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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.
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