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MGP006374

UniProt Annotations

Entry Information

Gene Name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 2
Protein Entry	AGAP2_HUMAN
UniProt ID	Q99490
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=PIKE-L; IsoId=Q99490-1; Sequence=Displayed; Name=2; Synonyms=PIKE-A; IsoId=Q99490-2; Sequence=VSP_018531, VSP_018532, VSP_018533; Note=Contains a phosphotyrosine at position 682. Contains a phosphotyrosine at position 774.;
Domain	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.
Domain	Arf-GAP domain interacts with G domain and may regulate its GTPase activity.
Domain	G domain binds GTP and has GTPase activity.
Enzyme Regulation	GAP activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and, to a lesser extent, by phosphatidylinositol 3,4,5-trisphosphate (PIP3). Phosphatidic acid potentiates PIP2 stimulation.
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. {ECO:0000269\|PubMed:12640130, ECO:0000269\|PubMed:14761976, ECO:0000269\|PubMed:15118108, ECO:0000269\|PubMed:16079295}.
Interaction	P06213:INSR; NbExp=2; IntAct=EBI-2361824, EBI-475899; Q08501:Prlr (xeno); NbExp=2; IntAct=EBI-7737644, EBI-7737664; P42229:STAT5A; NbExp=3; IntAct=EBI-7737644, EBI-749537; P42230:Stat5a (xeno); NbExp=2; IntAct=EBI-7737644, EBI-617434;
Ptm	Isoform PIKE-A is phosphorylated at Tyr-682 and Tyr-774 by FYN, preventing its apoptotic cleavage. {ECO:0000269\|PubMed:19690332}.
Sequence Caution	Sequence=BAA11484.2; Type=Erroneous initiation; Evidence={ECO:0000305};
Similarity	Belongs to the centaurin gamma-like family. {ECO:0000305}.
Similarity	Contains 1 Arf-GAP domain. {ECO:0000255\|PROSITE- ProRule:PRU00288}.
Similarity	Contains 1 PH domain. {ECO:0000255\|PROSITE- ProRule:PRU00145}.
Similarity	Contains 2 ANK repeats. {ECO:0000255\|PROSITE- ProRule:PRU00023}.
Subcellular Location	Isoform 1: Cytoplasm. Nucleus.
Subcellular Location	Isoform 2: Cytoplasm.
Subunit	Isoform 1 interacts with EPB41L1, PLCG1, NF2, HOMER1 and HOMER2 (By similarity). Isoform 2 interacts with activated AKT1 in the presence of guanine nucleotides, and with the AP-1 complex. {ECO:0000250, ECO:0000269\|PubMed:14761976, ECO:0000269\|PubMed:15118108, ECO:0000269\|PubMed:16079295}.
Tissue Specificity	Isoform 1 is brain-specific. Isoform 2 is ubiquitously expressed, with highest levels in brain and heart. {ECO:0000269\|PubMed:12640130, ECO:0000269\|PubMed:14761976, ECO:0000269\|PubMed:15118108, ECO:0000269\|PubMed:16079295, ECO:0000269\|PubMed:16150119}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CENTG1ID44037ch12q14.html";