protein
Brefeldin A-inhibited guanine nucleotide-exchange protein 2
aka Brefeldin A-inhibited GEP 2
Gene
ARFGEF2
Organism
Homo sapiens(9606)
Length
1785 aa
Mass
202,038 Da
ARFGEF2 (Brefeldin A-inhibited guanine nucleotide-exchange protein 2) is a guanine nucleotide-exchange factor that activates ARF GTPases (ARF1, ARF3, ARF5, and ARF6) by promoting GDP-to-GTP exchange (UniProt: Q9Y6D5). The protein regulates Golgi and endosomal membrane trafficking, including trans-Golgi network to endosome transport, AP-1 complex recruitment, transferrin receptor recycling, and GABA(A) receptor exit from the endoplasmic reticulum. It may also function as an A kinase-anchoring protein linking ARF and PKA signaling pathways (UniProt: Q9Y6D5).
ARFGEF2 is associated with periventricular nodular heterotopia 2 (PVNH2), a recessive developmental disorder affecting neuronal migration and characterized by microcephaly and severe developmental delay (UniProt: Q9Y6D5). The protein's role in membrane trafficking and receptor trafficking suggests broader relevance to neuronal homeostasis.
In Alzheimer's disease, ARFGEF2 is significantly downregulated in human post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.28) (Chaparral AD proteomics). This downregulation may impair vesicular transport and endosomal function, processes implicated in amyloid precursor protein processing and AD pathogenesis.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.276
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.2758 (1 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
Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways
Disease associations
Periventricular nodular heterotopia 2PVNH2
A developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH2 is an autosomal recessive form characterized by microcephaly (small brain), severe developmental delay and recurrent infections. No anomalies extrinsic to the central nervous system, such as dysmorphic features or grossly abnormal endocrine or other conditions, are associated with PVNH2.
Sources
Last updated 5/8/2026, 6:30:45 AM