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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)
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
Structure:
- 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
Compartment:
- isoform 1: cytoplasm. nucleus
- isoform 2: cytoplasm
Alternative splicing: named isoforms=2
Expression:
- isoform 1 is brain-specific
- isoform 2 is ubiquitously expressed with highest levels in brain & heart
Related
pleckstrin homology [PH] domain
pleckstrin; platelet p47 protein (PLEK P47)
General
ankyrin repeat domain protein (ANKRD)
centaurin gamma
phosphoprotein
Properties
SIZE: entity length = 1192 aa
MW = 125 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: EPB41L1 interaction {1-23}
Ser phosphorylation site {S149}
HOMER1/NF2 interaction {180-225}
PLCG1 interaction {267-390}
MOTIF: Ser phosphorylation site {S267}
G {405-572}
MOTIF: GTP-binding site
SITE: 413-420
GTP-binding site
SITE: 457-461
GTP-binding site
SITE: 515-518
Thr phosphorylation site {T635}
Ser phosphorylation site {S638}
PH domain {676-910}
MOTIF: Ser phosphorylation site {S808}
Ser phosphorylation site {S865}
Ser phosphorylation site {S927}
Arf-GAP domain
NAME: Arf-GAP domain
SITE: 931-1051
MOTIF: Zn finger C4-type
SITE: 946-969
EFFECTOR-BOUND: Zn+2
ankyrin repeat
NAME: ankyrin repeat
SITE: 1090-1119
ankyrin repeat
NAME: ankyrin repeat
SITE: 1123-1152
Database Correlations
OMIM 605476
UniProt Q99490
PFAM correlations
Entrez Gene 116986
Kegg hsa:116986
References
- UniProt :accession Q99490
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/CENTG1ID44037ch12q14.html