protein
Brefeldin A-inhibited guanine nucleotide-exchange protein 3
Gene
ARFGEF3
Organism
Homo sapiens(9606)
Length
2177 aa
Mass
240,652 Da
ARFGEF3 (Brefeldin A-inhibited guanine nucleotide-exchange protein 3) is a large guanine nucleotide-exchange factor that regulates insulin and glucagon granule biogenesis in pancreatic beta and alpha cells, respectively (UniProt: Q5TH69). The protein also modulates nuclear translocation of PHB2 and may influence estrogen receptor alpha transcriptional activity in breast cancer cells. It is a 2177-amino acid protein with a molecular mass of approximately 240.7 kDa.
ARFGEF3 is primarily associated with glucose homeostasis and pancreatic endocrine function. UniProt records no primary disease associations, though its role in systemic metabolic regulation suggests potential relevance to metabolic disorders.
In Alzheimer's disease, ARFGEF3 is downregulated in post-mortem human AD brain tissue compared to age-matched controls (mean log2FC: −0.417) as detected by TMT-labeled quantitative proteomics across four subcellular fractions (Chaparral AD proteomics). The functional significance of this downregulation in the context of AD neurodegeneration remains to be determined.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.417
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.417 (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
Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (By similarity). Also regulates glucagon granule production in pancreatic alpha cells (By similarity). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (PubMed:19496786)
Sources
Last updated 5/8/2026, 6:30:48 AM