| 简介 | The protein encoded by this gene is a type IV membrane protein. It is present in the plasma membrane and intracellular vesicles. It may also be associated with the cytoskeleton. This protein may function in vesicle trafficking, membrane fusion, protein complex assembly and cell motility. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]
Diseases associated with VAPA include Amyotrophic Lateral Sclerosis 8 and Retinal Dystrophy With Leukodystrophy. Among its related pathways are Innate Immune System and Sphingolipid metabolism. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and structural molecule activity. An important paralog of this gene is VAPB.
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, 33124732).
STARD3-VAPA interaction enables cholesterol transfer from the ER to endosomes (PubMed:33124732).
Via interaction with WDR44 participates in neosynthesized protein export (PubMed:32344433).
In addition, recruited to the plasma membrane through OSBPL3 binding (PubMed:25447204).
The OSBPL3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:25447204).
With OSBPL3, may regulate ER morphology (PubMed:16143324).
May play a role in vesicle trafficking (PubMed:11511104, 19289470).
Endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000269 PubMed:10523508, 16143324, 19289470, 25447204, 30741634, 32344433, 33124732, 10523508, 19289470}
Cell membrane; Single-pass type IV membrane protein {ECO:0000269 PubMed:25447204 | ECO:0000305}
Cell junction, tight junction {ECO:0000269 PubMed:10523508}
Nucleus membrane {ECO:0000250 UniProtKB:Q9Z270}
Note: Present in the plasma membrane and in intracellular vesicles, together with SNARE proteins. May also associate with the cytoskeleton. Colocalizes with OCLN at the tight junction in polarized epithelial cells {ECO:0000269 PubMed:10523508}
Quaternary structure:
Homodimer; disulfide-linked (PubMed:11511104, 33124732).
Heterodimer with VAPB (PubMed:11511104).
Homotetramer (PubMed:33124732).
Interacts with VAMP1, VAMP2, STX1A, BET1, SEC22C and with the C-terminal domain of OCLN (PubMed:10523508, 11511104, 9657962).
Interacts (via MSP domain) with OSBPL1A (via FFAT motif) (PubMed:33124732).
Interacts (via MSP domain) with ZFYVE27; may retain ZFYVE27 in the endoplasmic reticulum and regulate its function in cell projections formation (PubMed:19289470, 21976701).
Interacts with OSBP (PubMed:20178991).
Interacts (via C-terminus) with RSAD2/viperin (via C-terminus) (PubMed:21957124).
Interacts with IFITM3 (PubMed:23601107).
Interacts with OSBPL3 (phosphorylated form) (PubMed:16143324, 25447204).
Interacts with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701).
Interacts (via MSP domain) with STARD3 (via phosphorylated FFAT motif); this interaction recruits VAPA to the endosome (PubMed:24105263, 33124732).
Interacts with STARD3NL (via FFAT motif) (PubMed:24105263).
Interacts with CERT1 (PubMed:16895911).
Interacts with PLEKHA3 and SACM1L to form a ternary complex (PubMed:30659099).
Interacts with VPS13A (via FFAT motif) (PubMed:30741634).
Interacts with RB1CC1 (via phosphorylated FFAT motif), MIGA2 (via phosphorylated FFAT motif), RMDN3 (via phosphorylated FFAT motif), KCNB1 (via phosphorylated FFAT motif) and KCNB2 (via phosphorylated FFAT motif) (PubMed:33124732).
Interacts (via MSP domain) with WDR44 (via FFAT-like motif); the interactions connect the endoplasmic reticulum (ER) with the endosomal tubule (PubMed:32344433). |
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