_006090
	NP_001159421; NP_061282; NP_666247
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

E3 SUMO-protein-ligaza PIAS3 jest enzim koji je kod ljudi kodiran genom PIAS3 sa hromosoma 1.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 628 aminokiselina, a molekulska težina 68.017 Da.^[7]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MAELGELKHM	VMSFRVSELQ	VLLGFAGRNK	SGRKHELLAK	ALHLLKSSCA
PSVQMKIKEL	YRRRFPRKTL	GPSDLSLLSL	PPGTSPVGSP	GPLAPIPPTL
LAPGTLLGPK	REVDMHPPLP	QPVHPDVTMK	PLPFYEVYGE	LIRPTTLAST
SSQRFEEAHF	TFALTPQQVQ	QILTSREVLP	GAKCDYTIQV	QLRFCLCETS
CPQEDYFPPN	LFVKVNGKLC	PLPGYLPPTK	NGAEPKRPSR	PINITPLARL
SATVPNTIVV	NWSSEFGRNY	SLSVYLVRQL	TAGTLLQKLR	AKGIRNPDHS
RALIKEKLTA	DPDSEVATTS	LRVSLMCPLG	KMRLTVPCRA	LTCAHLQSFD
AALYLQMNEK	KPTWTCPVCD	KKAPYESLII	DGLFMEILSS	CSDCDEIQFM
EDGSWCPMKP	KKEASEVCPP	PGYGLDGLQY	SPVQGGDPSE	NKKKVEVIDL
TIESSSDEED	LPPTKKHCSV	TSAAIPALPG	SKGVLTSGHQ	PSSVLRSPAM
GTLGGDFLSS	LPLHEYPPAF	PLGADIQGLD	LFSFLQTESQ	HYGPSVITSL
DEQDALGHFF	QYRGTPSHFL	GPLAPTLGSS	HCSATPAPPP	GRVSSIVAPG
GALREGHGGP	LPSGPSLTGC	RSDIISLD

Funkcija

PIAS3 protein također funkcionira kao SUMO (mali modifikator sličan ubikvitinu)-E3 ligaza, koja katalizira kovalentno vezivanje SUMO proteina na specifične ciljne supstrate. Direktno se vezuje za nekoliko faktora transkripcije i ili blokira ili pojačava njihovu aktivnost. Identificirane su alternativno prerađene varijante transkripta ovog gena su ali priroda nekih od ovih varijanti u punoj dužini nije utvrđena.^[6]

Porodica PIAS

Sisarska porodica PIAS ima četiri člana: PIAS1, PIAS2, PIAS3 i PIAS4. U rodu Drosophila identificiran je jedan homolog PIAS-a pod nazivom dPIAS/Zimp.^[8] In yeast, two PIAS-related proteins were identified namely SIZ1 and SIZ2.^[9] Porodica PIAS sadrži više od 60 proteina, od kojih su većina transkripcijski faktori koji se mogu pozitivno ili negativno regulirati putem više mehanizama.

Domeni

SAF-A/B, Acinus i PIAS (SAP) domen nalaze se na N-terminalu PIAS proteina.^[10] Ovaj evolucijski konzervirani domen nalazi se u proteinima u rasponu od kvasca do ljudi i dijele ga drugi proteini koji vežu hromatin, kao što su faktor vezivanja skela A i B.^[11] Domen SAP prepotznaje i veže AT-bogate sekvence DNK DNA i rigijama dodataka skele i matriksa.^[12] Ovi elementi se često nalaze u blizini pojačivača gena i stupaju u interakciju s proteinima jearnog matriksa, kako bi osigurali jedinstveno jedarno mikrookruženje za regulaciju transkripcije. LXXLL potpisni motiv prisutan je u SAP domenu svih PIAS proteina. Pokazalo se da ovaj prepoznatljivi motiv posreduje u interakcijama između jedarnih receptora i njihovih koregulatora.^[13] Također je neophodan za vezivanje PIAS3 za androgeni receptor. Motiv LXXLL predstavlja minimalni zahtjev za interakciju sa NFκB p65 podjedinicom i za inhibiciju transkripcijske aktivnosti NFκB. Motiv LXXLL također je odgovoran za zadržavanje PIAS3 u jedru.

Pro-Ile-Asn-Ile-Thr (PINIT) motiv predstavlja visoko konzerviranu regiju PIAS proteina, za koju se pokazalo da je uključena u jedarno zadržavanje PIAS3.^[14] Unutar PINIT domena, regija PIAS382-132 izolirana je i okarakterizirana kao inhibitorni domen koji veže i inhibira i transktipcijske faktore MITF i STAT3.^[15] RING-prstoliku cink-vezujući domen je jedan od najkonzerviranijih domena porodice PIAS i pokazalo se da je važan za aktivnost PIAS3 kao SUMO-E3 ligaza.^[16] The RLD domain is also involved in the positive regulation of SMAD3 by PIAS3.^[17]

Interakcije

Pokazalo se da PIAS3 ima interakcije sa:

Srodni genski problemi

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000131788 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028101 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Ueki N, Seki N, Yano K, Saito T, Masuho Y, Muramatsu M (juni 1999). "Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3)". Journal of Human Genetics. 44 (3): 193–6. doi:10.1007/s100380050141. PMID 10319586. S2CID 12454718.
^ ^a ^b "Entrez Gene: PIAS3 protein inhibitor of activated STAT, 3".
^ "UniProt, Q9Y6X2" (jezik: engleski). Pristupljeno 16. 12. 2021.
^ Mohr SE, Boswell RE (Mar 1999). "Zimp encodes a homologue of mouse Miz1 and PIAS3 and is an essential gene in Drosophila melanogaster". Gene. 229 (1–2): 109–16. doi:10.1016/s0378-1119(99)00033-5. PMID 10095110.
^ Islam HK, Fujioka Y, Tomidokoro T, Sugiura H, Takahashi T, Kondo S, Katoh H (2001). "Immunohistochemical study of genetic alterations in intraductal and invasive ductal tumors of the pancreas". Hepato-Gastroenterology. 48 (39): 879–83. PMID 11462947.
^ Shuai K (Feb 2006). "Regulation of cytokine signaling pathways by PIAS proteins". Cell Research. 16 (2): 196–202. doi:10.1038/sj.cr.7310027. PMID 16474434. S2CID 755228.
^ Aravind L, Koonin EV (2000). "SAP - a putative DNA-binding motif involved in chromosomal organization". Trends in Biochemical Sciences. 25 (3): 112–4. doi:10.1016/s0968-0004(99)01537-6. PMID 10694879.
^ Kipp, M.; et al. (2000). "SAF-Box, a conserved protein domain that specifically recognizes scaffold attachment region DNA". Mol Cell Biol. 20 (20): 7480–7489. doi:10.1128/mcb.20.20.7480-7489.2000. PMC 86301. PMID 11003645.
^ Glass CK, Rosenfeld MG (Jan 2000). "The coregulator exchange in transcriptional functions of nuclear receptors". Genes & Development. 14 (2): 121–41. doi:10.1101/gad.14.2.121 (neaktivno 31. 10. 2021). PMID 10652267.CS1 održavanje: DOI nije aktivan od 2021 (link)
^ Duval D, Duval G, Kedinger C, Poch O, Boeuf H (Nov 2003). "The 'PINIT' motif, of a newly identified conserved domain of the PIAS protein family, is essential for nuclear retention of PIAS3L". FEBS Letters. 554 (1–2): 111–8. doi:10.1016/s0014-5793(03)01116-5. PMID 14596924. S2CID 23261716.
^ Levy C, Khaled M, Fisher DE (Sep 2006). "MITF: master regulator of melanocyte development and melanoma oncogene". Trends in Molecular Medicine. 12 (9): 406–14. doi:10.1016/j.molmed.2006.07.008. PMID 16899407.
^ Nakagawa, K.; Yokosawa, H. (2002). "PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1". FEBS Lett. 530 (1–3): 204–208. doi:10.1016/s0014-5793(02)03486-5. PMID 12387893. S2CID 38456991.
^ Long J, Wang G, Matsuura I, He D, Liu F (Jan 2004). "Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3)". Proceedings of the National Academy of Sciences of the United States of America. 101 (1): 99–104. Bibcode:2004PNAS..101...99L. doi:10.1073/pnas.0307598100. PMC 314145. PMID 14691252.
^ Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, Heinrich P, Shuai K, Elsässer HP, Möröy T (Nov 2000). "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". EMBO J. 19 (21): 5845–55. doi:10.1093/emboj/19.21.5845. PMC 305799. PMID 11060035.
^ Zentner MD, Lin HH, Deng HT, Kim KJ, Shih HM, Ann DK (Aug 2001). "Requirement for high mobility group protein HMGI-C interaction with STAT3 inhibitor PIAS3 in repression of alpha-subunit of epithelial Na+ channel (alpha-ENaC) transcription by Ras activation in salivary epithelial cells". J. Biol. Chem. 276 (32): 29805–14. doi:10.1074/jbc.M103153200. PMID 11390395. S2CID 33084417.
^ Yagil Z, Nechushtan H, Kay G, Yang CM, Kemeny DM, Razin E (maj 2010). "The enigma of the role of protein inhibitor of activated STAT3 (PIAS3) in the immune response". Trends Immunol. 31 (5): 199–204. doi:10.1016/j.it.2010.01.005. PMID 20181527.
^ ^a ^b Long J, Wang G, Matsuura I, He D, Liu F (Jan 2004). "Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3)". Proc. Natl. Acad. Sci. U.S.A. 101 (1): 99–104. Bibcode:2004PNAS..101...99L. doi:10.1073/pnas.0307598100. PMC 314145. PMID 14691252.
^ Klopocki E, Schulze H, Strauss G, Ott CE, Hall J, Trotier F, Fleischhauer S, Greenhalgh L, Newbury-Ecob RA, Neumann LM, Habenicht R, König R, Seemanova E, Megarbane A, Ropers HH, Ullmann R, Horn D, Mundlos S (Feb 2007). "Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome". American Journal of Human Genetics. 80 (2): 232–40. doi:10.1086/510919. PMC 1785342. PMID 17236129.

Dopunska literatura

Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K (Dec 1997). "Specific inhibition of Stat3 signal transduction by PIAS3". Science. 278 (5344): 1803–5. Bibcode:1997Sci...278.1803C. doi:10.1126/science.278.5344.1803. PMID 9388184.
Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, Heinrich P, Shuai K, Elsässer HP, Möröy T (Nov 2000). "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". The EMBO Journal. 19 (21): 5845–55. doi:10.1093/emboj/19.21.5845. PMC 305799. PMID 11060035.
Junicho A, Matsuda T, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A (Nov 2000). "Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells". Biochemical and Biophysical Research Communications. 278 (1): 9–13. doi:10.1006/bbrc.2000.3753. PMID 11071847.
Kotaja N, Aittomäki S, Silvennoinen O, Palvimo JJ, Jänne OA (Dec 2000). "ARIP3 (androgen receptor-interacting protein 3) and other PIAS (protein inhibitor of activated STAT) proteins differ in their ability to modulate steroid receptor-dependent transcriptional activation". Molecular Endocrinology. 14 (12): 1986–2000. doi:10.1210/mend.14.12.0569. PMID 11117529.
Zentner MD, Lin HH, Deng HT, Kim KJ, Shih HM, Ann DK (Aug 2001). "Requirement for high mobility group protein HMGI-C interaction with STAT3 inhibitor PIAS3 in repression of alpha-subunit of epithelial Na+ channel (alpha-ENaC) transcription by Ras activation in salivary epithelial cells". The Journal of Biological Chemistry. 276 (32): 29805–14. doi:10.1074/jbc.M103153200. PMID 11390395. S2CID 33084417.
Wang LH, Yang XY, Mihalic K, Xiao W, Li D, Farrar WL (Aug 2001). "Activation of estrogen receptor blocks interleukin-6-inducible cell growth of human multiple myeloma involving molecular cross-talk between estrogen receptor and STAT3 mediated by co-regulator PIAS3". The Journal of Biological Chemistry. 276 (34): 31839–44. doi:10.1074/jbc.M105185200. PMID 11429412. S2CID 24912586.
Jiménez-Lara AM, Heine MJ, Gronemeyer H (Aug 2002). "PIAS3 (protein inhibitor of activated STAT-3) modulates the transcriptional activation mediated by the nuclear receptor coactivator TIF2". FEBS Letters. 526 (1–3): 142–6. doi:10.1016/S0014-5793(02)03154-X. PMID 12208521. S2CID 2934712.
Nakagawa K, Yokosawa H (Oct 2002). "PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1". FEBS Letters. 530 (1–3): 204–8. doi:10.1016/S0014-5793(02)03486-5. PMID 12387893. S2CID 38456991.
Yamamoto T, Sato N, Sekine Y, Yumioka T, Imoto S, Junicho A, Fuse H, Matsuda T (Jun 2003). "Molecular interactions between STAT3 and protein inhibitor of activated STAT3, and androgen receptor". Biochemical and Biophysical Research Communications. 306 (2): 610–5. doi:10.1016/S0006-291X(03)01026-X. hdl:2115/28119. PMID 12804609.
Di Y, Li J, Zhang Y, He X, Lu H, Xu D, Ling J, Huo K, Wan D, Li YY, Gu J (Jun 2003). "HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins". Journal of Biochemistry. 133 (6): 713–8. doi:10.1093/jb/mvg091. PMID 12869526.
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Long J, Wang G, Matsuura I, He D, Liu F (Jan 2004). "Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3)". Proceedings of the National Academy of Sciences of the United States of America. 101 (1): 99–104. Bibcode:2004PNAS..101...99L. doi:10.1073/pnas.0307598100. PMC 314145. PMID 14691252.
Nojiri S, Joh T, Miura Y, Sakata N, Nomura T, Nakao H, Sobue S, Ohara H, Asai K, Ito M (Jan 2004). "ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3". Biochemical and Biophysical Research Communications. 314 (1): 97–103. doi:10.1016/j.bbrc.2003.12.054. PMID 14715251.
Wang L, Banerjee S (Jun 2004). "Differential PIAS3 expression in human malignancy". Oncology Reports. 11 (6): 1319–24. doi:10.3892/or.11.6.1319. PMID 15138572.
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