PIAS3

This gene encodes a member of the PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] family of transcriptional modulators. The protein functions as a SUMO (small ubiquitin-like modifier)-E3 ligase which catalyzes the covalent attachment of a SUMO protein to specific target substrates. It directly binds to several transcription factors and either blocks or enhances their activity. Alternatively spliced transcript variants of this gene have been identified, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

Full Name

Protein Inhibitor Of Activated STAT 3

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 coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (PubMed:21965678, PubMed:9388184).
Sumoylates CCAR2 which promotes its interaction with SIRT1 (PubMed:25406032).
Diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus (PubMed:24651376).

Biological Process

Negative regulation of gene expressionIEA:Ensembl
Negative regulation of osteoclast differentiationIEA:Ensembl
Negative regulation of protein sumoylationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Positive regulation of gene expressionIEA:Ensembl
Positive regulation of membrane potentialIEA:Ensembl
Positive regulation of protein sumoylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein sumoylationISS:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Response to hormoneIEA:Ensembl
TNFSF11-mediated signaling pathwayIEA:Ensembl

Cellular Location

Cytoplasm
Nucleus
Nucleus speckle
Colocalizes with MITF in the nucleus. Colocalizes with GFI1 in nuclear dots. Colocalizes with SUMO1 in nuclear granules.

PTM

Sumoylated.