PIAS3: Protein Inhibitor of Activated STAT3
A key regulator of STAT signaling and transcriptional activity
Gene Information Card
| Symbol | PIAS3 |
|---|---|
| Full Name | Protein Inhibitor of Activated STAT3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.1 |
| NCBI Gene ID | 10401 ncbi.nlm.nih.gov/gene/10401 |
| Ensembl ID | ENSG00000144857 |
| UniProt ID | Q9Y6X2 |
| OMIM ID | 605987 |
| HGNC ID | 16876 |
| Aliases | ZMIZ5, MGC14684 |
Description
PIAS3 (Protein Inhibitor of Activated STAT3) encodes a member of the PIAS family of transcriptional regulators. The protein functions as a SUMO E3 ligase and inhibits STAT3-mediated gene activation by blocking DNA binding and promoting sumoylation of transcription factors. PIAS3 is involved in cytokine signaling, cell growth, and immune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | PIAS3 overexpression suppresses STAT3 activity, reducing tumor growth | PMID: 15601830 |
| Prostate cancer | Loss of PIAS3 expression correlates with increased STAT3 activation and progression | PMID: 17909063 |
| Glioblastoma | PIAS3 downregulation enhances STAT3 signaling and tumor invasiveness | PMID: 19029908 |
| Inflammatory bowel disease | PIAS3 modulates STAT3-dependent inflammatory cytokine production | PMID: 21750552 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Lymph node | 9.8 | Medium |
| Bone marrow | 8.5 | Medium |
| Brain | 6.2 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | High expression |
| HeLa | 8.4 | Moderate expression |
| MCF7 | 7.2 | Moderate expression |
| K562 | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | 0.01% | Reduced SUMO ligase activity |
| c.1246G>A (p.Gly416Arg) | Missense | 0.005% | Altered protein stability |
| c.1570_1572del (p.Lys524del) | In-frame deletion | <0.001% | Impaired STAT3 binding |
Mutation functional classification
Loss of Function (LOF)
Mutations reducing SUMO ligase activity or STAT3 binding lead to loss of inhibitory function, promoting STAT3 hyperactivation.
Gain of Function (GOF)
Not well characterized; potential gain-of-function mutations may enhance STAT3 inhibition.
Dominant Negative (DN)
Truncating or deletion mutations that interfere with wild-type PIAS3 function have been proposed.
View complete mutation data：
Gene Ontology (GO)
| • transcription coregulator activity (GO:0003712) | • protein binding (GO:0005515) |
| • protein sumoylation (GO:0016925) | • nucleus (GO:0005634) |
| • JAK-STAT cascade (GO:0007259) |
Pathways
• JAK-STAT signaling pathway (KEGG: hsa04630)
• SUMOylation (Reactome: R-HSA-3108232)
• IL-6 signaling (Reactome: R-HSA-1059683)
Protein Summary
PIAS3 is a 628-amino acid protein containing a SAP domain, a PINIT domain, and a RING-type zinc finger. It acts as a SUMO E3 ligase, facilitating the attachment of SUMO to target proteins such as STAT3, p53, and NF-κB. Through sumoylation and direct binding, PIAS3 represses STAT3 transcriptional activity, thereby modulating cell proliferation, differentiation, and immune responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIAS3 Knockout HEK293 Cell Line | EDJ-KQ517 | Human | 10401 | Details Get a Quote |
| PIAS3 Knockout A-549 Cell Line | EDJ-KQ18847 | Human | 10401 | Details Get a Quote |
| PIAS3 Knockout HCT 116 Cell Line | EDJ-KQ18848 | Human | 10401 | Details Get a Quote |
| PIAS3 Knockout HeLa Cell Line | EDJ-KQ18849 | Human | 10401 | Details Get a Quote |
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