PIAS4 Gene - Protein Inhibitor of Activated STAT 4
A key regulator of SUMOylation and transcriptional activity in cancer and immune signaling
Gene Information Card
| Symbol | PIAS4 |
|---|---|
| Full Name | Protein Inhibitor of Activated STAT 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 51588 ncbi.nlm.nih.gov/gene/51588 |
| Ensembl ID | ENSG00000105229 |
| UniProt ID | Q8N2W9 |
| OMIM ID | 605989 |
| HGNC ID | 17002 |
| Aliases | PIASG, ZMIZ4, MGC12529 |
Description
PIAS4 (Protein Inhibitor of Activated STAT 4) encodes a member of the PIAS family of SUMO E3 ligases. The protein modulates transcriptional activity by SUMOylating target transcription factors, including STAT1, p53, and NF-κB, thereby influencing cell growth, apoptosis, and immune responses. PIAS4 is involved in DNA repair, chromatin remodeling, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | PIAS4 overexpression promotes SUMOylation of p53, reducing its tumor suppressor activity | PMID: 21502514 |
| Prostate Cancer | PIAS4 enhances androgen receptor SUMOylation, contributing to hormone resistance | PMID: 23103858 |
| Colorectal Cancer | PIAS4 upregulation correlates with poor prognosis and increased Wnt/β-catenin signaling | PMID: 27626308 |
| Inflammatory Diseases | PIAS4 modulates NF-κB SUMOylation, affecting cytokine production | PMID: 19029902 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Lymph node | 12.8 | Medium |
| Bone marrow | 11.5 | Medium |
| Brain | 6.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.5 | High expression |
| HeLa | 14.2 | Moderate expression |
| MCF7 | 12.0 | Moderate expression |
| K562 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | <0.1% | Alters SUMO ligase activity |
| c.1021G>A (p.Glu341Lys) | Missense | <0.1% | Unknown functional impact |
| c.1345_1346insA | Frameshift | <0.1% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.1345_1346insA) are predicted to truncate the protein and abolish SUMO E3 ligase activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in major databases.
Dominant Negative (DN)
Missense variants in the RING finger domain may act as dominant-negative by competing with wild-type PIAS4 for substrate binding.
View complete mutation data：
Gene Ontology (GO)
| • SUMO transferase activity (GO:0019789) | • protein SUMOylation (GO:0016925) |
| • transcription coregulator activity (GO:0003712) | • nucleus (GO:0005634) |
| • DNA repair (GO:0006281) |
Pathways
• SUMOylation (Reactome R-HSA-2990846)
• p53 signaling (KEGG hsa04115)
• NF-κB signaling (KEGG hsa04064)
• Wnt signaling (KEGG hsa04310)
Protein Summary
PIAS4 is a 510-amino acid protein containing a SAP domain, a RING-type zinc finger, and a SUMO-interacting motif. It functions as a SUMO E3 ligase, facilitating the attachment of SUMO proteins to specific substrates. PIAS4 regulates transcription factors such as p53, STAT1, and NF-κB, impacting cell cycle, apoptosis, and immune responses. Its expression is elevated in several cancers and immune tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIAS4 Knockout HEK293 Cell Line | EDJ-KQ143 | Human | 51588 | Details Get a Quote |
| PIAS4 Knockout A-549 Cell Line | EDJ-KQ18994 | Human | 51588 | Details Get a Quote |
| PIAS4 Knockout HCT 116 Cell Line | EDJ-KQ18995 | Human | 51588 | Details Get a Quote |
| PIAS4 Knockout HeLa Cell Line | EDJ-KQ18996 | Human | 51588 | Details Get a Quote |
