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Protein

Vesicle-associated membrane protein-associated protein B/C

Gene

VAPB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 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

Keywordsi

Biological processHost-virus interaction, Unfolded protein response

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000124164.15
HGNCiHGNC:12649 VAPB
MIMi605704 gene
neXtProtiNX_O95292

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Amyotrophic lateral sclerosis 8 (ALS8)4 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 dbSNP:rs281875284Ensembl.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

Keywords - Diseasei

Amyotrophic lateral sclerosis, Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi9217
GeneReviewsiVAPB
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 (via MSP domain) with ZFYVE27 (PubMed:21976701, PubMed:19289470). Interacts with RMDN3 (PubMed:22131369). Interacts with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701). Interacts with STARD3 (via FFAT motif) (PubMed:24105263). Interacts with STARD3NL (via FFAT motif) (PubMed:24105263).7 Publications
(Microbial infection) Interacts with HCV protein NS5A and NS5B.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • beta-tubulin binding Source: UniProtKB
  • cadherin binding 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

BioGridi114650166 interactors.
CORUMiO95292
DIPiDIP-39816N
IntActiO95292 51 interactors.
MINTiO95292
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

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.101 hit
InterProiView protein in InterPro
IPR013783 Ig-like_fold
IPR000535 MSP_dom
IPR008962 PapD-like_sf
IPR016763 VAP
IPR030226 VapB
PANTHERiPTHR10809 PTHR10809, 1 hit
PTHR10809:SF12 PTHR10809:SF12, 1 hit
PfamiView protein in Pfam
PF00635 Motile_Sperm, 1 hit
PIRSFiPIRSF019693 VAMP-associated, 1 hit
SUPFAMiSSF49354 SSF49354, 1 hit
PROSITEiView protein in PROSITE
PS50202 MSP, 1 hit

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 dbSNP:rs281875284Ensembl.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 dbSNP:rs74315431Ensembl.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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiVAPB_HUMAN
AccessioniPrimary (citable) accession number: O95292
Secondary accession number(s): A2A2F2, O95293, Q9P0H0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 178 of the entry and version 3 of the sequence. See 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