AGAP2
Domain
G domain binds GTP and has GTPase activity.
Arf-GAP domain interacts with G domain and may regulate its GTPase activity.
Although both PH domains of isoforms 1 and 2 bind phospholipids, they differently regulate subcellular location. PH domain of isoform 1 directs the protein to the nucleus, but PH domain of isoform 2 directs it to the cytosol. PH domain of isoform 2 is required for binding to AP-1.
Function
GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion.
Post-translational modifications
Isoform PIKE-A is phosphorylated at Tyr-682 and Tyr-774 by FYN, preventing its apoptotic cleavage.
Sequence Similarities
Belongs to the centaurin gamma-like family.
Tissue Specificity
Isoform 1 is brain-specific. Isoform 2 is ubiquitously expressed, with highest levels in brain and heart.
Cellular localization
- Isoform 1
- Cytoplasm
- Nucleus
- Isoform 2
- Cytoplasm
Alternative names
CENTG1, KIAA0167, AGAP2, AGAP-2, Centaurin-gamma-1, GTP-binding and GTPase-activating protein 2, Phosphatidylinositol 3-kinase enhancer, Cnt-g1, GGAP2, PIKE