protein
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2
aka AGAP-2
Gene
AGAP2
Organism
Homo sapiens(9606)
Length
1192 aa
Mass
124,591 Da
AGAP2 encodes Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2, a GTPase-activating protein that regulates ARF1 and ARF5 activity. Multiple isoforms possess distinct functions: isoform 1 prevents neuronal apoptosis by enhancing PI3 kinase activity through coupling of metabotropic glutamate receptor 1 to cytoplasmic PI3 kinase via Homer scaffolding proteins, while isoform 2 stimulates Akt-mediated cytoprotection and regulates AP-1-dependent endosomal trafficking (UniProt: Q99490).
AGAP2 is broadly expressed with roles in neuroprotection and vesicular trafficking. The protein has been noted in cancer biology for its anti-apoptotic and invasive properties, though no primary disease associations are documented in UniProt.
In Alzheimer's Disease, AGAP2 is significantly downregulated in post-mortem AD brain compared to age-matched controls (mean log2FC: −0.70; Chaparral AD proteomics). This reduction was observed across 2 of 4 subcellular fractions in a TMT-labeled proteomic study, suggesting potential loss of PI3 kinase-mediated neuroprotection in AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.725
P2
not detected
S2
-0.683
S3
not detected
Mean log₂FC across detected fractions: -0.7038 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
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
Sources
Last updated 5/8/2026, 6:36:13 AM