VAMP1

Synapotobrevins, syntaxins, and the synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Mutations in this gene are associated with autosomal dominant spastic ataxia 1. Multiple alternative splice variants have been described, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2014]

Full Name

Vesicle Associated Membrane Protein 1

Function

Involved in the targeting and/or fusion of transport vesicles to their target membrane.

Biological Process

Biological Process SNARE complex assembly Source:GO_Central1 Publication
Biological Process vesicle fusion Source:GO_Central1 Publication

Cellular Location

Isoform 1
Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane
Synapse, synaptosome
Isoform 2
Cytoplasmic vesicle membrane
Synapse, synaptosome
Isoform 3
Mitochondrion outer membrane

Involvement in disease

Spastic ataxia 1, autosomal dominant (SPAX1):
An autosomal dominant form of spastic ataxia, a progressive neurodegenerative disorder characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance.
Myasthenic syndrome, congenital, 25, presynaptic (CMS25):
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS25 is an autosomal recessive form characterized by hypotonia and generalized muscle weakness apparent from birth. Affected individuals have feeding difficulties and delayed motor development, usually never achieving independent ambulation. Additional variable features include eye movement abnormalities, joint contractures, and rigid spine.

Topology

Cytoplasmic: 1-96
Helical: 97-116
Vesicular: 117-118

PTM

(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type B (BoNT/B, botB) which probably hydrolyzes the 78-Gln-|-Phe-79 bond and inhibits neurotransmitter release (PubMed:22289120).
(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type D (BoNT/D, botD) which probably hydrolyzes the 61-Arg-|-Leu-62 bond and inhibits neurotransmitter release (PubMed:22289120).
BoNT/D has low catalytic activity on this protein due to its sequence (PubMed:22289120).
Note that humans are not known to be infected by C.botulinum type D.
(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type F (BoNT/F, botF) which probably hydrolyzes the 60-Gln-|-Lys-61 bond and inhibits neurotransmitter release (PubMed:22289120).
(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type X (BoNT/X) which probably hydrolyzes the 68-Arg-|-Ala-69 bond and inhibits neurotransmitter release (PubMed:29540745).
It remains unknown whether BoNT/X is ever produced, or what organisms it targets.