PIAS2_HUMAN
ID PIAS2_HUMAN Reviewed; 621 AA.
AC O75928; O75927; Q96BT5; Q96KE3;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=E3 SUMO-protein ligase PIAS2;
DE EC=2.3.2.-;
DE AltName: Full=Androgen receptor-interacting protein 3;
DE Short=ARIP3;
DE AltName: Full=DAB2-interacting protein;
DE Short=DIP;
DE AltName: Full=E3 SUMO-protein transferase PIAS2 {ECO:0000305};
DE AltName: Full=Msx-interacting zinc finger protein;
DE Short=Miz1;
DE AltName: Full=PIAS-NY protein;
DE AltName: Full=Protein inhibitor of activated STAT x;
DE AltName: Full=Protein inhibitor of activated STAT2;
GN Name=PIAS2; Synonyms=PIASX;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PIAS2-ALPHA AND PIAS2-BETA).
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 [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Testis;
RX PubMed=15301740;
RA Zheng Y., Zhou Z.-M., Yin L.-L., Li J.-M., Sha J.-H.;
RT "Molecular cloning and characterization of a novel splicing variant of
RT PIASx.";
RL Acta Pharmacol. Sin. 25:1058-1064(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PIAS2-ALPHA).
RC TISSUE=Brain;
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=9920921; DOI=10.1074/jbc.274.6.3700;
RA Moilanen A.-M., Karvonen U., Poukka H., Yan W., Toppari J., Jaenne O.A.,
RA Palvimo J.J.;
RT "A testis-specific androgen receptor coregulator that belongs to a novel
RT family of nuclear proteins.";
RL J. Biol. Chem. 274:3700-3704(1999).
RN [6]
RP INTERACTION WITH SUMO1; TP73 AND TP53.
RX PubMed=10961991; DOI=10.1074/jbc.m004293200;
RA Minty A., Dumont X., Kaghad M., Caput D.;
RT "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73
RT identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction
RT motif.";
RL J. Biol. Chem. 275:36316-36323(2000).
RN [7]
RP INTERACTION WITH PARK7, AND SUBCELLULAR LOCATION.
RX PubMed=11477070; DOI=10.1074/jbc.m101730200;
RA Takahashi K., Taira T., Niki T., Seino C., Iguchi-Ariga S.M.M., Ariga H.;
RT "DJ-1 positively regulates the androgen receptor by impairing the binding
RT of PIASx alpha to the receptor.";
RL J. Biol. Chem. 276:37556-37563(2001).
RN [8]
RP TISSUE SPECIFICITY.
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 [9]
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 [10]
RP SUMOYLATION OF MDM2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-362.
RX PubMed=12393906; DOI=10.1074/jbc.m208319200;
RA Miyauchi Y., Yogosawa S., Honda R., Nishida T., Yasuda H.;
RT "Sumoylation of Mdm2 by protein inhibitor of activated STAT (PIAS) and
RT RanBP2 enzymes.";
RL J. Biol. Chem. 277:50131-50136(2002).
RN [11]
RP INTERACTION WITH JUN; TP53 AND UBE2I, SUMOYLATION, AND MUTAGENESIS OF
RP CYS-362.
RX PubMed=11867732; DOI=10.1073/pnas.052559499;
RA Schmidt D., Mueller S.;
RT "Members of the PIAS family act as SUMO ligases for c-Jun and p53 and
RT repress p53 activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2872-2877(2002).
RN [12]
RP INTERACTION WITH STAT4, AND SUBCELLULAR LOCATION.
RX PubMed=12716907; DOI=10.1074/jbc.c300119200;
RA Arora T., Liu B., He H., Kim J., Murphy T.L., Murphy K.M., Modlin R.L.,
RA Shuai K.;
RT "PIASx is a transcriptional co-repressor of signal transducer and activator
RT of transcription 4.";
RL J. Biol. Chem. 278:21327-21330(2003).
RN [13]
RP INTERACTION WITH PLAG1.
RX PubMed=15208321; DOI=10.1074/jbc.m401753200;
RA Van Dyck F., Delvaux E.L.D., Van de Ven W.J.M., Chavez M.V.;
RT "Repression of the transactivating capacity of the oncoprotein PLAG1 by
RT SUMOylation.";
RL J. Biol. Chem. 279:36121-36131(2004).
RN [14]
RP FUNCTION, AND INTERACTION WITH ELK1.
RX PubMed=15920481; DOI=10.1038/sj.emboj.7600690;
RA Yang S.-H., Sharrocks A.D.;
RT "PIASx acts as an Elk-1 coactivator by facilitating derepression.";
RL EMBO J. 24:2161-2171(2005).
RN [15]
RP FUNCTION IN PARK7 SUMOYLATION.
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 [16]
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 [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP INTERACTION WITH IFIH1/MDA5.
RX PubMed=21156324; DOI=10.1016/j.molimm.2010.09.003;
RA Fu J., Xiong Y., Xu Y., Cheng G., Tang H.;
RT "MDA5 is SUMOylated by PIAS2? in the upregulation of type I interferon
RT signaling.";
RL Mol. Immunol. 48:415-422(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-476; SER-477 AND SER-478, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=22406621; DOI=10.1158/0008-5472.can-11-3159;
RA Rabellino A., Carter B., Konstantinidou G., Wu S.Y., Rimessi A.,
RA Byers L.A., Heymach J.V., Girard L., Chiang C.M., Teruya-Feldstein J.,
RA Scaglioni P.P.;
RT "The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its
RT oncogenic counterpart PML-RARA.";
RL Cancer Res. 72:2275-2284(2012).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-249 AND LYS-443, AND
RP IDENTIFICATION BY MASS 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 [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-249; LYS-430; LYS-443 AND
RP LYS-489, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-249, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [24]
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 [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-46; LYS-249; LYS-430; LYS-435;
RP LYS-443; LYS-452; LYS-489 AND LYS-502, SUMOYLATION [LARGE SCALE ANALYSIS]
RP AT LYS-562 (ISOFORM PIAS2-ALPHA), AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE 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 [26]
RP STRUCTURE BY NMR OF 466-488 IN COMPLEX WITH SUMO1, AND MUTAGENESIS OF
RP VAL-467; VAL-469; ILE-470; LEU-472 AND THR-473.
RX PubMed=16204249; DOI=10.1074/jbc.m507059200;
RA Song J., Zhang Z., Hu W., Chen Y.;
RT "Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif:
RT a reversal of the bound orientation.";
RL J. Biol. Chem. 280:40122-40129(2005).
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. Plays a crucial role as a
CC transcriptional coregulator in various cellular pathways, including the
CC STAT pathway, the p53 pathway and the steroid hormone signaling
CC pathway. The effects of this transcriptional coregulation,
CC transactivation or silencing may vary depending upon the biological
CC context and the PIAS2 isoform studied. However, it seems to be mostly
CC involved in gene silencing. Binds to sumoylated ELK1 and enhances its
CC transcriptional activity by preventing recruitment of HDAC2 by ELK1,
CC thus reversing SUMO-mediated repression of ELK1 transactivation
CC activity. Isoform PIAS2-beta, but not isoform PIAS2-alpha, promotes
CC MDM2 sumoylation. Isoform PIAS2-alpha promotes PARK7 sumoylation.
CC Isoform PIAS2-beta promotes NCOA2 sumoylation more efficiently than
CC isoform PIAS2-alpha. Isoform PIAS2-alpha sumoylates PML at'Lys-65' and
CC 'Lys-160'. {ECO:0000269|PubMed:15920481, ECO:0000269|PubMed:15976810,
CC ECO:0000269|PubMed:22406621}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Binds SUMO1 and UBE2I. Interacts with AXIN1, JUN, MDM2, PARK7,
CC TP53 and TP73 isoform alpha, but not TP73 isoform beta. Interacts with
CC STAT4 following IL12 and IFN-alpha stimulation of T-cells. Interacts
CC also with GTF2I, GTF2IRD1, IKFZ1, DAB2 and MSX2, as well as with
CC several steroid receptors, including ESR1, ESR2, NR3C1, PGR, AR, and
CC with NCOA2 (By similarity). Sumoylation of a target protein seems to
CC enhance the interaction. Binds to sumoylated ELK1. Binds DNA, such as
CC CDKN1A promoter, in a sequence-specific manner. Interacts with PLAG1.
CC Interacts with KLF8; the interaction results in SUMO ligation and
CC repression of KLF8 transcriptional activity and of its cell cycle
CC progression into G(1) phase. PIAS2-beta interacts with IFIH1/MDA5.
CC Isoform PIAS2-alpha interacts with PML (isoform PML-12). Interacts with
CC PRDM1/Blimp-1 (PubMed:28842558). {ECO:0000250,
CC ECO:0000269|PubMed:10961991, ECO:0000269|PubMed:11477070,
CC ECO:0000269|PubMed:11867732, ECO:0000269|PubMed:12223491,
CC ECO:0000269|PubMed:12716907, ECO:0000269|PubMed:15208321,
CC ECO:0000269|PubMed:15920481, ECO:0000269|PubMed:16204249,
CC ECO:0000269|PubMed:16617055, ECO:0000269|PubMed:21156324,
CC ECO:0000269|PubMed:22406621, ECO:0000269|PubMed:28842558}.
CC -!- INTERACTION:
CC O75928; Q96HD9: ACY3; NbExp=3; IntAct=EBI-348555, EBI-3916242;
CC O75928; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-348555, EBI-10175300;
CC O75928; O95273: CCNDBP1; NbExp=4; IntAct=EBI-348555, EBI-748961;
CC O75928; P14136: GFAP; NbExp=3; IntAct=EBI-348555, EBI-744302;
CC O75928; Q08379: GOLGA2; NbExp=3; IntAct=EBI-348555, EBI-618309;
CC O75928; P20592: MX2; NbExp=3; IntAct=EBI-348555, EBI-10200618;
CC O75928; P01106: MYC; NbExp=4; IntAct=EBI-348555, EBI-447544;
CC O75928; Q8IVL1: NAV2; NbExp=4; IntAct=EBI-348555, EBI-741200;
CC O75928; O43741: PRKAB2; NbExp=3; IntAct=EBI-348555, EBI-1053424;
CC O75928; P63244: RACK1; NbExp=2; IntAct=EBI-348555, EBI-296739;
CC O75928; Q96T51: RUFY1; NbExp=3; IntAct=EBI-348555, EBI-3941207;
CC O75928; P63165: SUMO1; NbExp=8; IntAct=EBI-348555, EBI-80140;
CC O75928; G2XKQ0: SUMO1P1; NbExp=3; IntAct=EBI-348555, EBI-10175576;
CC O75928; P36406: TRIM23; NbExp=3; IntAct=EBI-348555, EBI-740098;
CC O75928; Q969E8: TSR2; NbExp=3; IntAct=EBI-348555, EBI-746981;
CC O75928; P63279: UBE2I; NbExp=8; IntAct=EBI-348555, EBI-80168;
CC O75928; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-348555, EBI-10180829;
CC O75928; O96006: ZBED1; NbExp=3; IntAct=EBI-348555, EBI-740037;
CC O75928; Q96BR9: ZBTB8A; NbExp=3; IntAct=EBI-348555, EBI-742740;
CC O75928; Q59GP6; NbExp=3; IntAct=EBI-348555, EBI-10243413;
CC O75928-2; P15336: ATF2; NbExp=3; IntAct=EBI-348567, EBI-1170906;
CC O75928-2; Q7Z6I8: C5orf24; NbExp=3; IntAct=EBI-348567, EBI-9995695;
CC O75928-2; P35520: CBS; NbExp=3; IntAct=EBI-348567, EBI-740135;
CC O75928-2; Q9UFW8: CGGBP1; NbExp=3; IntAct=EBI-348567, EBI-723153;
CC O75928-2; P16220: CREB1; NbExp=3; IntAct=EBI-348567, EBI-711855;
CC O75928-2; P17661: DES; NbExp=3; IntAct=EBI-348567, EBI-1055572;
CC O75928-2; Q05D60: DEUP1; NbExp=3; IntAct=EBI-348567, EBI-748597;
CC O75928-2; Q14565: DMC1; NbExp=3; IntAct=EBI-348567, EBI-930865;
CC O75928-2; Q96F86: EDC3; NbExp=3; IntAct=EBI-348567, EBI-997311;
CC O75928-2; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-348567, EBI-371922;
CC O75928-2; Q9BPY3: FAM118B; NbExp=3; IntAct=EBI-348567, EBI-726822;
CC O75928-2; O75344: FKBP6; NbExp=5; IntAct=EBI-348567, EBI-744771;
CC O75928-2; P14136: GFAP; NbExp=6; IntAct=EBI-348567, EBI-744302;
CC O75928-2; Q6ISB3: GRHL2; NbExp=3; IntAct=EBI-348567, EBI-10219092;
CC O75928-2; Q6NT76: HMBOX1; NbExp=3; IntAct=EBI-348567, EBI-2549423;
CC O75928-2; Q9NP66: HMG20A; NbExp=3; IntAct=EBI-348567, EBI-740641;
CC O75928-2; Q9P0W2: HMG20B; NbExp=5; IntAct=EBI-348567, EBI-713401;
CC O75928-2; Q9UGU5: HMGXB4; NbExp=3; IntAct=EBI-348567, EBI-7261162;
CC O75928-2; O60812: HNRNPCL1; NbExp=3; IntAct=EBI-348567, EBI-1046507;
CC O75928-2; Q9BUJ2: HNRNPUL1; NbExp=3; IntAct=EBI-348567, EBI-1018153;
CC O75928-2; Q86YM7: HOMER1; NbExp=3; IntAct=EBI-348567, EBI-746815;
CC O75928-2; Q9UJC3: HOOK1; NbExp=3; IntAct=EBI-348567, EBI-746704;
CC O75928-2; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-348567, EBI-11522367;
CC O75928-2; P20839-3: IMPDH1; NbExp=3; IntAct=EBI-348567, EBI-12188657;
CC O75928-2; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-348567, EBI-14069005;
CC O75928-2; Q5T753: LCE1E; NbExp=3; IntAct=EBI-348567, EBI-11955335;
CC O75928-2; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-348567, EBI-11973993;
CC O75928-2; Q9UH92-3: MLX; NbExp=3; IntAct=EBI-348567, EBI-8852072;
CC O75928-2; P20591: MX1; NbExp=3; IntAct=EBI-348567, EBI-929476;
CC O75928-2; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-348567, EBI-744782;
CC O75928-2; P22234: PAICS; NbExp=3; IntAct=EBI-348567, EBI-712261;
CC O75928-2; O75569: PRKRA; NbExp=3; IntAct=EBI-348567, EBI-713955;
CC O75928-2; P41219: PRPH; NbExp=3; IntAct=EBI-348567, EBI-752074;
CC O75928-2; P48378: RFX2; NbExp=3; IntAct=EBI-348567, EBI-746731;
CC O75928-2; Q06455-2: RUNX1T1; NbExp=5; IntAct=EBI-348567, EBI-11984663;
CC O75928-2; Q15436: SEC23A; NbExp=3; IntAct=EBI-348567, EBI-81088;
CC O75928-2; P35711-4: SOX5; NbExp=3; IntAct=EBI-348567, EBI-11954419;
CC O75928-2; Q9H0A9-2: SPATC1L; NbExp=3; IntAct=EBI-348567, EBI-11995806;
CC O75928-2; Q9BUA3: SPINDOC; NbExp=3; IntAct=EBI-348567, EBI-1773488;
CC O75928-2; P63165: SUMO1; NbExp=3; IntAct=EBI-348567, EBI-80140;
CC O75928-2; Q17R54: SYN3; NbExp=3; IntAct=EBI-348567, EBI-12820047;
CC O75928-2; P07101-3: TH; NbExp=3; IntAct=EBI-348567, EBI-12001016;
CC O75928-2; Q12933: TRAF2; NbExp=3; IntAct=EBI-348567, EBI-355744;
CC O75928-2; Q13114: TRAF3; NbExp=3; IntAct=EBI-348567, EBI-357631;
CC O75928-2; O00463: TRAF5; NbExp=3; IntAct=EBI-348567, EBI-523498;
CC O75928-2; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-348567, EBI-9867283;
CC O75928-2; Q969E8: TSR2; NbExp=3; IntAct=EBI-348567, EBI-746981;
CC O75928-2; P40222: TXLNA; NbExp=3; IntAct=EBI-348567, EBI-359793;
CC O75928-2; Q8TF42: UBASH3B; NbExp=3; IntAct=EBI-348567, EBI-1380492;
CC O75928-2; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-348567, EBI-10180829;
CC O75928-2; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-348567, EBI-741480;
CC O75928-2; Q05516: ZBTB16; NbExp=3; IntAct=EBI-348567, EBI-711925;
CC O75928-2; Q96K80: ZC3H10; NbExp=3; IntAct=EBI-348567, EBI-742550;
CC O75928-2; Q96MM3: ZFP42; NbExp=3; IntAct=EBI-348567, EBI-12151755;
CC O75928-2; Q9P2F9: ZNF319; NbExp=3; IntAct=EBI-348567, EBI-11993110;
CC O75928-2; O60232: ZNRD2; NbExp=3; IntAct=EBI-348567, EBI-741415;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250|UniProtKB:Q8C5D8}.
CC Nucleus, PML body {ECO:0000269|PubMed:12716907,
CC ECO:0000269|PubMed:22406621}. Nucleus {ECO:0000269|PubMed:11477070,
CC ECO:0000269|PubMed:12393906}. Note=Colocalizes at least partially with
CC promyelocytic leukemia nuclear bodies (PML NBs) (PubMed:22406621).
CC Colocalizes with SUMO1 in nuclear granules (By similarity).
CC {ECO:0000250|UniProtKB:Q8C5D8, ECO:0000269|PubMed:22406621}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=PIAS2-beta; Synonyms=PIASx-beta, Miz1;
CC IsoId=O75928-1; Sequence=Displayed;
CC Name=PIAS2-alpha; Synonyms=PIASx-alpha, ARIP3;
CC IsoId=O75928-2; Sequence=VSP_050008, VSP_050009;
CC Name=3;
CC IsoId=O75928-3; Sequence=VSP_012196, VSP_012197;
CC -!- TISSUE SPECIFICITY: Mainly expressed in testis. Isoform 3 is expressed
CC predominantly in adult testis, weakly in pancreas, embryonic testis and
CC sperm, and at very low levels in other organs.
CC {ECO:0000269|PubMed:11439351, ECO:0000269|PubMed:15301740,
CC ECO:0000269|PubMed:9920921}.
CC -!- DEVELOPMENTAL STAGE: Isoform 3 expression in adult testis is 14.2-fold
CC stronger than in embryonic testis. {ECO:0000269|PubMed:15301740}.
CC -!- INDUCTION: Up-regulated transiently during myeloid differentiation in
CC various cells lines, such as HL-60, U-937, K-562, induced by either
CC phorbol ester (TPA) or retinoic acid.
CC -!- DOMAIN: The LXXLL motif is a transcriptional coregulator signature.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:11867732,
CC ECO:0000269|PubMed:12393906}.
CC -!- SIMILARITY: Belongs to the PIAS family. {ECO:0000305}.
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DR EMBL; AF077953; AAC36704.1; -; mRNA.
DR EMBL; AF077954; AAC36705.1; -; mRNA.
DR EMBL; AF361054; AAK48938.1; -; mRNA.
DR EMBL; AC090241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090373; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015190; AAH15190.1; -; mRNA.
DR CCDS; CCDS32824.1; -. [O75928-1]
DR CCDS; CCDS32825.1; -. [O75928-2]
DR RefSeq; NP_001310989.1; NM_001324060.1. [O75928-3]
DR RefSeq; NP_004662.2; NM_004671.4. [O75928-1]
DR RefSeq; NP_775298.1; NM_173206.3. [O75928-2]
DR PDB; 2ASQ; NMR; -; B=466-488.
DR PDB; 4FO9; X-ray; 2.39 A; A=147-488.
DR PDBsum; 2ASQ; -.
DR PDBsum; 4FO9; -.
DR AlphaFoldDB; O75928; -.
DR SMR; O75928; -.
DR BioGRID; 114523; 156.
DR ELM; O75928; -.
DR IntAct; O75928; 112.
DR MINT; O75928; -.
DR STRING; 9606.ENSP00000465676; -.
DR iPTMnet; O75928; -.
DR PhosphoSitePlus; O75928; -.
DR BioMuta; PIAS2; -.
DR EPD; O75928; -.
DR jPOST; O75928; -.
DR MassIVE; O75928; -.
DR MaxQB; O75928; -.
DR PaxDb; O75928; -.
DR PeptideAtlas; O75928; -.
DR PRIDE; O75928; -.
DR ProteomicsDB; 50294; -. [O75928-1]
DR ProteomicsDB; 50295; -. [O75928-2]
DR ProteomicsDB; 50296; -. [O75928-3]
DR Antibodypedia; 9110; 535 antibodies from 41 providers.
DR DNASU; 9063; -.
DR Ensembl; ENST00000324794.11; ENSP00000317163.6; ENSG00000078043.16. [O75928-2]
DR Ensembl; ENST00000585916.6; ENSP00000465676.1; ENSG00000078043.16. [O75928-1]
DR GeneID; 9063; -.
DR KEGG; hsa:9063; -.
DR MANE-Select; ENST00000585916.6; ENSP00000465676.1; NM_004671.5; NP_004662.2.
DR UCSC; uc002lck.4; human. [O75928-1]
DR CTD; 9063; -.
DR DisGeNET; 9063; -.
DR GeneCards; PIAS2; -.
DR HGNC; HGNC:17311; PIAS2.
DR HPA; ENSG00000078043; Tissue enhanced (testis).
DR MIM; 603567; gene.
DR neXtProt; NX_O75928; -.
DR OpenTargets; ENSG00000078043; -.
DR PharmGKB; PA134933292; -.
DR VEuPathDB; HostDB:ENSG00000078043; -.
DR eggNOG; KOG2169; Eukaryota.
DR GeneTree; ENSGT01030000234539; -.
DR HOGENOM; CLU_020768_3_0_1; -.
DR InParanoid; O75928; -.
DR OMA; DPQQYCP; -.
DR OrthoDB; 1205949at2759; -.
DR PhylomeDB; O75928; -.
DR PathwayCommons; O75928; -.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. [O75928-1]
DR Reactome; R-HSA-3232118; SUMOylation of transcription factors. [O75928-1]
DR Reactome; R-HSA-3232142; SUMOylation of ubiquitinylation proteins. [O75928-1]
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors. [O75928-1]
DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-HSA-4551638; SUMOylation of chromatin organization proteins. [O75928-2]
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR SignaLink; O75928; -.
DR SIGNOR; O75928; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 9063; 16 hits in 1114 CRISPR screens.
DR ChiTaRS; PIAS2; human.
DR EvolutionaryTrace; O75928; -.
DR GeneWiki; Protein_inhibitor_of_activated_STAT2; -.
DR GenomeRNAi; 9063; -.
DR Pharos; O75928; Tbio.
DR PRO; PR:O75928; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O75928; protein.
DR Bgee; ENSG00000078043; Expressed in sperm and 207 other tissues.
DR ExpressionAtlas; O75928; baseline and differential.
DR Genevisible; O75928; HS.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0061665; F:SUMO ligase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016925; P:protein sumoylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:Ensembl.
DR DisProt; DP01675; -.
DR Gene3D; 1.10.720.30; -; 1.
DR Gene3D; 2.60.120.780; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00136; -.
DR InterPro; IPR027228; PIAS2.
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:SF12; PTHR10782:SF12; 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 3D-structure; Alternative splicing; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..621
FT /note="E3 SUMO-protein ligase PIAS2"
FT /id="PRO_0000218976"
FT DOMAIN 11..45
FT /note="SAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT DOMAIN 134..299
FT /note="PINIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00799"
FT ZN_FING 331..412
FT /note="SP-RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT REGION 467..473
FT /note="SUMO1-binding"
FT REGION 579..621
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 19..23
FT /note="LXXLL motif"
FT MOTIF 484..492
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 385
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C5D8"
FT CROSSLNK 46
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 443
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 452
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 489
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 502
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..8
FT /note="MADFEELR -> MNAGKQLQRTLH (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15301740"
FT /id="VSP_012196"
FT VAR_SEQ 402..621
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15301740"
FT /id="VSP_012197"
FT VAR_SEQ 551..572
FT /note="LDFLSLIPVDPQYCPPMFLDSL -> EQRRNDINNELKLGTSSDTVQQ (in
FT isoform PIAS2-alpha)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9724754"
FT /id="VSP_050008"
FT VAR_SEQ 573..621
FT /note="Missing (in isoform PIAS2-alpha)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9724754"
FT /id="VSP_050009"
FT VARIANT 207
FT /note="V -> A (in dbSNP:rs16940108)"
FT /id="VAR_056693"
FT MUTAGEN 362
FT /note="C->S,A: Loss of MDM2 and TP53 sumoylation and of
FT autosumoylation; no loss of JUN- and TP53-binding."
FT /evidence="ECO:0000269|PubMed:11867732,
FT ECO:0000269|PubMed:12393906"
FT MUTAGEN 467
FT /note="V->A: Reduces affinity for SUMO1."
FT /evidence="ECO:0000269|PubMed:16204249"
FT MUTAGEN 469
FT /note="V->A: Abolishes binding to SUMO1."
FT /evidence="ECO:0000269|PubMed:16204249"
FT MUTAGEN 470
FT /note="I->A: Abolishes binding to SUMO1."
FT /evidence="ECO:0000269|PubMed:16204249"
FT MUTAGEN 472
FT /note="L->A: Abolishes binding to SUMO1."
FT /evidence="ECO:0000269|PubMed:16204249"
FT MUTAGEN 473
FT /note="T->A: Reduces affinity for SUMO1."
FT /evidence="ECO:0000269|PubMed:16204249"
FT CONFLICT 144
FT /note="P -> L (in Ref. 2; AAK48938)"
FT /evidence="ECO:0000305"
FT CONFLICT 616
FT /note="D -> E (in Ref. 1; AAC36705)"
FT /evidence="ECO:0000305"
FT STRAND 154..165
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 173..181
FT /evidence="ECO:0007829|PDB:4FO9"
FT HELIX 185..192
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 203..215
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:4FO9"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 275..282
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 289..298
FT /evidence="ECO:0007829|PDB:4FO9"
FT HELIX 301..309
FT /evidence="ECO:0007829|PDB:4FO9"
FT HELIX 316..327
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 340..345
FT /evidence="ECO:0007829|PDB:4FO9"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:4FO9"
FT HELIX 370..379
FT /evidence="ECO:0007829|PDB:4FO9"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:4FO9"
FT HELIX 394..396
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 397..400
FT /evidence="ECO:0007829|PDB:4FO9"
FT HELIX 401..407
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 415..418
FT /evidence="ECO:0007829|PDB:4FO9"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:2ASQ"
FT CROSSLNK O75928-2:562
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
SQ SEQUENCE 621 AA; 68240 MW; 6422B383345AD883 CRC64;
MADFEELRNM VSSFRVSELQ VLLGFAGRNK SGRKHDLLMR ALHLLKSGCS PAVQIKIREL
YRRRYPRTLE GLSDLSTIKS SVFSLDGGSS PVEPDLAVAG IHSLPSTSVT PHSPSSPVGS
VLLQDTKPTF EMQQPSPPIP PVHPDVQLKN LPFYDVLDVL IKPTSLVQSS IQRFQEKFFI
FALTPQQVRE ICISRDFLPG GRRDYTVQVQ LRLCLAETSC PQEDNYPNSL CIKVNGKLFP
LPGYAPPPKN GIEQKRPGRP LNITSLVRLS SAVPNQISIS WASEIGKNYS MSVYLVRQLT
SAMLLQRLKM KGIRNPDHSR ALIKEKLTAD PDSEIATTSL RVSLMCPLGK MRLTIPCRAV
TCTHLQCFDA ALYLQMNEKK PTWICPVCDK KAAYESLILD GLFMEILNDC SDVDEIKFQE
DGSWCPMRPK KEAMKVSSQP CTKIESSSVL SKPCSVTVAS EASKKKVDVI DLTIESSSDE
EEDPPAKRKC IFMSETQSSP TKGVLMYQPS SVRVPSVTSV DPAAIPPSLT DYSVPFHHTP
ISSMSSDLPG LDFLSLIPVD PQYCPPMFLD SLTSPLTASS TSVTTTSSHE SSTHVSSSSS
RSETGVITSS GSNIPDIISL D
