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PIKE

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

  • AGAP-2
  • Centaurin-gamma-1
  • GTP-binding and GTPase-activating protein 2
  • Phosphatidylinositol 3-kinase enhancer
  • Cnt-g1
  • GGAP2
  • PIKE
  • AGAP2
  • CENTG1
  • KIAA0167

Target type

Proteins

Molecular weight

124674Da