ARFGEF2
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.
Involvement in disease
Periventricular nodular heterotopia 2
PVNH2
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1.
Tissue Specificity
Expressed in placenta, lung, heart, brain, kidney and pancreas.
Cellular localization
- Cytoplasm
- Membrane
- Golgi apparatus
- Cytoplasm
- Perinuclear region
- Golgi apparatus
- trans-Golgi network
- Endosome
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cell projection
- Dendrite
- Cytoplasmic vesicle
- Synapse
- Cytoplasm
- Cytoskeleton
- Translocates from cytoplasm to membranes upon cAMP treatment. Localized in recycling endosomes.
Alternative names
ARFGEP2, BIG2, ARFGEF2, Brefeldin A-inhibited guanine nucleotide-exchange protein 2, Brefeldin A-inhibited GEP 2, ADP-ribosylation factor guanine nucleotide-exchange factor 2