SIPA1 (Signal-Induced Proliferation-Associated 1)
A Rap1 GTPase-Activating Protein Involved in Cell Adhesion, Migration, and Cancer Metastasis
Gene Information Card
| Symbol | SIPA1 |
|---|---|
| Full Name | Signal-Induced Proliferation-Associated 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 6494 ncbi.nlm.nih.gov/gene/6494 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q96FS4 |
| OMIM ID | 602242 |
| HGNC ID | 10885 |
| Aliases | SIPA1, Rap1GAP, SPA1 |
Description
SIPA1 (Signal-Induced Proliferation-Associated 1) encodes a GTPase-activating protein (GAP) that specifically inactivates Rap1 and Rap2 small GTPases by stimulating their intrinsic GTPase activity. Through Rap1 regulation, SIPA1 modulates integrin-mediated cell adhesion, cell spreading, and migration. The gene is implicated in cancer metastasis, particularly in breast and lung cancers, where altered expression or mutations influence tumor progression and patient outcome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | SIPA1 overexpression or gain-of-function variants enhance Rap1 inactivation, promoting cell migration and metastasis. | PMID: 15604239, COSMIC |
| Lung Cancer (non-small cell) | SIPA1 polymorphisms (e.g., rs931127) associated with increased risk of metastasis and poor prognosis. | PMID: 17999357, ClinVar |
| Colorectal Cancer | SIPA1 upregulation correlates with lymph node metastasis and advanced stage. | PMID: 20628036 |
| Prostate Cancer | SIPA1 expression linked to aggressive disease and biochemical recurrence. | PMID: 21804532 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lung | 8.2 | Medium |
| Breast | 6.1 | Low |
| Colon | 5.4 | Low |
| Prostate | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 14.2 | High expression; associated with invasive phenotype |
| A549 (lung cancer) | 11.5 | Moderate expression; linked to metastatic potential |
| HCT116 (colorectal cancer) | 9.8 | Moderate expression |
| PC3 (prostate cancer) | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.205G>A (p.Glu69Lys) | Missense | <1% | Altered GAP activity; potential gain-of-function |
| c.497C>T (p.Thr166Met) | Missense | <1% | Reduced Rap1 binding; loss-of-function |
| c.1123A>G (p.Ile375Val) | Missense | <1% | Unknown functional effect |
| rs931127 (intronic) | SNP | ~15% (population) | Associated with increased metastasis risk in lung cancer |
Mutation functional classification
Loss of Function (LOF)
p.Thr166Met reduces Rap1 binding and GAP activity, impairing Rap1 inactivation.
Gain of Function (GOF)
p.Glu69Lys enhances GAP activity, leading to excessive Rap1 inactivation and increased cell migration.
Dominant Negative (DN)
No dominant-negative mutations currently reported in SIPA1.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity (GO:0005096) | • Rap GTPase binding (GO:0017137) |
| • Rap1 GTPase activator activity (GO:0005097) | • Cell adhesion (GO:0007155) |
| • Cell migration (GO:0016477) | • Regulation of cell proliferation (GO:0042127) |
| • Cytoplasm (GO:0005737) | • Plasma membrane (GO:0005886) |
Pathways
• Rap1 signaling pathway (KEGG: hsa04015)
• Integrin-mediated cell adhesion (Reactome: R-HSA-446353)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
Protein Summary
SIPA1 is a 1042-amino-acid protein containing a Rap-GAP domain, a PDZ domain, and a C-terminal coiled-coil region. It localizes to the cytoplasm and plasma membrane, where it negatively regulates Rap1 and Rap2 signaling. By inactivating Rap1, SIPA1 controls integrin activation, cell adhesion dynamics, and migration. Aberrant SIPA1 function contributes to cancer metastasis, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIPA1L1 Knockout HEK293 Cell Line | EDJ-KQ1320 | Human | 26037 | Details Get a Quote |
| SIPA1 Knockout HEK293 Cell Line | EDJ-KQ1322 | Human | 6494 | Details Get a Quote |
| SIPA1L2 Knockout HEK293 Cell Line | EDJ-KQ1323 | Human | 57568 | Details Get a Quote |
| SIPA1L3 Knockout HEK293 Cell Line | EDJ-KQ1324 | Human | 23094 | Details Get a Quote |
| SIPA1 Knockout A-549 Cell Line | EDJ-KQ19412 | Human | 6494 | Details Get a Quote |
| SIPA1L3 Knockout HCT 116 Cell Line | EDJ-KQ19419 | Human | 23094 | Details Get a Quote |
| SIPA1L1 Knockout A-549 Cell Line | EDJ-KQ20755 | Human | 26037 | Details Get a Quote |
| SIPA1L1 Knockout HCT 116 Cell Line | EDJ-KQ20756 | Human | 26037 | Details Get a Quote |
| SIPA1L1 Knockout HeLa Cell Line | EDJ-KQ20757 | Human | 26037 | Details Get a Quote |
| SIPA1 Knockout HCT 116 Cell Line | EDJ-KQ20758 | Human | 6494 | Details Get a Quote |
| SIPA1 Knockout HeLa Cell Line | EDJ-KQ20759 | Human | 6494 | Details Get a Quote |
| SIPA1L2 Knockout A-549 Cell Line | EDJ-KQ20760 | Human | 57568 | Details Get a Quote |
| SIPA1L2 Knockout HCT 116 Cell Line | EDJ-KQ20761 | Human | 57568 | Details Get a Quote |
| SIPA1L2 Knockout HeLa Cell Line | EDJ-KQ20762 | Human | 57568 | Details Get a Quote |
| SIPA1L3 Knockout A-549 Cell Line | EDJ-KQ20763 | Human | 23094 | Details Get a Quote |
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