ARF1

Function

Small GTPase involved in protein trafficking between different compartments (PubMed:8253837). Modulates vesicle budding and uncoating within the Golgi complex (PubMed:8253837). In its GTP-bound form, triggers the recruitment of coatomer proteins to the Golgi membrane (PubMed:8253837). The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles (PubMed:8253837). The GTP-bound form interacts with PICK1 to limit PICK1-mediated inhibition of Arp2/3 complex activity; the function is linked to AMPA receptor (AMPAR) trafficking, regulation of synaptic plasticity of excitatory synapses and spine shrinkage during long-term depression (LTD) (By similarity). Plays a key role in the regulation of intestinal stem cells and gut microbiota, and is essential for maintaining intestinal homeostasis (By similarity). Plays also a critical role in mast cell expansion but not in mast cell maturation by facilitating optimal mTORC1 activation (By similarity).

(Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.

Involvement in disease

Periventricular nodular heterotopia 8

PVNH8

A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH8 is an autosomal dominant disease characterized by developmental disabilities, speech delay, seizures and attention deficit-hyperactivity disorder.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

(Microbial infection) Demyristoylated by S.flexneri cysteine protease IpaJ which cleaves the peptide bond between N-myristoylated Gly-2 and Asn-3.

Sequence Similarities

Belongs to the small GTPase superfamily. Arf family.

Cellular localization

• Golgi apparatus membrane
• Lipid-anchor
• Cytoplasmic side
• Synapse
• Synaptosome
• Postsynaptic density
• In the GDP-bound form, associates transiently with the membranes via its myristoylated N-terminus where guanine nucleotide-exchange factor (GEF)-mediated nucleotide exchange occurs (By similarity). Following nucleotide exchange, the GTP-bound form undergoes a conformational change, leading to the exposure of a myristoylated N-terminal amphipathic helix that provides stable membrane anchorage (By similarity).

Alternative names

ADP-ribosylation factor 1, ARF1

Database links

swissprot:P84077 entrezGene:375 swissprot:P61204 omim:103180 omim:103190 entrezGene:377