PIAS3

PIAS3
사용 가능한 구조물
PDB	직교 검색: PDBe RCSB
PDB ID 코드 목록
	4MVT
식별자
별칭	PIAS3, ZMIZ5, 활성화된 STAT 3의 단백질 억제제
외부 ID	OMIM: 605987 MGI: 1913126 호몰로Gene: 4447 GeneCard: PIAS3
유전자 위치(인간)
쳇.	염색체 1 (인간)
끝	145,859,836 bp
유전자 위치(마우스)
쳇.	3번 염색체(쥐)
끝	96,613,192 bp
RNA 표현 패턴
	표현된 상단
	흉부 대동맥; ; 식도; ; 오른쪽 관상동맥; ; 질질 끌다;
	추가 참조 표현식 데이터
	추가 참조 표현식 데이터
유전자 온톨로지
분자함수	단백질 N단자 결합; 아연 이온 결합; 금속 이온 결합; 칼륨 채널 조절기 활성; 단백질 C-단자 결합; GO:0001948 단백질 결합; 효소 결합; SMO 전이효소 활동; 전이효소 활동;
셀룰러 컴포넌트	세포질; 핵 반점; 시냅스; 핵종의; 덴드라이트; 핵의;
생물학적 과정	단백질 분비에 대한 부정적인 규제; 전사 규정, DNA-템플링; 단백질 분비에 대한 양성 조절; 단백질 수포화; 전사, DNA-템플릿; 유전자 발현에 대한 양성 규제; 호르몬에 대한 반응; 막 전위의 양성 조절; RNA 중합효소 II에 의한 전사의 음성 조절; 유전자 발현에 대한 부정적인 규제; 골성 분화의 부정적 규제; 전사의 음성적 조절, DNA-템플링; TNFSF11 매개 신호 경로;
	출처:아미고 / 퀵고
직교체
	10401
	229615
	ENSG00000131788
	ENSMUSG00000028101
	Q9Y6X2
	O54714
	NM_006099
	NM_001165949; NM_018812; NM_146135
	NP_006090
	NP_001159421; NP_061282; NP_666247
	위키다타
인간 보기/편집	마우스 보기/편집

E3 스모-단백질 리기아제 PIAS3는 인간에게 PIAS3 유전자에 의해 암호화된 효소다.^[5]^[6]

PIAS 가족

포유류 PIAS 제품군은 PIAS1, PIAS2, PIAS3, PIAS4의 4개 구성원으로 구성된다.드로소필라에서는 dPIAS/Zimp라는 단일 PIAS 호몰로뉴가 확인되었다.^[7]효모에서는 두 개의 PIAS 관련 단백질인 SIZ1과 SIZ2가 확인되었다.^[8]PIAS 계열은 60개 이상의 단백질을 포함하고 있으며, 대부분은 다중 메커니즘을 통해 긍정적이거나 부정적으로 조절될 수 있는 전사 인자를 포함하고 있다.

디스커버리

IAS 단백질은 원래 Janus Kinase (JAK)/STAT 신호 경로를 해독하기 위한 연구에서 확인되었다.원래 PIAS3는 인터루킨 -6 (IL-6) 활성 뮤린 골모래성 M1 세포에서 인산화 STAT3와 특별히 상호작용하는 것으로 밝혀졌다.^[9]이 상호작용은 PIAS3 바인딩을 통해 STAT3 DNA 바인딩 도메인에 매개된다.따라서 STAT3 전사 활동은 표적 유전자에 대한 결합의 물리적 예방에 의해 억제된다.그 후 PIAS3는 MITF,^[10] NFκB,^[11] SMAD^[12], 에스트로겐 수용체 등 다른 주요 전사 인자의 조절 단백질로도 밝혀졌다.^[13]

함수

PIAS3 단백질은 또한 특정 대상 기질에 대한 SMO 단백질의 공동 부착을 촉진하는 SMO(Small ubiquitin-ligase)-E3 리게아제 역할도 한다.그것은 직접적으로 몇몇 전사 요인에 결합하고 그들의 활동을 차단하거나 강화시킨다.대안으로 이 유전자의 분할된 대본 변형은 확인되었지만, 이러한 변종들 중 일부의 전체적 특성은 결정되지 않았다.^[6]

도메인

SAF-A/B, Acinus 및 PIAS(SAP) 영역은 PIAS 단백질의 N단자에 위치한다.^[14]이 진화적으로 보존된 영역은 효모에서 인간에 이르는 단백질에서 발견되며 비계 부착 인자 A와 B와 같은 다른 염색체 결합 단백질에 의해 공유된다.^[15]SAP 도메인은 비계 부착 영역/매트릭스 부착 영역에 존재하는 AT가 풍부한 DNA 시퀀스를 인식하고 바인딩할 수 있다.^[16]이러한 원소들은 유전자 증식기 근처에서 자주 발견되며 전사를 위한 독특한 핵 미세 환경을 제공하기 위해 핵 매트릭스 단백질과 상호작용한다.모든 PIAS 단백질의 SAP 영역 내에 LXXLL 시그니처 모티브가 존재한다.이러한 시그니처 모티브는 핵수용체와 그 공동규제체 사이의 상호작용을 중재하는 것으로 나타났다.^[17]PIAS3와 안드로겐 수용체 결합에도 필수적이다.LXXLL 모티브는 NFκB p65 서브유닛과의 상호작용 및 NFbB 전사활동 억제에 대한 최소 요구사항을 나타낸다.^[11]앞서 LXXLL 모티브가 PIAS3를 핵에 유지하는 데에도 영향을 미친다고 기술했다.

PINIT(Pro-Ile-Asn-Ile-Thr) 모티브는 PIAS3의 핵 보유에 관여하는 것으로 보이는 PIAS 단백질의 보존도가 높은 영역을 나타낸다.^[18]PINIT 영역 내에서 PIAS382-132 영역은 격리되었고 MITF와 STAT3 전사 인자를 모두 결합하고 억제하는 억제 영역으로 특징지어졌다.^[19]RING-손가락 모양의 아연 결합 도메인(RLD)은 PIAS 제품군의 가장 보존된 도메인 중 하나이며, 스모-E3 리가제로서 PIAS3 활동에 중요한 것으로 나타났다.^[20]RLD 영역은 PIAS3에 의한 SMAD3의 양성 규제에도 관여한다.^[21]

상호작용

PIAS3는 다음과 상호 작용하는 것으로 나타났다.

참조

^ ^a ^b ^c GRCh38: 앙상블 릴리스 89: ENSG00000131788 - 앙상블, 2017년 5월
^ ^a ^b ^c GRCm38: 앙상블 릴리스 89: ENSMUSG000028101 - 앙상블, 2017년 5월
^ "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 (June 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".
^ 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.
^ 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.
^ ^a ^b Levy C, Nechushtan H, Razin E (Jan 2002). "A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor". The Journal of Biological Chemistry. 277 (3): 1962–6. doi:10.1074/jbc.m109236200. PMID 11709556. S2CID 25141003.
^ ^a ^b ^c Jang HD, Yoon K, Shin YJ, Kim J, Lee SY (Jun 2004). "PIAS3 suppresses NF-kappaB-mediated transcription by interacting with the p65/RelA subunit". The Journal of Biological Chemistry. 279 (23): 24873–80. doi:10.1074/jbc.m313018200. PMID 15140884. S2CID 20036187.
^ Bava KA, Gromiha MM, Uedaira H, Kitajima K, Sarai A (2004). "ProTherm, version 4.0: thermodynamic database for proteins and mutants". Nucleic Acids Research. 32 (Database issue): D120–1. doi:10.1093/nar/gkh082. PMC 308816. PMID 14681373.
^ Sentis S, Le Romancer M, Bianchin C, Rostan MC, Corbo L (2005). "Sumoylation of the estrogen receptor alpha hinge region regulates its transcriptional activity". Molecular Endocrinology (Baltimore, Md.). 19 (11): 2671–84. doi:10.1210/me.2005-0042. PMID 15961505.
^ 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. PMID 10652267. S2CID 12793980.
^ 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 (May 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.

추가 읽기

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.
Cheng J, Zhang D, Zhou C, Marasco WA (Jan 2004). "Down-regulation of SHP1 and up-regulation of negative regulators of JAK/STAT signaling in HTLV-1 transformed cell lines and freshly transformed human peripheral blood CD4+ T-cells". Leukemia Research. 28 (1): 71–82. doi:10.1016/S0145-2126(03)00158-9. PMID 14630083.
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.
Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (Jul 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.

외부 링크

PDB에서 UniProt: Q9Y6X2(E3 SIMO-단백질 리가제 PIAS3)에 사용할 수 있는 모든 구조 정보의 개요.

[refGRCh38Ensembl-1] GRCh38: 앙상블 릴리스 89: ENSG00000131788 - 앙상블, 2017년 5월

[refGRCm38Ensembl-2] GRCm38: 앙상블 릴리스 89: ENSMUSG000028101 - 앙상블, 2017년 5월

[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.

[pmid10319586-5] Ueki N, Seki N, Yano K, Saito T, Masuho Y, Muramatsu M (June 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.

[entrez-6] "Entrez Gene: PIAS3 protein inhibitor of activated STAT, 3".

[7] 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.

[8] 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.

[9] 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.

[Levy_2002-10] Levy C, Nechushtan H, Razin E (Jan 2002). "A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor". The Journal of Biological Chemistry. 277 (3): 1962–6. doi:10.1074/jbc.m109236200. PMID 11709556. S2CID 25141003.

[Jang_2004-11] Jang HD, Yoon K, Shin YJ, Kim J, Lee SY (Jun 2004). "PIAS3 suppresses NF-kappaB-mediated transcription by interacting with the p65/RelA subunit". The Journal of Biological Chemistry. 279 (23): 24873–80. doi:10.1074/jbc.m313018200. PMID 15140884. S2CID 20036187.

[pmid14681373-12] Bava KA, Gromiha MM, Uedaira H, Kitajima K, Sarai A (2004). "ProTherm, version 4.0: thermodynamic database for proteins and mutants". Nucleic Acids Research. 32 (Database issue): D120–1. doi:10.1093/nar/gkh082. PMC 308816. PMID 14681373.

[pmid15961505-13] Sentis S, Le Romancer M, Bianchin C, Rostan MC, Corbo L (2005). "Sumoylation of the estrogen receptor alpha hinge region regulates its transcriptional activity". Molecular Endocrinology (Baltimore, Md.). 19 (11): 2671–84. doi:10.1210/me.2005-0042. PMID 15961505.

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