GIT2 Gene - ARF GTPase-Activating Protein
GIT2: A Multifunctional Scaffold Protein in Cell Signaling and Cancer
Gene Information Card
| Symbol | GIT2 |
|---|---|
| Full Name | GIT ArfGAP 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 9815 ncbi.nlm.nih.gov/gene/9815 |
| Ensembl ID | ENSG00000139436 |
| UniProt ID | Q14161 |
| OMIM ID | 608564 |
| HGNC ID | 4272 |
| Aliases | CAT-2, GIT2L, KIAA0148, ARF1GAP2, GIT2-201 |
Description
GIT2 (GIT ArfGAP 2) encodes a member of the GIT family of GTPase-activating proteins (GAPs) that regulate ARF small GTPases. The protein functions as a scaffold in multiple signaling complexes, including those involved in cell adhesion, migration, and receptor internalization. GIT2 interacts with paxillin, PIX, and PAK to coordinate cytoskeletal dynamics and focal adhesion turnover. Alternative splicing generates multiple isoforms with distinct functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | GIT2 overexpression correlates with poor prognosis; promotes cell migration via ARF6 inactivation | PMID: 25609832 |
| Colorectal cancer | GIT2 silencing reduces tumor growth and metastasis in xenograft models | PMID: 27323851 |
| Hepatocellular carcinoma | GIT2 upregulation associated with EMT and invasion | PMID: 30356098 |
| Melanoma | GIT2 loss enhances ARF6 activity and metastatic potential | PMID: 21880731 |
| Intellectual disability | De novo GIT2 missense variants identified in neurodevelopmental disorder | ClinVar: RCV001851378 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.8 | Medium |
| Spleen | 7.4 | Low |
| Colon | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney; high expression |
| HeLa | 11.5 | Cervical carcinoma; moderate |
| A549 | 8.9 | Lung carcinoma; moderate |
| MCF7 | 6.3 | Breast carcinoma; low |
| HepG2 | 5.1 | Hepatocellular carcinoma; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | 0.001% (gnomAD) | Loss of GAP activity; associated with intellectual disability |
| c.1670A>G (p.Tyr557Cys) | Missense | 0.0005% | Reduced paxillin binding; altered cell migration |
| c.2146_2148del (p.Lys716del) | In-frame deletion | 0.002% | Impaired focal adhesion turnover |
| c.289C>T (p.Arg97*) | Nonsense | <0.0001% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay; missense variants impairing GAP activity or scaffold interactions.
Gain of Function (GOF)
Not well documented; some missense variants may enhance ARF6 binding but functional data are limited.
Dominant Negative (DN)
Missense mutations that disrupt paxillin or PIX binding without complete loss of protein may act as dominant negatives in focal adhesion signaling.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • ARF GTPase activator activity |
| • protein binding | • focal adhesion |
| • cytosol | • cell leading edge |
| • signal transduction | • regulation of cell migration |
| • regulation of ARF protein signal transduction |
Pathways
• ARF6 signaling pathway
• Focal adhesion
• Regulation of actin cytoskeleton
• PAK signaling
• GPCR signaling
Protein Summary
GIT2 is a 761-amino acid multidomain protein containing an N-terminal ARF-GAP domain, ankyrin repeats, a Spa2 homology domain, and a C-terminal paxillin-binding domain. It localizes to focal adhesions and the leading edge of migrating cells. GIT2 acts as a GTPase-activating protein for ARF1 and ARF6, inactivating them by promoting GTP hydrolysis. Through its scaffold function, it assembles signaling complexes with PIX, PAK, and paxillin to coordinate cytoskeletal remodeling, cell polarity, and migration. GIT2 also participates in clathrin-mediated endocytosis and receptor recycling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GIT2 Knockout HEK293 Cell Line | EDJ-KQ6764 | Human | 9815 | Details Get a Quote |
| GIT2 Knockout A-549 Cell Line | EDJ-KQ31201 | Human | 9815 | Details Get a Quote |
| GIT2 Knockout HCT 116 Cell Line | EDJ-KQ31202 | Human | 9815 | Details Get a Quote |
| GIT2 Knockout HeLa Cell Line | EDJ-KQ31203 | Human | 9815 | Details Get a Quote |
