PIAS4

PIAS4 has broad expression in testis (RPKM 14.8), spleen (RPKM 3.8) and 25 other tissues.

Full Name

Protein Inhibitor Of Activated STAT 4

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 (PubMed:12511558, PubMed:12631292, PubMed:12727872, PubMed:15831457, PubMed:15976810, PubMed:22508508, PubMed:32832608).
Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168 (PubMed:12511558, PubMed:12631292, PubMed:12727872, PubMed:15831457, PubMed:15976810, PubMed:22508508).
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 (PubMed:11388671).
Involved in gene silencing (PubMed:11248056).
In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations (PubMed:12727872, PubMed:15831457).
Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (PubMed:21965678).
Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (By similarity).
Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:32832608).

Biological Process

Central nervous system developmentIEA:Ensembl
Double-strand break repairTAS:Reactome
Hair follicle developmentIEA:Ensembl
Limb epidermis developmentIEA:Ensembl
Negative regulation of NF-kappaB transcription factor activityIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of tumor necrosis factor-mediated signaling pathwayIEA:Ensembl
Positive regulation of double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of intrinsic apoptotic signaling pathway in response to DNA damageIEA:Ensembl
Positive regulation of keratinocyte apoptotic processISS:BHF-UCL
Positive regulation of protein sumoylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein sumoylationManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Vitamin D metabolic processTAS:Reactome
Wnt signaling pathwayIEA:UniProtKB-KW

Cellular Location

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

PTM

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.