centaurin-gamma-1; Arf-GAP with GTPase, ANK repeat & PH domain-containing protein 2; AGAP-2; Cnt-g1; GTP-binding & GTPase-activating protein 2; GGAP2; phosphatidylinositol-3-kinase enhancer; PIKE (AGAP2, CENTG1, KIAA0167)

^[1]^[2]

Function

GTPase-activating protein (GAP) for ARF1 & ARF5, which also shows strong GTPase activity
isoform 1:
- participates in prevention of neuronal apoptosis by enhancing PI3 kinase activity
- aids coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with homer scaffolding proteins
- seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase
isoform 2:
- does not stimulate PI3 kinase
- may protect cells from apoptosis by stimulating Akt
- regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system
- seems to be oncogenic
- overexpressed in cancer cells, prevents apoptosis & promotes cancer cell invasion
GAP activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) &, to a lesser extent, by phosphatidylinositol 3,4,5-trisphosphate (PIP3)
phosphatidic acid potentiates PIP2 stimulation
isoform 1 interacts with EPB41L1, PLCG1, NF2, HOMER1 & HOMER2 (putative)
isoform 2 interacts with activated AKT1 in the presence of guanine nucleotides, & with the AP-1 complex

G domain binds GTP & has GTPase activity
Arf-GAP domain interacts with G domain & may regulate its GTPase activity
although both PH domains of isoforms 1 & 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
belongs to the centaurin gamma-like family
contains 2 ANK repeats
contains 1 Arf-GAP domain
contains 1 PH domain