VAPB
Domain
The MSP domain binds the FFAT motif of many proteins.
Function
Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMed:32344433, PubMed:33124732). Interacts with STARD3 in a FFAT motif phosphorylation dependent manner (PubMed:33124732). Via interaction with WDR44 participates in neosynthesized protein export (PubMed:32344433). Participates in the endoplasmic reticulum unfolded protein response (UPR) by inducing ERN1/IRE1 activity (PubMed:16891305, PubMed:20940299). Involved in cellular calcium homeostasis regulation (PubMed:22131369).
Involvement in disease
Amyotrophic lateral sclerosis 8
ALS8
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
None
The disease is caused by variants affecting the gene represented in this entry.
Spinal muscular atrophy, proximal, adult, autosomal dominant
SMAPAD
A form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAPAD is characterized by proximal muscle weakness that begins in the lower limbs and then progresses to upper limbs, onset in late adulthood (after third decade) and a benign course. Most of the patients remain ambulatory 10 to 40 years after clinical onset.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family.
Tissue Specificity
Ubiquitous. Isoform 1 predominates.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass type IV membrane protein
- Present in mitochondria-associated membranes that are endoplasmic reticulum membrane regions closely apposed to the outer mitochondrial membrane.
Alternative names
UNQ484/PRO983, VAPB, Vesicle-associated membrane protein-associated protein B/C, VAMP-B/VAMP-C, VAMP-associated protein B/C, VAP-B/VAP-C