E3 SUMO-protein ligase PIAS4/PIASy

Domain

The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.

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, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation.

Pathway

Protein modification; protein sumoylation.

Post-translational modifications

Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate.

Sequence similarities

Belongs to the PIAS family.

Tissue specificity

Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes.

Cellular localization

• Nucleus
• PML body
• Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies.

Alternative names

• E3 SUMO-protein ligase PIAS4
• PIASy
• Protein inhibitor of activated STAT protein 4
• Protein inhibitor of activated STAT protein gamma
• RING-type E3 ubiquitin transferase PIAS4
• PIAS-gamma
• PIAS4
• PIASG

Database links

• entrezGene:51588
• omim:605989
• swissprot:Q8N2W9

Target type

Proteins

Primary research area

Epigenetics

Molecular weight

56504Da