PIAS4_HUMAN
ID PIAS4_HUMAN Reviewed; 510 AA.
AC Q8N2W9; O75926; Q96G19; Q9UN16;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=E3 SUMO-protein ligase PIAS4 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:12511558, ECO:0000269|PubMed:12631292, ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:15831457, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:32832608};
DE AltName: Full=PIASy {ECO:0000303|PubMed:11388671};
DE AltName: Full=Protein inhibitor of activated STAT protein 4;
DE AltName: Full=Protein inhibitor of activated STAT protein gamma;
DE Short=PIAS-gamma;
GN Name=PIAS4 {ECO:0000303|PubMed:32832608, ECO:0000312|HGNC:HGNC:17002};
GN Synonyms=PIASG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=B-cell;
RX PubMed=9724754; DOI=10.1073/pnas.95.18.10626;
RA Liu B., Liao J., Rao X., Kushner S.A., Chung C.D., Chang D.D., Shuai K.;
RT "Inhibition of Stat1-mediated gene activation by PIAS1.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:10626-10631(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Lung, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-510, FUNCTION, AND INTERACTION WITH TP53.
RX PubMed=11388671; DOI=10.1023/a:1011392811628;
RA Nelson V., Davis G.E., Maxwell S.A.;
RT "A putative protein inhibitor of activated STAT (PIASy) interacts with p53
RT and inhibits p53-mediated transactivation but not apoptosis.";
RL Apoptosis 6:221-234(2001).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH STAT1, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF 23-LEU-LEU-24.
RX PubMed=11248056; DOI=10.1073/pnas.051489598;
RA Liu B., Gross M., ten Hoeve J., Shuai K.;
RT "A transcriptional corepressor of Stat1 with an essential LXXLL signature
RT motif.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3203-3207(2001).
RN [5]
RP INTERACTION WITH AR, TISSUE SPECIFICITY, AND MUTAGENESIS OF 23-LEU-LEU-24.
RX PubMed=11439351; DOI=10.1038/sj.onc.1204489;
RA Gross M., Liu B., Tan J.-A., French F.S., Carey M., Shuai K.;
RT "Distinct effects of PIAS proteins on androgen-mediated gene activation in
RT prostate cancer cells.";
RL Oncogene 20:3880-3887(2001).
RN [6]
RP INTERACTION WITH AXIN1.
RX PubMed=12223491; DOI=10.1074/jbc.m208099200;
RA Rui H.L., Fan E., Zhou H.M., Xu Z., Zhang Y., Lin S.C.;
RT "SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK
RT activation but has no effect on Wnt signaling.";
RL J. Biol. Chem. 277:42981-42986(2002).
RN [7]
RP INTERACTION WITH GATA2.
RX PubMed=12750312; DOI=10.1161/01.res.0000076893.70898.36;
RA Chun T.-H., Itoh H., Subramanian L., Iniguez-Lluhi J.A., Nakao K.;
RT "Modification of GATA-2 transcriptional activity in endothelial cells by
RT the SUMO E3 ligase PIASy.";
RL Circ. Res. 92:1201-1208(2003).
RN [8]
RP FUNCTION IN SUMOYLATION OF TCF4, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-35; LYS-128; CYS-342 AND CYS-347.
RX PubMed=12727872; DOI=10.1093/emboj/cdg204;
RA Yamamoto H., Ihara M., Matsuura Y., Kikuchi A.;
RT "Sumoylation is involved in beta-catenin-dependent activation of Tcf-4.";
RL EMBO J. 22:2047-2059(2003).
RN [9]
RP FUNCTION IN SUMOYLATION OF MYB, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=12631292; DOI=10.1046/j.1432-1033.2003.03504.x;
RA Dahle O., Andersen T.O., Nordgaard O., Matre V., Del Sal G.,
RA Gabrielsen O.S.;
RT "Transactivation properties of c-Myb are critically dependent on two SUMO-1
RT acceptor sites that are conjugated in a PIASy enhanced manner.";
RL Eur. J. Biochem. 270:1338-1348(2003).
RN [10]
RP FUNCTION IN SUMOYLATION OF CEBPA, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=12511558; DOI=10.1074/jbc.m210440200;
RA Subramanian L., Benson M.D., Iniguez-Lluhi J.A.;
RT "A synergy control motif within the attenuator domain of CCAAT/enhancer-
RT binding protein alpha inhibits transcriptional synergy through its PIASy-
RT enhanced modification by SUMO-1 or SUMO-3.";
RL J. Biol. Chem. 278:9134-9141(2003).
RN [11]
RP INTERACTION WITH TICAM1.
RX PubMed=15251447; DOI=10.1016/j.febslet.2004.05.081;
RA Zhang J., Xu L.G., Han K.J., Wei X., Shu H.B.;
RT "PIASy represses TRIF-induced ISRE and NF-kappaB activation but not
RT apoptosis.";
RL FEBS Lett. 570:97-101(2004).
RN [12]
RP SUMOYLATION AT LYS-35 AND LYS-128, FUNCTION IN SUMOYLATION OF TCF4,
RP CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LYS-35 AND LYS-128.
RX PubMed=15831457; DOI=10.1128/mcb.25.9.3506-3518.2005;
RA Ihara M., Yamamoto H., Kikuchi A.;
RT "SUMO-1 modification of PIASy, an E3 ligase, is necessary for PIASy-
RT dependent activation of Tcf-4.";
RL Mol. Cell. Biol. 25:3506-3518(2005).
RN [13]
RP FUNCTION IN SUMOYLATION OF PARK7, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=15976810; DOI=10.1038/sj.cdd.4401704;
RA Shinbo Y., Niki T., Taira T., Ooe H., Takahashi-Niki K., Maita C.,
RA Seino C., Iguchi-Ariga S.M.M., Ariga H.;
RT "Proper SUMO-1 conjugation is essential to DJ-1 to exert its full
RT activities.";
RL Cell Death Differ. 13:96-108(2006).
RN [14]
RP INTERACTION WITH KLF8.
RX PubMed=16617055; DOI=10.1074/jbc.m513135200;
RA Wei H., Wang X., Gan B., Urvalek A.M., Melkoumian Z.K., Guan J.-L.,
RA Zhao J.;
RT "Sumoylation delimits KLF8 transcriptional activity associated with the
RT cell cycle regulation.";
RL J. Biol. Chem. 281:16664-16671(2006).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP FUNCTION, PATHWAY, AND INTERACTION WITH MTA1.
RX PubMed=21965678; DOI=10.1074/jbc.m111.267237;
RA Cong L., Pakala S.B., Ohshiro K., Li D.Q., Kumar R.;
RT "SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1
RT (MTA1) synergistically regulate its transcriptional repressor function.";
RL J. Biol. Chem. 286:43793-43808(2011).
RN [18]
RP FUNCTION IN SUMOYLATION OF HERC2 AND RNF168, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=22508508; DOI=10.1083/jcb.201106152;
RA Danielsen J.R., Povlsen L.K., Villumsen B.H., Streicher W., Nilsson J.,
RA Wikstrom M., Bekker-Jensen S., Mailand N.;
RT "DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a
RT novel SUMO-binding Zinc finger.";
RL J. Cell Biol. 197:179-187(2012).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-59, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [20]
RP INTERACTION WITH PRDM1.
RX PubMed=28842558; DOI=10.1038/s41467-017-00476-w;
RA Wang W.F., Yan L., Liu Z., Liu L.X., Lin J., Liu Z.Y., Chen X.P., Zhang W.,
RA Xu Z.Z., Shi T., Li J.M., Zhao Y.L., Meng G., Xia Y., Li J.Y., Zhu J.;
RT "HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal
RT misfolded Blimp-1s in lymphoma cells.";
RL Nat. Commun. 8:363-363(2017).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-9; LYS-35; LYS-56; LYS-59;
RP LYS-68; LYS-69 AND LYS-125, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=32832608; DOI=10.1126/sciadv.aba7822;
RA Gao S.S., Guan H., Yan S., Hu S., Song M., Guo Z.P., Xie D.F., Liu Y.,
RA Liu X., Zhang S., Zhou P.K.;
RT "TIP60 K430 SUMOylation attenuates its interaction with DNA-PKcs in S-phase
RT cells: Facilitating homologous recombination and emerging target for cancer
RT therapy.";
RL Sci. Adv. 6:eaba7822-eaba7822(2020).
CC -!- FUNCTION: Functions as an E3-type small ubiquitin-like modifier (SUMO)
CC ligase, stabilizing the interaction between UBE2I and the substrate,
CC and as a SUMO-tethering factor (PubMed:12511558, PubMed:12631292,
CC PubMed:12727872, PubMed:15831457, PubMed:15976810, PubMed:22508508,
CC PubMed:32832608). Mediates sumoylation of CEBPA, PARK7, HERC2, MYB,
CC TCF4 and RNF168 (PubMed:12511558, PubMed:12631292, PubMed:12727872,
CC PubMed:15831457, PubMed:15976810, PubMed:22508508). Plays a crucial
CC role as a transcriptional coregulation in various cellular pathways,
CC including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and
CC the steroid hormone signaling pathway (PubMed:11388671). Involved in
CC gene silencing (PubMed:11248056). In Wnt signaling, represses LEF1 and
CC enhances TCF4 transcriptional activities through promoting their
CC sumoylations (PubMed:12727872, PubMed:15831457). Enhances the
CC sumoylation of MTA1 and may participate in its paralog-selective
CC sumoylation (PubMed:21965678). Binds to AT-rich DNA sequences, known as
CC matrix or scaffold attachment regions (MARs/SARs) (By similarity).
CC Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage,
CC facilitating repair of DNA double-strand breaks (DSBs) via homologous
CC recombination (HR) (PubMed:32832608). {ECO:0000250|UniProtKB:Q9JM05,
CC ECO:0000269|PubMed:11248056, ECO:0000269|PubMed:11388671,
CC ECO:0000269|PubMed:12511558, ECO:0000269|PubMed:12631292,
CC ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:15831457,
CC ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:21965678,
CC ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:32832608}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:12511558,
CC ECO:0000269|PubMed:12631292, ECO:0000269|PubMed:12727872,
CC ECO:0000269|PubMed:15831457, ECO:0000269|PubMed:15976810,
CC ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:32832608};
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000269|PubMed:12511558, ECO:0000269|PubMed:12631292,
CC ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:15831457,
CC ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:21965678,
CC ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:32832608}.
CC -!- SUBUNIT: Interacts with AR, AXIN1, GATA2, LEF1, TP53 and STAT1 (IFNG-
CC induced) (PubMed:11248056, PubMed:11388671, PubMed:11439351,
CC PubMed:12223491, PubMed:12750312). Interacts with TICAM1
CC (PubMed:15251447). Interacts with KLF8; the interaction results in SUMO
CC ligation and repression of KLF8 transcriptional activity and of its
CC cell cycle progression into G(1) phase (PubMed:16617055). Interacts
CC with MTA1 (PubMed:21965678). Interacts with PRDM1/Blimp-1
CC (PubMed:28842558). Interacts with TRIM32 upon treatment with UVB and
CC TNF-alpha (By similarity). {ECO:0000250|UniProtKB:Q9JM05,
CC ECO:0000269|PubMed:11248056, ECO:0000269|PubMed:11388671,
CC ECO:0000269|PubMed:11439351, ECO:0000269|PubMed:12223491,
CC ECO:0000269|PubMed:12750312, ECO:0000269|PubMed:15251447,
CC ECO:0000269|PubMed:16617055, ECO:0000269|PubMed:21965678,
CC ECO:0000269|PubMed:28842558}.
CC -!- INTERACTION:
CC Q8N2W9; O43865: AHCYL1; NbExp=3; IntAct=EBI-473160, EBI-2371423;
CC Q8N2W9; P05067: APP; NbExp=3; IntAct=EBI-473160, EBI-77613;
CC Q8N2W9; Q14457: BECN1; NbExp=3; IntAct=EBI-473160, EBI-949378;
CC Q8N2W9; Q96IK1-2: BOD1; NbExp=3; IntAct=EBI-473160, EBI-18924329;
CC Q8N2W9; Q9BSJ5: C17orf80; NbExp=3; IntAct=EBI-473160, EBI-2872520;
CC Q8N2W9; P27797: CALR; NbExp=3; IntAct=EBI-473160, EBI-1049597;
CC Q8N2W9; Q8N5S9-2: CAMKK1; NbExp=3; IntAct=EBI-473160, EBI-25850646;
CC Q8N2W9; Q6ZP82: CCDC141; NbExp=3; IntAct=EBI-473160, EBI-928795;
CC Q8N2W9; P12830: CDH1; NbExp=3; IntAct=EBI-473160, EBI-727477;
CC Q8N2W9; Q15078: CDK5R1; NbExp=3; IntAct=EBI-473160, EBI-746189;
CC Q8N2W9; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-473160, EBI-2872414;
CC Q8N2W9; P36957: DLST; NbExp=3; IntAct=EBI-473160, EBI-351007;
CC Q8N2W9; O00472: ELL2; NbExp=3; IntAct=EBI-473160, EBI-395274;
CC Q8N2W9; P11474: ESRRA; NbExp=3; IntAct=EBI-473160, EBI-372412;
CC Q8N2W9; Q6P1L5: FAM117B; NbExp=3; IntAct=EBI-473160, EBI-3893327;
CC Q8N2W9; Q8TAK5: GABPB2; NbExp=3; IntAct=EBI-473160, EBI-8468945;
CC Q8N2W9; F2Z2M7: GALNT10; NbExp=3; IntAct=EBI-473160, EBI-23893155;
CC Q8N2W9; P15976-2: GATA1; NbExp=3; IntAct=EBI-473160, EBI-9090198;
CC Q8N2W9; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-473160, EBI-347538;
CC Q8N2W9; Q16665: HIF1A; NbExp=3; IntAct=EBI-473160, EBI-447269;
CC Q8N2W9; P09017: HOXC4; NbExp=3; IntAct=EBI-473160, EBI-3923226;
CC Q8N2W9; P42858: HTT; NbExp=6; IntAct=EBI-473160, EBI-466029;
CC Q8N2W9; P80217-2: IFI35; NbExp=3; IntAct=EBI-473160, EBI-12823003;
CC Q8N2W9; Q9UKP3-2: ITGB1BP2; NbExp=3; IntAct=EBI-473160, EBI-25856470;
CC Q8N2W9; Q8WZ19: KCTD13; NbExp=3; IntAct=EBI-473160, EBI-742916;
CC Q8N2W9; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-473160, EBI-2796400;
CC Q8N2W9; Q92615: LARP4B; NbExp=3; IntAct=EBI-473160, EBI-1052558;
CC Q8N2W9; Q5T752: LCE1D; NbExp=3; IntAct=EBI-473160, EBI-11741311;
CC Q8N2W9; Q14693: LPIN1; NbExp=3; IntAct=EBI-473160, EBI-5278370;
CC Q8N2W9; Q8TD91-2: MAGEC3; NbExp=3; IntAct=EBI-473160, EBI-10694180;
CC Q8N2W9; Q9NP98: MYOZ1; NbExp=3; IntAct=EBI-473160, EBI-744402;
CC Q8N2W9; I6L9F6: NEFL; NbExp=3; IntAct=EBI-473160, EBI-10178578;
CC Q8N2W9; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-473160, EBI-1055945;
CC Q8N2W9; O60551: NMT2; NbExp=3; IntAct=EBI-473160, EBI-3920273;
CC Q8N2W9; P09874: PARP1; NbExp=5; IntAct=EBI-473160, EBI-355676;
CC Q8N2W9; P57052: RBM11; NbExp=3; IntAct=EBI-473160, EBI-741332;
CC Q8N2W9; Q04206: RELA; NbExp=2; IntAct=EBI-473160, EBI-73886;
CC Q8N2W9; O75446: SAP30; NbExp=3; IntAct=EBI-473160, EBI-632609;
CC Q8N2W9; O60902-3: SHOX2; NbExp=3; IntAct=EBI-473160, EBI-9092164;
CC Q8N2W9; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-473160, EBI-358489;
CC Q8N2W9; Q86W54-2: SPATA24; NbExp=3; IntAct=EBI-473160, EBI-12041693;
CC Q8N2W9; P61956: SUMO2; NbExp=3; IntAct=EBI-473160, EBI-473220;
CC Q8N2W9; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-473160, EBI-11123832;
CC Q8N2W9; O75528: TADA3; NbExp=2; IntAct=EBI-473160, EBI-473249;
CC Q8N2W9; P04637: TP53; NbExp=2; IntAct=EBI-473160, EBI-366083;
CC Q8N2W9; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-473160, EBI-11952721;
CC Q8N2W9; O00635: TRIM38; NbExp=3; IntAct=EBI-473160, EBI-2130415;
CC Q8N2W9; Q9NX94: WBP1L; NbExp=3; IntAct=EBI-473160, EBI-10316321;
CC Q8N2W9; Q8NCN2: ZBTB34; NbExp=3; IntAct=EBI-473160, EBI-11317716;
CC Q8N2W9; O95789-4: ZMYM6; NbExp=3; IntAct=EBI-473160, EBI-12949277;
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000269|PubMed:11248056,
CC ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:15831457}.
CC Note=Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML
CC (promyelocytic leukemia) nuclear bodies. {ECO:0000269|PubMed:12727872,
CC ECO:0000269|PubMed:15831457}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and, at lower levels, in
CC spleen, prostate, ovary, colon and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:11439351}.
CC -!- DOMAIN: The LXXLL motif is a coregulator signature that is essential
CC for transcriptional corepression. {ECO:0000269|PubMed:11248056}.
CC -!- PTM: Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is
CC required for TCF4 sumoylation and transcriptional activation. Represses
CC LEF1 transcriptional activity. SUMO1 is the preferred conjugate.
CC {ECO:0000269|PubMed:15831457}.
CC -!- SIMILARITY: Belongs to the PIAS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD45155.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF077952; AAC36703.1; -; mRNA.
DR EMBL; BC010047; AAH10047.2; -; mRNA.
DR EMBL; BC029874; AAH29874.1; -; mRNA.
DR EMBL; BC066895; AAH66895.1; -; mRNA.
DR EMBL; AF164437; AAD45155.1; ALT_INIT; mRNA.
DR CCDS; CCDS12118.1; -.
DR RefSeq; NP_056981.2; NM_015897.3.
DR AlphaFoldDB; Q8N2W9; -.
DR SMR; Q8N2W9; -.
DR BioGRID; 119624; 154.
DR DIP; DIP-32499N; -.
DR ELM; Q8N2W9; -.
DR IntAct; Q8N2W9; 106.
DR MINT; Q8N2W9; -.
DR STRING; 9606.ENSP00000262971; -.
DR iPTMnet; Q8N2W9; -.
DR PhosphoSitePlus; Q8N2W9; -.
DR BioMuta; PIAS4; -.
DR DMDM; 34922831; -.
DR EPD; Q8N2W9; -.
DR jPOST; Q8N2W9; -.
DR MassIVE; Q8N2W9; -.
DR MaxQB; Q8N2W9; -.
DR PaxDb; Q8N2W9; -.
DR PeptideAtlas; Q8N2W9; -.
DR PRIDE; Q8N2W9; -.
DR ProteomicsDB; 71739; -.
DR Antibodypedia; 1762; 365 antibodies from 37 providers.
DR DNASU; 51588; -.
DR Ensembl; ENST00000262971.3; ENSP00000262971.1; ENSG00000105229.7.
DR GeneID; 51588; -.
DR KEGG; hsa:51588; -.
DR MANE-Select; ENST00000262971.3; ENSP00000262971.1; NM_015897.4; NP_056981.2.
DR UCSC; uc002lzg.4; human.
DR CTD; 51588; -.
DR DisGeNET; 51588; -.
DR GeneCards; PIAS4; -.
DR HGNC; HGNC:17002; PIAS4.
DR HPA; ENSG00000105229; Low tissue specificity.
DR MIM; 605989; gene.
DR neXtProt; NX_Q8N2W9; -.
DR OpenTargets; ENSG00000105229; -.
DR PharmGKB; PA134945903; -.
DR VEuPathDB; HostDB:ENSG00000105229; -.
DR eggNOG; KOG2169; Eukaryota.
DR GeneTree; ENSGT01030000234539; -.
DR HOGENOM; CLU_020768_1_1_1; -.
DR InParanoid; Q8N2W9; -.
DR OMA; YETRYNK; -.
DR OrthoDB; 1205949at2759; -.
DR PhylomeDB; Q8N2W9; -.
DR TreeFam; TF323787; -.
DR PathwayCommons; Q8N2W9; -.
DR Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-3232118; SUMOylation of transcription factors.
DR Reactome; R-HSA-3232142; SUMOylation of ubiquitinylation proteins.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-4085377; SUMOylation of SUMOylation proteins.
DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins.
DR Reactome; R-HSA-4755510; SUMOylation of immune response proteins.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR SignaLink; Q8N2W9; -.
DR SIGNOR; Q8N2W9; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 51588; 34 hits in 1104 CRISPR screens.
DR ChiTaRS; PIAS4; human.
DR GeneWiki; PIAS4; -.
DR GenomeRNAi; 51588; -.
DR Pharos; Q8N2W9; Tbio.
DR PRO; PR:Q8N2W9; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8N2W9; protein.
DR Bgee; ENSG00000105229; Expressed in left testis and 140 other tissues.
DR Genevisible; Q8N2W9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0016363; C:nuclear matrix; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:1990234; C:transferase complex; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0061665; F:SUMO ligase activity; IDA:UniProtKB.
DR GO; GO:0019789; F:SUMO transferase activity; IMP:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0060887; P:limb epidermis development; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:1902174; P:positive regulation of keratinocyte apoptotic process; ISS:BHF-UCL.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0042359; P:vitamin D metabolic process; TAS:Reactome.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.10.720.30; -; 1.
DR Gene3D; 2.60.120.780; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR027224; PIAS4.
DR InterPro; IPR023321; PINIT.
DR InterPro; IPR038654; PINIT_sf.
DR InterPro; IPR003034; SAP_dom.
DR InterPro; IPR036361; SAP_dom_sf.
DR InterPro; IPR004181; Znf_MIZ.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR10782:SF9; PTHR10782:SF9; 1.
DR Pfam; PF14324; PINIT; 1.
DR Pfam; PF02891; zf-MIZ; 1.
DR SMART; SM00513; SAP; 1.
DR SUPFAM; SSF68906; SSF68906; 1.
DR PROSITE; PS51466; PINIT; 1.
DR PROSITE; PS50800; SAP; 1.
DR PROSITE; PS51044; ZF_SP_RING; 1.
PE 1: Evidence at protein level;
KW Acetylation; DNA-binding; Isopeptide bond; Metal-binding; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Wnt signaling pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..510
FT /note="E3 SUMO-protein ligase PIAS4"
FT /id="PRO_0000218982"
FT DOMAIN 12..46
FT /note="SAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT DOMAIN 119..279
FT /note="PINIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00799"
FT ZN_FING 311..392
FT /note="SP-RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT REGION 443..510
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 20..24
FT /note="LXXLL motif"
FT /evidence="ECO:0000269|PubMed:11248056"
FT COMPBIAS 473..491
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 342
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 365
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 368
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 114
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 9
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 35
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000269|PubMed:15831457"
FT CROSSLNK 35
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 56
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 59
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 68
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 69
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 125
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 128
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:15831457"
FT MUTAGEN 23..24
FT /note="LL->AA: Loss of repression of AR- and STAT1-induced
FT transcription; no effect on AR- and STAT1-binding."
FT /evidence="ECO:0000269|PubMed:11248056,
FT ECO:0000269|PubMed:11439351"
FT MUTAGEN 35
FT /note="K->R: Complete loss of sumoylation. No enhancement
FT of TCF4 sumoylation. No effect on interaction with TCF4.
FT Colocalizes with SUMO1 in nucleus but concentrated into
FT nuclear granules."
FT /evidence="ECO:0000269|PubMed:12727872,
FT ECO:0000269|PubMed:15831457"
FT MUTAGEN 128
FT /note="K->R: Some loss of sumoylation."
FT /evidence="ECO:0000269|PubMed:12727872,
FT ECO:0000269|PubMed:15831457"
FT MUTAGEN 342
FT /note="C->A: Inhibits TCF4 sumoylation. Inhibits beta-
FT catenin-mediated TCF7L2/TCF4 activity. No colocalization
FT with TCF7L2/TCF4 in nuclear punctate structures; when
FT associated with A-347."
FT /evidence="ECO:0000269|PubMed:12727872"
FT MUTAGEN 347
FT /note="C->A: Inhibits TCF4 sumoylation. Inhibits beta-
FT catenin-mediated TCF7L2/TCF4 activity. No colocalization
FT with TCF7L2/TCF4 in nuclear punctate structures; when
FT associated with A-342. AR- and STAT1-binding."
FT /evidence="ECO:0000269|PubMed:12727872"
FT CONFLICT 178
FT /note="N -> K (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 179..182
FT /note="SREL -> FQGM (in Ref. 1 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="E -> G (in Ref. 2; AAH66895)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 510 AA; 56504 MW; 26AAA18246E1ACE3 CRC64;
MAAELVEAKN MVMSFRVSDL QMLLGFVGRS KSGLKHELVT RALQLVQFDC SPELFKKIKE
LYETRYAKKN SEPAPQPHRP LDPLTMHSTY DRAGAVPRTP LAGPNIDYPV LYGKYLNGLG
RLPAKTLKPE VRLVKLPFFN MLDELLKPTE LVPQNNEKLQ ESPCIFALTP RQVELIRNSR
ELQPGVKAVQ VVLRICYSDT SCPQEDQYPP NIAVKVNHSY CSVPGYYPSN KPGVEPKRPC
RPINLTHLMY LSSATNRITV TWGNYGKSYS VALYLVRQLT SSELLQRLKT IGVKHPELCK
ALVKEKLRLD PDSEIATTGV RVSLICPLVK MRLSVPCRAE TCAHLQCFDA VFYLQMNEKK
PTWMCPVCDK PAPYDQLIID GLLSKILSEC EDADEIEYLV DGSWCPIRAE KERSCSPQGA
ILVLGPSDAN GLLPAPSVNG SGALGSTGGG GPVGSMENGK PGADVVDLTL DSSSSSEDEE
EEEEEEEDED EEGPRPKRRC PFQKGLVPAC
