Reactome | UniProt:O75928 PIAS2

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UniProt:O75928 PIAS2 Show undefined attributes

chain	chain:1-621
checksum	6422B383345AD883
comment	FUNCTION Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulator in various cellular pathways, including the STAT pathway, the p53 pathway and the steroid hormone signaling pathway. The effects of this transcriptional coregulation, transactivation or silencing may vary depending upon the biological context and the PIAS2 isoform studied. However, it seems to be mostly involved in gene silencing. Binds to sumoylated ELK1 and enhances its transcriptional activity by preventing recruitment of HDAC2 by ELK1, thus reversing SUMO-mediated repression of ELK1 transactivation activity. Isoform PIAS2-beta, but not isoform PIAS2-alpha, promotes MDM2 sumoylation. Isoform PIAS2-alpha promotes PARK7 sumoylation. Isoform PIAS2-beta promotes NCOA2 sumoylation more efficiently than isoform PIAS2-alpha. Isoform PIAS2-alpha sumoylates PML at'Lys-65' and 'Lys-160'.PATHWAY Protein modification; protein sumoylation.SUBUNIT Binds SUMO1 and UBE2I. Interacts with AXIN1, JUN, MDM2, PARK7, TP53 and TP73 isoform alpha, but not TP73 isoform beta. Interacts with STAT4 following IL12 and IFN-alpha stimulation of T-cells. Interacts also with GTF2I, GTF2IRD1, IKFZ1, DAB2 and MSX2, as well as with several steroid receptors, including ESR1, ESR2, NR3C1, PGR, AR, and with NCOA2 (By similarity). Sumoylation of a target protein seems to enhance the interaction. Binds to sumoylated ELK1. Binds DNA, such as CDKN1A promoter, in a sequence-specific manner. Interacts with PLAG1. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase. PIAS2-beta interacts with IFIH1/MDA5. Isoform PIAS2-alpha interacts with PML (isoform PML-12). Interacts with PRDM1/Blimp-1 (PubMed:28842558).INTERACTION Colocalizes at least partially with promyelocytic leukemia nuclear bodies (PML NBs) (PubMed:22406621). Colocalizes with SUMO1 in nuclear granules (By similarity).ALTERNATIVE PRODUCTS Mainly expressed in testis. Isoform 3 is expressed predominantly in adult testis, weakly in pancreas, embryonic testis and sperm, and at very low levels in other organs.DEVELOPMENTAL STAGE Isoform 3 expression in adult testis is 14.2-fold stronger than in embryonic testis.INDUCTION Up-regulated transiently during myeloid differentiation in various cells lines, such as HL-60, U-937, K-562, induced by either phorbol ester (TPA) or retinoic acid.DOMAIN The LXXLL motif is a transcriptional coregulator signature.PTM Sumoylated.SIMILARITY Belongs to the PIAS family.
created	[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
crossReference	[DatabaseIdentifier:12288446] Pharos - Targets:O75928 [DatabaseIdentifier:12332112] RefSeq:NP_001310989.1 [DatabaseIdentifier:12332110] RefSeq:NP_775298.1 [DatabaseIdentifier:12332111] RefSeq:NP_004662.2 [DatabaseIdentifier:11456128] ENSEMBL:ENSG00000078043 [DatabaseIdentifier:11547039] ENSEMBL:ENSP00000317163 [DatabaseIdentifier:11547040] ENSEMBL:ENSP00000465676 [DatabaseIdentifier:11669739] ENSEMBL:ENST00000324794 [DatabaseIdentifier:11669738] ENSEMBL:ENST00000585916 [DatabaseIdentifier:11790605] GeneCards:PIAS2 [DatabaseIdentifier:11806562] GlyGen:O75928 [DatabaseIdentifier:11843609] HPA:ENSG00000078043-PIAS2 [DatabaseIdentifier:12128223] OpenTargets:ENSG00000078043 [DatabaseIdentifier:12203989] PDB:4FO9 [DatabaseIdentifier:12167783] PDB:2ASQ [DatabaseIdentifier:12249690] PRO:O75928
databaseName	UniProt
dbId	242763
description	recommendedName: E3 SUMO-protein ligase PIAS2 ecNumber: 2.3.2.- alternativeName: Androgen receptor-interacting protein 3 shortName: ARIP3 alternativeName: DAB2-interacting protein shortName: DIP alternativeName: fullName evidence="27"E3 SUMO-protein transferase PIAS2 alternativeName: Msx-interacting zinc finger protein shortName: Miz1 alternativeName: PIAS-NY protein alternativeName: Protein inhibitor of activated STAT x alternativeName: Protein inhibitor of activated STAT2
displayName	UniProt:O75928 PIAS2
geneName	PIAS2 PIASX
identifier	O75928
isSequenceChanged	false
keyword	3D-structure Alternative splicing DNA-binding Isopeptide bond Metal-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Transcription Transcription regulation Transferase Ubl conjugation Ubl conjugation pathway Zinc Zinc-finger
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	PIAS2
physicalEntity	[EntityWithAccessionedSequence:R-HSA-2993787] PIAS2 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000078043] ENSEMBL:ENSG00000078043 PIAS2 [ReferenceDNASequence:12728572] UCSC:O75928 PIAS2 [ReferenceDNASequence:11320947] BioGPS Gene:9063 PIAS2 [ReferenceDNASequence:11398187] COSMIC - genes:PIAS2 PIAS2 [ReferenceDNASequence:11418069] CTD Gene:9063 PIAS2 [ReferenceDNASequence:11434978] dbSNP Gene:9063 PIAS2 [ReferenceDNASequence:11822266] HGNC:17311 PIAS2 [ReferenceDNASequence:11863729] KEGG:hsa:9063 PIAS2 [ReferenceDNASequence:11950736] Monarch:9063 PIAS2 [ReferenceDNASequence:12034829] NCBI Gene:9063 PIAS2 [ReferenceDNASequence:12113011] OMIM:603567 PIAS2
referenceTranscript	[ReferenceRNASequence:12514000] RefSeq:NM_173206.4 PIAS2 [ReferenceRNASequence:12514002] RefSeq:NM_004671.5 PIAS2 [ReferenceRNASequence:12514001] RefSeq:NM_001324060.2 PIAS2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	PIAS2_HUMAN O75927 Q96BT5 Q96KE3
sequenceLength	621
species	[Species:48887] Homo sapiens
stId	uniprot:O75928
url	http://purl.uniprot.org/uniprot/O75928

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-2993787] PIAS2 [nucleoplasm]
(isoformParent)	[ReferenceIsoform:uniprot:O75928-2] UniProt:O75928-2 PIAS2 [ReferenceIsoform:uniprot:O75928-1] UniProt:O75928-1 PIAS2
(interactor)	[UndirectedInteraction:11164937] UniProt:P63279 <-> UniProt:O75928 (IntAct) [UndirectedInteraction:11183723] UniProt:P63165 <-> UniProt:O75928 (IntAct) [UndirectedInteraction:11191309] UniProt:O96006 <-> UniProt:O75928 (IntAct) [UndirectedInteraction:11198317] UniProt:Q08379 <-> UniProt:O75928 (IntAct) [UndirectedInteraction:11200489] UniProt:P04637 <-> UniProt:O75928 (IntAct) [UndirectedInteraction:11208371] UniProt:P01106 <-> UniProt:O75928 (IntAct) [UndirectedInteraction:11269839] UniProt:P14136 <-> UniProt:O75928 (IntAct) [UndirectedInteraction:11278031] UniProt:O75928 <-> UniProt:Q8IVL1 (IntAct) [UndirectedInteraction:11278033] UniProt:O75928 <-> UniProt:O95273 (IntAct) [UndirectedInteraction:11278035] UniProt:O75928 <-> UniProt:Q96T51 (IntAct) [UndirectedInteraction:11278037] UniProt:O75928 <-> UniProt:Q96HD9 (IntAct) [UndirectedInteraction:11278039] UniProt:O75928 <-> UniProt:Q96BR9 (IntAct) [UndirectedInteraction:11278041] UniProt:O75928 <-> UniProt:O43741 (IntAct) [UndirectedInteraction:11278043] UniProt:O75928 <-> UniProt:P20592 (IntAct) [UndirectedInteraction:11278045] UniProt:O75928 <-> UniProt:Q7KZS0 (IntAct) [UndirectedInteraction:11278047] UniProt:O75928 <-> UniProt:Q969E8 (IntAct) [UndirectedInteraction:11278049] UniProt:O75928 <-> UniProt:Q59GP6 (IntAct) [UndirectedInteraction:11278051] UniProt:O75928 <-> UniProt:G2XKQ0 (IntAct) [UndirectedInteraction:11278053] UniProt:O75928 <-> UniProt:Q8TD31-3 (IntAct) [UndirectedInteraction:11278055] UniProt:O75928 <-> UniProt:P36406 (IntAct) [UndirectedInteraction:11278057] UniProt:O75928 <-> UniProt:P0C206 (IntAct)