O95292 · VAPB_HUMAN
- ProteinVesicle-associated membrane protein-associated protein B/C
- GeneVAPB
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids243 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 43 | Involved in binding the phosphorylated serine of the phospho-FFAT motif | ||||
Sequence: K |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameVesicle-associated membrane protein-associated protein B/C
- Short namesVAMP-B/VAMP-C; VAMP-associated protein B/C; VAP-B/VAP-C
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO95292
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 2-222 | Cytoplasmic | ||||
Sequence: AKVEQVLSLEPQHELKFRGPFTDVVTTNLKLGNPTDRNVCFKVKTTAPRRYCVRPNSGIIDAGASINVSVMLQPFDYDPNEKSKHKFMVQSMFAPTDTSDMEAVWKEAKPEDLMDSKLRCVFELPAENDKPHDVEINKIISTTASKTETPIVSKSLSSSLDDTEVKKVMEECKRLQGEVQRLREENKQFKEEDGLRMRKTVQSNSPISALAPTGKEEGLST | ||||||
Transmembrane | 223-243 | Helical; Anchor for type IV membrane protein | ||||
Sequence: RLLALVVLFFIVGVIIGKIAL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Amyotrophic lateral sclerosis 8 (ALS8)
- Note
- DescriptionA 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.
- See alsoMIM:608627
Natural variants in ALS8
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_067964 | 46 | T>I | in ALS8; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway through ERN1/IRE1 induction; results in ubiquitinated aggregates accumulation and cell death; dbSNP:rs281875284 | |
VAR_026743 | 56 | P>S | in ALS8 and SMAPAD; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway; affects interaction with RMDN3; affects cellular calcium homeostasis; induces mislocalization to the non-ER compartments; enhances homodimerization; dbSNP:rs74315431 |
Spinal muscular atrophy, proximal, adult, autosomal dominant (SMAPAD)
- Note
- DescriptionA 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.
- See alsoMIM:182980
Natural variants in SMAPAD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_026743 | 56 | P>S | in ALS8 and SMAPAD; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway; affects interaction with RMDN3; affects cellular calcium homeostasis; induces mislocalization to the non-ER compartments; enhances homodimerization; dbSNP:rs74315431 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 43 | Does not affect interaction with the conventional FFAT motif of OSBPL1A. Impairs the interactions of the MSP domain with the phosphorylated FFAT motif of STARD3. | ||||
Sequence: K → L | ||||||
Natural variant | VAR_067964 | 46 | in ALS8; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway through ERN1/IRE1 induction; results in ubiquitinated aggregates accumulation and cell death; dbSNP:rs281875284 | |||
Sequence: T → I | ||||||
Natural variant | VAR_026743 | 56 | in ALS8 and SMAPAD; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway; affects interaction with RMDN3; affects cellular calcium homeostasis; induces mislocalization to the non-ER compartments; enhances homodimerization; dbSNP:rs74315431 | |||
Sequence: P → S | ||||||
Mutagenesis | 87 | Prevents binding to the FFAT motif in target proteins; when associated with D-89. | ||||
Sequence: K → D | ||||||
Mutagenesis | 89 | Prevents binding to the FFAT motif in target proteins; when associated with D-87. | ||||
Sequence: M → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 251 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000213473 | 2-243 | UniProt | Vesicle-associated membrane protein-associated protein B/C | |||
Sequence: AKVEQVLSLEPQHELKFRGPFTDVVTTNLKLGNPTDRNVCFKVKTTAPRRYCVRPNSGIIDAGASINVSVMLQPFDYDPNEKSKHKFMVQSMFAPTDTSDMEAVWKEAKPEDLMDSKLRCVFELPAENDKPHDVEINKIISTTASKTETPIVSKSLSSSLDDTEVKKVMEECKRLQGEVQRLREENKQFKEEDGLRMRKTVQSNSPISALAPTGKEEGLSTRLLALVVLFFIVGVIIGKIAL | |||||||
Modified residue (large scale data) | 142 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 143 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 146 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 146 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 147 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 148 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 150 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 150 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 156 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 156 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 158 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 158 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 159 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 159 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 160 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 160 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 164 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 206 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 206 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with VAMP1 and VAMP2 (PubMed:20940299, PubMed:9920726).
Interacts (via MSP domain) with ZFYVE27 (PubMed:19289470, PubMed:21976701).
Interacts with RMDN3 (PubMed:22131369).
Interacts with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701).
Interacts (via MSP domain) with STARD3 (via phospho-FFAT motif) (PubMed:24105263, PubMed: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), OSBPL1A (via FFAT motif), KCNB1 (via phosphorylated FFAT motif) and KCNB2 (via phosphorylated FFAT motif) (PubMed:33124732).
Interacts (via MSP domain) with WDR44 (via FFAT motif); the interactions connect the endoplasmic reticulum (ER) with the endosomal tubule (PubMed:32344433).
Interacts with HCV RNA-directed RNA polymerase (PubMed:16227268).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 7-124 | MSP | ||||
Sequence: VLSLEPQHELKFRGPFTDVVTTNLKLGNPTDRNVCFKVKTTAPRRYCVRPNSGIIDAGASINVSVMLQPFDYDPNEKSKHKFMVQSMFAPTDTSDMEAVWKEAKPEDLMDSKLRCVFE | ||||||
Coiled coil | 159-196 | |||||
Sequence: SSLDDTEVKKVMEECKRLQGEVQRLREENKQFKEEDGL |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O95292-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsVAP-B
- Length243
- Mass (Da)27,228
- Last updated2007-01-23 v3
- Checksum22AEEF9EC7FC0B3F
O95292-2
- Name2
- SynonymsVAP-C
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E5RK64 | E5RK64_HUMAN | VAPB | 71 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 60 | in Ref. 2; AAF67013 | ||||
Sequence: I → V | ||||||
Sequence conflict | 67 | in Ref. 2; AAF67013 | ||||
Sequence: I → L | ||||||
Alternative sequence | VSP_003277 | 71-99 | in isoform 2 | |||
Sequence: VMLQPFDYDPNEKSKHKFMVQSMFAPTDT → GRRWTADEEDSAEQQPHFSISPNWEGRRP | ||||||
Sequence conflict | 97 | in Ref. 2; AAF67013 | ||||
Sequence: T → P | ||||||
Alternative sequence | VSP_003278 | 100-243 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 103-106 | in Ref. 2; AAF67013 | ||||
Sequence: EAVW → DGTR |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF086628 EMBL· GenBank· DDBJ | AAD13577.1 EMBL· GenBank· DDBJ | mRNA | ||
AF086629 EMBL· GenBank· DDBJ | AAD13578.1 EMBL· GenBank· DDBJ | mRNA | ||
AF160212 EMBL· GenBank· DDBJ | AAF67013.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358464 EMBL· GenBank· DDBJ | AAQ88829.1 EMBL· GenBank· DDBJ | mRNA | ||
AL035455 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC001712 EMBL· GenBank· DDBJ | AAH01712.1 EMBL· GenBank· DDBJ | mRNA |