Agap2 ArfGAP with GTPase domain, ankyrin repeat and PH domain 2
ANK repeat and PH domains 2
Arf GAP with GTP binding protein like
Arf GAP with GTP-binding protein-like, ANK repeat and PH domains 2
Arf GAP with GTP-binding protein-like, ankyrin repeat and pleckstrin homology domains 2
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2
ArfGAP with GTPase domain, ankyrin repeat and PH domain 2
GTP binding and GTPase activating protein 2
GTP-binding and GTPase activating protein 2
GTP-binding and GTPase-activating protein 2
Nuclear GTPase PIKE
Phosphatidylinositol 3-kinase enhancer
Phosphoinositide 3 kinase enhancer
FunctionGTPase-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.
Tissue specificityIsoform 1 is brain-specific. Isoform 2 is ubiquitously expressed, with highest levels in brain and heart.
Sequence similaritiesBelongs to the centaurin gamma-like family. Contains 2 ANK repeats. Contains 1 Arf-GAP domain. Contains 1 PH domain.
DomainG 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.
Post-translational modificationsIsoform PIKE-A is phosphorylated at Tyr-682 and Tyr-774 by FYN, preventing its apoptotic cleavage.
Cellular localizationCytoplasm and Cytoplasm. Nucleus.