PIAS3

PIAS3
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

4MVT

Identifikatori
AliasiPIAS3
Vanjski ID-jeviOMIM: 605987 MGI: 1913126 HomoloGene: 4447 GeneCards: PIAS3
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za PIAS3
Genomska lokacija za PIAS3
Bend1q21.1Početak145,848,522 bp[1]
Kraj145,859,836 bp[1]
Lokacija gena (miš)
Hromosom 3 (miš)
Hrom.Hromosom 3 (miš)[2]
Hromosom 3 (miš)
Genomska lokacija za PIAS3
Genomska lokacija za PIAS3
Bend3|3 F2.1Početak96,603,700 bp[2]
Kraj96,613,386 bp[2]
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
VrsteČovjekMiš
Entrez

10401

229615

Ensembl

ENSG00000131788

ENSMUSG00000028101

UniProt

Q9Y6X2

O54714

RefSeq (mRNK)

NM_006099

NM_001165949
NM_018812
NM_146135

RefSeq (bjelančevina)

NP_006090

NP_001159421
NP_061282
NP_666247

Lokacija (UCSC)Chr 1: 145.85 – 145.86 MbChr 3: 96.6 – 96.61 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/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]

1020304050
MAELGELKHMVMSFRVSELQVLLGFAGRNKSGRKHELLAKALHLLKSSCA
PSVQMKIKELYRRRFPRKTLGPSDLSLLSLPPGTSPVGSPGPLAPIPPTL
LAPGTLLGPKREVDMHPPLPQPVHPDVTMKPLPFYEVYGELIRPTTLAST
SSQRFEEAHFTFALTPQQVQQILTSREVLPGAKCDYTIQVQLRFCLCETS
CPQEDYFPPNLFVKVNGKLCPLPGYLPPTKNGAEPKRPSRPINITPLARL
SATVPNTIVVNWSSEFGRNYSLSVYLVRQLTAGTLLQKLRAKGIRNPDHS
RALIKEKLTADPDSEVATTSLRVSLMCPLGKMRLTVPCRALTCAHLQSFD
AALYLQMNEKKPTWTCPVCDKKAPYESLIIDGLFMEILSSCSDCDEIQFM
EDGSWCPMKPKKEASEVCPPPGYGLDGLQYSPVQGGDPSENKKKVEVIDL
TIESSSDEEDLPPTKKHCSVTSAAIPALPGSKGVLTSGHQPSSVLRSPAM
GTLGGDFLSSLPLHEYPPAFPLGADIQGLDLFSFLQTESQHYGPSVITSL
DEQDALGHFFQYRGTPSHFLGPLAPTLGSSHCSATPAPPPGRVSSIVAPG
GALREGHGGPLPSGPSLTGCRSDIISLD

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131788 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028101 - 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. ^ 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.
  6. ^ a b "Entrez Gene: PIAS3 protein inhibitor of activated STAT, 3".
  7. ^ "UniProt, Q9Y6X2" (jezik: engleski). Pristupljeno 16. 12. 2021.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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)
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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

Vanjski linkovi

Šablon:Signalni put JAK-STAT

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