PIAS2: Protein Inhibitor of Activated STAT 2
A key regulator of SUMOylation and transcriptional activity in cancer and developmental disorders
Gene Information Card
| Symbol | PIAS2 |
|---|---|
| Full Name | Protein Inhibitor of Activated STAT 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q21.1 |
| NCBI Gene ID | 9063 ncbi.nlm.nih.gov/gene/9063 |
| Ensembl ID | ENSG00000101558 |
| UniProt ID | O75928 |
| OMIM ID | 603566 |
| HGNC ID | 17311 |
| Aliases | ARIP3, MIZ1, PIASX, ZMIZ4 |
Description
PIAS2 (Protein Inhibitor of Activated STAT 2) encodes a member of the PIAS family of SUMO E3 ligases. The protein regulates transcription by sumoylating transcription factors such as STAT1, STAT4, p53, and androgen receptor, modulating their activity, localization, and stability. PIAS2 is involved in immune response, cell cycle control, and development. Alternative splicing generates multiple isoforms with distinct functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | PIAS2 sumoylates androgen receptor, enhancing its transcriptional activity and promoting tumor growth | PMID: 11551966 |
| Breast cancer | PIAS2 overexpression correlates with poor prognosis; regulates estrogen receptor signaling | PMID: 20010870 |
| Colorectal cancer | PIAS2 mutations found in COSMIC; altered SUMOylation of β-catenin | COSMIC v99 |
| Developmental disorders | PIAS2 variants associated with intellectual disability and congenital anomalies | ClinVar RCV000169851.2 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.2 | Cervical cancer cell line |
| HEK293 | 7.8 | Embryonic kidney cells |
| MCF7 | 11.4 | Breast cancer cell line |
| HCT116 | 6.5 | Colorectal cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | 0.01% | ClinVar: uncertain significance; may affect SUMO ligase activity |
| c.1450G>A (p.Glu484Lys) | Missense | 0.005% | COSMIC: found in colorectal cancer |
| c.1687_1689del (p.Lys563del) | In-frame deletion | <0.001% | Reported in developmental delay |
Mutation functional classification
Loss of Function (LOF)
p.Arg375Trp may reduce SUMO E3 ligase activity, impairing transcriptional regulation.
Gain of Function (GOF)
Not well characterized; overexpression in cancers suggests potential gain-of-function via enhanced AR sumoylation.
Dominant Negative (DN)
p.Lys563del may interfere with wild-type PIAS2 function in SUMOylation complexes.
View complete mutation data：
Gene Ontology (GO)
| • GO:0016925 (GO:0016925) | • GO:0003712 (GO:0003712) |
| • GO:0005634 (GO:0005634) | • GO:0005515 (GO:0005515) |
| • GO:0042802 (GO:0042802) |
Pathways
• SUMOylation (Reactome: R-HSA-2990846)
• Transcriptional regulation by RUNX1 (Reactome: R-HSA-8878171)
• p53 pathway (KEGG: hsa04115)
Protein Summary
PIAS2 is a 572-amino acid protein containing a SAP domain, a PINIT domain, and a RING-type zinc finger essential for SUMO E3 ligase activity. It localizes to the nucleus and interacts with multiple transcription factors, including STATs, p53, and androgen receptor. PIAS2 modulates gene expression by promoting SUMO conjugation, leading to altered transcription factor activity, nuclear retention, or degradation. Isoforms vary in their C-terminal region, affecting substrate specificity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIAS2 Knockout HEK293 Cell Line | EDJ-KQ516 | Human | 9063 | Details Get a Quote |
| PIAS2 Knockout HCT 116 Cell Line | EDJ-KQ18014 | Human | 9063 | Details Get a Quote |
| PIAS2 Knockout A-549 Cell Line | EDJ-KQ18844 | Human | 9063 | Details Get a Quote |
| PIAS2 Knockout HeLa Cell Line | EDJ-KQ18846 | Human | 9063 | Details Get a Quote |
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