PIAS3_RAT
ID PIAS3_RAT Reviewed; 628 AA.
AC O70260;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=E3 SUMO-protein ligase PIAS3;
DE EC=2.3.2.-;
DE AltName: Full=E3 SUMO-protein transferase PIAS3 {ECO:0000305};
DE AltName: Full=KChAP;
DE AltName: Full=Potassium channel-associated protein;
DE AltName: Full=Protein inhibitor of activated STAT protein 3;
GN Name=Pias3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9565597; DOI=10.1074/jbc.273.19.11745;
RA Wible B.A., Yang Q., Kuryshev Y.A., Accili E.A., Brown A.M.;
RT "Cloning and expression of a novel K+ channel regulatory protein, KChAP.";
RL J. Biol. Chem. 273:11745-11751(1998).
RN [2]
RP INTERACTION WITH MITF.
RX PubMed=11709556; DOI=10.1074/jbc.m109236200;
RA Levy C., Nechushtan H., Razin E.;
RT "A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia
RT transcription factor.";
RL J. Biol. Chem. 277:1962-1966(2002).
RN [3]
RP INTERACTION WITH STAT5.
RX PubMed=11997457; DOI=10.1073/pnas.092160699;
RA Rycyzyn M.A., Clevenger C.V.;
RT "The intranuclear prolactin/cyclophilin B complex as a transcriptional
RT inducer.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6790-6795(2002).
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 coregulation in various cellular pathways, including
CC the STAT pathway and the steroid hormone signaling pathway. The effects
CC of this transcriptional coregulation, transactivation or silencing, may
CC vary depending upon the biological context. Enhances the sumoylation of
CC MTA1 and may participate in its paralog-selective sumoylation.
CC Sumoylates CCAR2 which promotes its interaction with SIRT1. Diminishes
CC the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with
CC SUMO1 in the nucleus (By similarity). {ECO:0000250|UniProtKB:O54714,
CC ECO:0000250|UniProtKB:Q9Y6X2}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Binds SUMO1 and UBE2I. Interacts with AR, BCL11A, GFI1, HMGA2,
CC IRF1, MITF, NCOA2, as well as with STAT3, after treatment with IL6,
CC CNTF or OSM and with STAT5, after PRL stimulation. Interacts with PLAG1
CC (By similarity). Interacts with ZFHX3. Interacts with MTA1. Interacts
CC with CCAR2 (via N-terminus) (By similarity). Interacts with TRIM8 (By
CC similarity). Interacts with PRDM1 (By similarity).
CC {ECO:0000250|UniProtKB:O54714, ECO:0000250|UniProtKB:Q9Y6X2}.
CC -!- INTERACTION:
CC O70260; P42260: Grik2; NbExp=3; IntAct=EBI-7974636, EBI-7809795;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O54714}. Nucleus
CC {ECO:0000269|PubMed:9565597}. Nucleus speckle
CC {ECO:0000250|UniProtKB:O54714}. Note=Colocalizes with MITF in the
CC nucleus. Colocalizes with GFI1 in nuclear dots. Colocalizes with SUMO1
CC in nuclear granules. {ECO:0000250|UniProtKB:O54714}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in lung,
CC kidney and spleen. {ECO:0000269|PubMed:9565597}.
CC -!- DOMAIN: The LXXLL motif is a transcriptional coregulator signature.
CC -!- PTM: Sumoylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PIAS family. {ECO:0000305}.
CC -!- CAUTION: Has been shown to interact with voltage-gated potassium
CC channels, including the KCNB1 subunit, and to be critical for current
CC enhancement. However, in view of its mostly nuclear subcellular
CC location and its established function as a transcriptional coregulator,
CC promoting the sumoylation of several transcription factors, the effect
CC on potassium channels awaits further experimental confirmation.
CC {ECO:0000305}.
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DR EMBL; AF032872; AAC40114.4; -; mRNA.
DR RefSeq; NP_113972.2; NM_031784.2.
DR AlphaFoldDB; O70260; -.
DR SMR; O70260; -.
DR BioGRID; 249779; 1.
DR DIP; DIP-47656N; -.
DR IntAct; O70260; 4.
DR MINT; O70260; -.
DR STRING; 10116.ENSRNOP00000028814; -.
DR TCDB; 8.A.15.1.1; the k(+) channel accessory protein (kchap) family.
DR iPTMnet; O70260; -.
DR PhosphoSitePlus; O70260; -.
DR PaxDb; O70260; -.
DR GeneID; 83614; -.
DR KEGG; rno:83614; -.
DR UCSC; RGD:708413; rat.
DR CTD; 10401; -.
DR RGD; 708413; Pias3.
DR VEuPathDB; HostDB:ENSRNOG00000021218; -.
DR eggNOG; KOG2169; Eukaryota.
DR InParanoid; O70260; -.
DR OMA; HYMSPLT; -.
DR OrthoDB; 1205949at2759; -.
DR PhylomeDB; O70260; -.
DR TreeFam; TF323787; -.
DR Reactome; R-RNO-3232118; SUMOylation of transcription factors.
DR Reactome; R-RNO-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-RNO-4615885; SUMOylation of DNA replication proteins.
DR Reactome; R-RNO-4755510; SUMOylation of immune response proteins.
DR Reactome; R-RNO-5696395; Formation of Incision Complex in GG-NER.
DR UniPathway; UPA00886; -.
DR PRO; PR:O70260; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000021218; Expressed in pancreas and 20 other tissues.
DR ExpressionAtlas; O70260; baseline and differential.
DR Genevisible; O70260; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:RGD.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IDA:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; IDA:RGD.
DR GO; GO:0061665; F:SUMO ligase activity; IBA:GO_Central.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:RGD.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0033234; P:negative regulation of protein sumoylation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:RGD.
DR GO; GO:0045838; P:positive regulation of membrane potential; IDA:RGD.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISO:RGD.
DR GO; GO:0016925; P:protein sumoylation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0071847; P:TNFSF11-mediated signaling pathway; ISO:RGD.
DR Gene3D; 1.10.720.30; -; 1.
DR Gene3D; 2.60.120.780; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR027226; PIAS3.
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:SF10; PTHR10782:SF10; 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 Cytoplasm; Isopeptide bond; Metal-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..628
FT /note="E3 SUMO-protein ligase PIAS3"
FT /id="PRO_0000218981"
FT DOMAIN 11..45
FT /note="SAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT DOMAIN 115..280
FT /note="PINIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00799"
FT ZN_FING 312..393
FT /note="SP-RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT REGION 1..200
FT /note="Interaction with CCAR2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X2"
FT REGION 72..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..460
FT /note="SUMO1-binding"
FT /evidence="ECO:0000250"
FT REGION 573..618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 19..23
FT /note="LXXLL motif"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 345
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 366
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT BINDING 369
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00452"
FT CROSSLNK 46
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X2"
FT CROSSLNK 56
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X2"
FT CROSSLNK 230
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X2"
FT CROSSLNK 307
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X2"
FT CROSSLNK 466
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X2"
FT CROSSLNK 482
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X2"
SQ SEQUENCE 628 AA; 68364 MW; 6710FD5F0AEB13FD CRC64;
MAELGELKHM VMSFRVSELQ VLLGFAGRNK SGRKHELLAK ALHLLKSSCA PSVQMKIKEL
YRRRFPRKTL GPSDLSLLSL PPGTSPVGSP SPLASIPPTL LTPGTLLGPK REVDMHPPLP
QPVHPDVTMK PLPFYEVYGE LIRPTTLAST SSQRFEEAHF TFALTPQQLQ QILTSREVLP
GAKCDYTIQV QLRFCLCETS CPQEDYFPPN LFVKVNGKLC PLPGYLPPTK NGAEPKRPSR
PINITPLARL SATVPNTIVV NWSSEFGRNY SLSVYLVRQL TAGTLLQKLR AKGIRNPDHS
RALIKEKLTA DPDSEVATTS LRVSLMCPLG KMRLTVPCRA LTCAHLQSFD AALYLQMNEK
KPTWTCPVCD KKAPYESLII DGLFMEILNS CSDCDEIQFM EDGSWCPMKP KKEASEVCPP
PGYGLDGLQY SPVQEGNQSE NKKRVEVIDL TIESSSDEED LPPTKKHCPV TSAAIPALPG
SKGALTSGHQ PSSVLRSPAM GTLGSDFLSS LPLHEYPPAF PLGADIQGLD LFSFLQTESQ
HYSPSVITSL DEQDTLGHFF QFRGTPPHFL GPLAPTLGSS HRSATPAPAP GRVSSIVAPG
SSLREGHGGP LPSGPSLTGC RSDVISLD
