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Protein

Vesicle-associated membrane protein-associated protein B/C

Gene

VAPB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Participates in the endoplasmic reticulum unfolded protein response (UPR) by inducing ERN1/IRE1 activity. Involved in cellular calcium homeostasis regulation.3 Publications

GO - Molecular functioni

  • beta-tubulin binding Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • FFAT motif binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • activation of signaling protein activity involved in unfolded protein response Source: UniProtKB
  • cellular calcium ion homeostasis Source: UniProtKB
  • COPII-coated vesicle budding Source: UniProtKB
  • endoplasmic reticulum organization Source: UniProtKB
  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • ER to Golgi vesicle-mediated transport Source: UniProtKB
  • modulation by host of viral RNA genome replication Source: AgBase
  • modulation by virus of host morphology or physiology Source: UniProtKB
  • negative regulation by host of viral genome replication Source: AgBase
  • negative regulation by host of viral release from host cell Source: AgBase
  • negative regulation by virus of viral protein levels in host cell Source: AgBase
  • positive regulation by host of viral genome replication Source: AgBase
  • positive regulation by host of viral release from host cell Source: AgBase
  • positive regulation of viral genome replication Source: UniProtKB
  • sphingolipid biosynthetic process Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Unfolded protein response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124164-MONOMER.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.

Protein family/group databases

TCDBi9.B.17.1.1. the vamp-associated protein (vap) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Vesicle-associated membrane protein-associated protein B/C
Short name:
VAMP-B/VAMP-C
Short name:
VAMP-associated protein B/C
Short name:
VAP-B/VAP-C
Gene namesi
Name:VAPB
ORF Names:UNQ484/PRO983
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:12649. VAPB.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 222CytoplasmicSequence analysisAdd BLAST221
Transmembranei223 – 243Helical; Anchor for type IV membrane proteinSequence analysisAdd BLAST21

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: GOC
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Amyotrophic lateral sclerosis 8 (ALS8)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:608627
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06796446T → 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. 1 PublicationCorresponds to variant rs281875284dbSNPEnsembl.1
Natural variantiVAR_02674356P → 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. 4 PublicationsCorresponds to variant rs74315431dbSNPEnsembl.1
Spinal muscular atrophy, proximal, adult, autosomal dominant (SMAPAD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:182980
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02674356P → 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. 4 PublicationsCorresponds to variant rs74315431dbSNPEnsembl.1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi9217.
MalaCardsiVAPB.
MIMi182980. phenotype.
608627. phenotype.
OpenTargetsiENSG00000124164.
Orphaneti209335. Adult-onset proximal spinal muscular atrophy, autosomal dominant.
803. Amyotrophic lateral sclerosis.
PharmGKBiPA37273.

Polymorphism and mutation databases

BioMutaiVAPB.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00002134732 – 243Vesicle-associated membrane protein-associated protein B/CAdd BLAST242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei146PhosphoserineCombined sources1
Cross-linki147Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Modified residuei150PhosphothreonineCombined sources1
Modified residuei156PhosphoserineCombined sources1
Modified residuei158PhosphoserineCombined sources1
Modified residuei159PhosphoserineCombined sources1
Modified residuei160PhosphoserineCombined sources1
Modified residuei206PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95292.
PaxDbiO95292.
PeptideAtlasiO95292.
PRIDEiO95292.

PTM databases

iPTMnetiO95292.
PhosphoSitePlusiO95292.
SwissPalmiO95292.

Expressioni

Tissue specificityi

Ubiquitous. Isoform 1 predominates.

Gene expression databases

BgeeiENSG00000124164.
CleanExiHS_VAPB.
ExpressionAtlasiO95292. baseline and differential.
GenevisibleiO95292. HS.

Organism-specific databases

HPAiCAB013722.
HPA013144.

Interactioni

Subunit structurei

Homodimer, and heterodimer with VAPA (PubMed:20940299). Interacts with VAMP1 and VAMP2 (PubMed:9920726, PubMed:20940299). Interacts with HCV NS5A and NS5B (PubMed:16227268). Interacts (via MSP domain) with ZFYVE27 (PubMed:21976701, PubMed:19289470). Interacts with RMDN3 (PubMed:22131369). Interacts with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701).6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q034636EBI-1188298,EBI-8803426From a different organism.
Q99IB82EBI-1188298,EBI-9096996From a different organism.
Epha4Q031372EBI-1188298,EBI-1539152From a different organism.
VAPAQ9P0L02EBI-1188298,EBI-1059156
YIF1AO950709EBI-1188298,EBI-2799703
ZFYVE27Q5T4F42EBI-1188298,EBI-3892947

GO - Molecular functioni

  • beta-tubulin binding Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • FFAT motif binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi114650. 154 interactors.
DIPiDIP-39816N.
IntActiO95292. 47 interactors.
STRINGi9606.ENSP00000417175.

Structurei

Secondary structure

1243
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni4 – 7Combined sources4
Beta strandi8 – 20Combined sources13
Beta strandi26 – 33Combined sources8
Beta strandi36 – 38Combined sources3
Beta strandi40 – 47Combined sources8
Turni49 – 51Combined sources3
Beta strandi52 – 61Combined sources10
Beta strandi66 – 73Combined sources8
Turni82 – 84Combined sources3
Beta strandi88 – 94Combined sources7
Turni104 – 108Combined sources5
Beta strandi111 – 113Combined sources3
Beta strandi115 – 124Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MDKNMR-A1-125[»]
3IKKX-ray2.50A/B1-125[»]
ProteinModelPortaliO95292.
SMRiO95292.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95292.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 124MSPPROSITE-ProRule annotationAdd BLAST118

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili159 – 196Sequence analysisAdd BLAST38

Sequence similaritiesi

Contains 1 MSP domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0439. Eukaryota.
COG5066. LUCA.
GeneTreeiENSGT00390000006947.
HOGENOMiHOG000293182.
HOVERGENiHBG028551.
InParanoidiO95292.
KOiK10707.
OMAiAQKEYPQ.
OrthoDBiEOG091G0KJ2.
PhylomeDBiO95292.
TreeFamiTF317024.

Family and domain databases

Gene3Di2.60.40.360. 1 hit.
InterProiIPR000535. MSP_dom.
IPR008962. PapD-like.
IPR016763. VAP.
IPR030226. VapB.
[Graphical view]
PANTHERiPTHR10809. PTHR10809. 1 hit.
PTHR10809:SF12. PTHR10809:SF12. 1 hit.
PfamiPF00635. Motile_Sperm. 1 hit.
[Graphical view]
PIRSFiPIRSF019693. VAMP-associated. 1 hit.
SUPFAMiSSF49354. SSF49354. 1 hit.
PROSITEiPS50202. MSP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95292-1) [UniParc]FASTAAdd to basket
Also known as: VAP-B

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.

« Hide

        10         20         30         40         50
MAKVEQVLSL EPQHELKFRG PFTDVVTTNL KLGNPTDRNV CFKVKTTAPR
60 70 80 90 100
RYCVRPNSGI IDAGASINVS VMLQPFDYDP NEKSKHKFMV QSMFAPTDTS
110 120 130 140 150
DMEAVWKEAK PEDLMDSKLR CVFELPAEND KPHDVEINKI ISTTASKTET
160 170 180 190 200
PIVSKSLSSS LDDTEVKKVM EECKRLQGEV QRLREENKQF KEEDGLRMRK
210 220 230 240
TVQSNSPISA LAPTGKEEGL STRLLALVVL FFIVGVIIGK IAL
Length:243
Mass (Da):27,228
Last modified:January 23, 2007 - v3
Checksum:i22AEEF9EC7FC0B3F
GO
Isoform 2 (identifier: O95292-2) [UniParc]FASTAAdd to basket
Also known as: VAP-C

The sequence of this isoform differs from the canonical sequence as follows:
     71-99: VMLQPFDYDPNEKSKHKFMVQSMFAPTDT → GRRWTADEEDSAEQQPHFSISPNWEGRRP
     100-243: Missing.

Show »
Length:99
Mass (Da):11,152
Checksum:i042285C56B89CCDC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60I → V in AAF67013 (PubMed:10931946).Curated1
Sequence conflicti67I → L in AAF67013 (PubMed:10931946).Curated1
Sequence conflicti97T → P in AAF67013 (PubMed:10931946).Curated1
Sequence conflicti103 – 106EAVW → DGTR in AAF67013 (PubMed:10931946).Curated4

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06796446T → 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. 1 PublicationCorresponds to variant rs281875284dbSNPEnsembl.1
Natural variantiVAR_02674356P → 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. 4 PublicationsCorresponds to variant rs74315431dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00327771 – 99VMLQP…APTDT → GRRWTADEEDSAEQQPHFSI SPNWEGRRP in isoform 2. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_003278100 – 243Missing in isoform 2. 1 PublicationAdd BLAST144

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF086628 mRNA. Translation: AAD13577.1.
AF086629 mRNA. Translation: AAD13578.1.
AF160212 mRNA. Translation: AAF67013.1.
AY358464 mRNA. Translation: AAQ88829.1.
AL035455 Genomic DNA. Translation: CAC15021.1.
AL035455 Genomic DNA. Translation: CAM27023.1.
BC001712 mRNA. Translation: AAH01712.1.
CCDSiCCDS33498.1. [O95292-1]
CCDS56198.1. [O95292-2]
PIRiJG0186.
RefSeqiNP_001182606.1. NM_001195677.1. [O95292-2]
NP_004729.1. NM_004738.4. [O95292-1]
UniGeneiHs.182625.

Genome annotation databases

EnsembliENST00000395802; ENSP00000379147; ENSG00000124164. [O95292-2]
ENST00000475243; ENSP00000417175; ENSG00000124164. [O95292-1]
GeneIDi9217.
KEGGihsa:9217.
UCSCiuc002xzd.3. human. [O95292-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Alsod

ALS genetic mutations db

Mendelian genes VAMP (vesicle-associated membrane protein)-associated protein B and C (VAPB)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF086628 mRNA. Translation: AAD13577.1.
AF086629 mRNA. Translation: AAD13578.1.
AF160212 mRNA. Translation: AAF67013.1.
AY358464 mRNA. Translation: AAQ88829.1.
AL035455 Genomic DNA. Translation: CAC15021.1.
AL035455 Genomic DNA. Translation: CAM27023.1.
BC001712 mRNA. Translation: AAH01712.1.
CCDSiCCDS33498.1. [O95292-1]
CCDS56198.1. [O95292-2]
PIRiJG0186.
RefSeqiNP_001182606.1. NM_001195677.1. [O95292-2]
NP_004729.1. NM_004738.4. [O95292-1]
UniGeneiHs.182625.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MDKNMR-A1-125[»]
3IKKX-ray2.50A/B1-125[»]
ProteinModelPortaliO95292.
SMRiO95292.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114650. 154 interactors.
DIPiDIP-39816N.
IntActiO95292. 47 interactors.
STRINGi9606.ENSP00000417175.

Protein family/group databases

TCDBi9.B.17.1.1. the vamp-associated protein (vap) family.

PTM databases

iPTMnetiO95292.
PhosphoSitePlusiO95292.
SwissPalmiO95292.

Polymorphism and mutation databases

BioMutaiVAPB.

Proteomic databases

EPDiO95292.
PaxDbiO95292.
PeptideAtlasiO95292.
PRIDEiO95292.

Protocols and materials databases

DNASUi9217.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395802; ENSP00000379147; ENSG00000124164. [O95292-2]
ENST00000475243; ENSP00000417175; ENSG00000124164. [O95292-1]
GeneIDi9217.
KEGGihsa:9217.
UCSCiuc002xzd.3. human. [O95292-1]

Organism-specific databases

CTDi9217.
DisGeNETi9217.
GeneCardsiVAPB.
GeneReviewsiVAPB.
HGNCiHGNC:12649. VAPB.
HPAiCAB013722.
HPA013144.
MalaCardsiVAPB.
MIMi182980. phenotype.
605704. gene.
608627. phenotype.
neXtProtiNX_O95292.
OpenTargetsiENSG00000124164.
Orphaneti209335. Adult-onset proximal spinal muscular atrophy, autosomal dominant.
803. Amyotrophic lateral sclerosis.
PharmGKBiPA37273.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0439. Eukaryota.
COG5066. LUCA.
GeneTreeiENSGT00390000006947.
HOGENOMiHOG000293182.
HOVERGENiHBG028551.
InParanoidiO95292.
KOiK10707.
OMAiAQKEYPQ.
OrthoDBiEOG091G0KJ2.
PhylomeDBiO95292.
TreeFamiTF317024.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124164-MONOMER.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.

Miscellaneous databases

ChiTaRSiVAPB. human.
EvolutionaryTraceiO95292.
GeneWikiiVAPB.
GenomeRNAii9217.
PROiO95292.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124164.
CleanExiHS_VAPB.
ExpressionAtlasiO95292. baseline and differential.
GenevisibleiO95292. HS.

Family and domain databases

Gene3Di2.60.40.360. 1 hit.
InterProiIPR000535. MSP_dom.
IPR008962. PapD-like.
IPR016763. VAP.
IPR030226. VapB.
[Graphical view]
PANTHERiPTHR10809. PTHR10809. 1 hit.
PTHR10809:SF12. PTHR10809:SF12. 1 hit.
PfamiPF00635. Motile_Sperm. 1 hit.
[Graphical view]
PIRSFiPIRSF019693. VAMP-associated. 1 hit.
SUPFAMiSSF49354. SSF49354. 1 hit.
PROSITEiPS50202. MSP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVAPB_HUMAN
AccessioniPrimary (citable) accession number: O95292
Secondary accession number(s): A2A2F2, O95293, Q9P0H0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 164 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.