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Reviewed, UniProtKB/Swiss-Prot O95292 (VAPB_HUMAN)

Last modified March 2, 2010. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
Vesicle-associated membrane protein-associated protein B/C
Short name=VAMP-associated protein B/C
Short name=VAMP-B/VAMP-C
Short name=VAP-B/VAP-C
Gene names
Name:VAPB
ORF Names:UNQ484/PRO983
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length243 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

May play a role in vesicle trafficking.

Subunit structure

Homodimer, and heterodimer with VAPA. Interacts with VAMP1 and VAMP2. Interacts with HCV NS5A and NS5B. Ref.7

Subcellular location

Cell membrane; Single-pass type IV membrane protein By similarity. Endomembrane system; Single-pass type IV membrane protein By similarity. Note: Present in the plasma membrane and in intracellular vesicles By similarity.

Tissue specificity

Ubiquitous. Isoform 1 predominates.

Involvement in disease

Defects in VAPB are the cause of amyotrophic lateral sclerosis type 8 (ALS8) [MIM:608627]. ALS8 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. 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 cases leading to familial forms. Ref.15

Defects in VAPB are a cause of spinal muscular atrophy autosomal dominant Finkel type (SMAF) [MIM:182980]; also called late-onset spinal muscular atrophy Finkel type or spinal muscular atrophy proximal adult autosomal dominant. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAF 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.

Sequence similarities

Contains 1 MSP domain.

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Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseAmyotrophic lateral sclerosis
Disease mutation
Neurodegeneration
   DomainCoiled coil
Transmembrane
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processcell death

Inferred from electronic annotation. Source: UniProtKB-KW

endoplasmic reticulum unfolded protein response

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of viral genome replication Ref.7

Inferred from mutant phenotype. Source: UniProtKB

virus-host interaction Ref.7

Inferred from direct assay. Source: UniProtKB

   Cellular componentGolgi apparatus Ref.7

Inferred from direct assay. Source: UniProtKB

endoplasmic reticulum membrane Ref.7

Inferred from direct assay. Source: UniProtKB

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionbeta-tubulin binding

Inferred from direct assay. Source: UniProtKB

enzyme binding

Inferred from physical interaction. Source: UniProtKB

protein heterodimerization activity Ref.1 Ref.7

Inferred from physical interaction. Source: UniProtKB

protein homodimerization activity Ref.1 Ref.7

Inferred from physical interaction. Source: UniProtKB

structural molecule activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

Epha4Q031371EBI-1188298,EBI-1539152From a different organism.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95292-1)

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.
Isoform 2 (identifier: O95292-2)

Also known as: VAP-C;

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6
Chain2 – 243242Vesicle-associated membrane protein-associated protein B/C
PRO_0000213473

Regions

Topological domain2 – 222221Cytoplasmic Potential
Transmembrane223 – 24321Anchor for type IV membrane protein Potential
Domain7 – 124118MSP
Coiled coil159 – 19638 Potential

Amino acid modifications

Modified residue21N-acetylalanine Ref.13
Modified residue31N6-acetyllysine Ref.14
Modified residue1501Phosphothreonine Ref.10 Ref.11
Modified residue1561Phosphoserine Ref.13 Ref.11
Modified residue1591Phosphoserine Ref.8
Modified residue1601Phosphoserine Ref.13 Ref.10 Ref.11 Ref.8
Modified residue2061Phosphoserine Ref.13 Ref.10 Ref.9

Natural variations

Alternative sequence71 – 9929VMLQP…APTDT → GRRWTADEEDSAEQQPHFSI SPNWEGRRP in isoform 2.
VSP_003277
Alternative sequence100 – 243144Missing in isoform 2.
VSP_003278
Natural variant561P → S in ALS8 and SMAF. Ref.15
VAR_026743

Experimental info

Sequence conflict601I → V in AAF67013. Ref.2
Sequence conflict671I → L in AAF67013. Ref.2
Sequence conflict971T → P in AAF67013. Ref.2
Sequence conflict103 – 1064EAVW → DGTR in AAF67013. Ref.2

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (VAP-B) [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 22AEEF9EC7FC0B3F

FASTA24327,228
        10         20         30         40         50         60 
MAKVEQVLSL EPQHELKFRG PFTDVVTTNL KLGNPTDRNV CFKVKTTAPR RYCVRPNSGI 

        70         80         90        100        110        120 
IDAGASINVS VMLQPFDYDP NEKSKHKFMV QSMFAPTDTS DMEAVWKEAK PEDLMDSKLR 

       130        140        150        160        170        180 
CVFELPAEND KPHDVEINKI ISTTASKTET PIVSKSLSSS LDDTEVKKVM EECKRLQGEV 

       190        200        210        220        230        240 
QRLREENKQF KEEDGLRMRK TVQSNSPISA LAPTGKEEGL STRLLALVVL FFIVGVIIGK 


IAL

« Hide

Isoform 2 (VAP-C).

Checksum: 042285C56B89CCDC
Show »

FASTA9911,152

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References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins."
Nishimura Y., Hayashi M., Inada H., Tanaka T.
Biochem. Biophys. Res. Commun. 254:21-26(1999) [PubMed: 9920726] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Heart.
[2]"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning."
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. expand/collapse author list , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed: 10931946] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Adrenal gland.
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed: 11780052] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lymph.
[6]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-19.
Tissue: Platelet.
[7]"Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B."
Hamamoto I., Nishimura Y., Okamoto T., Aizaki H., Liu M., Mori Y., Abe T., Suzuki T., Lai M.M., Miyamura T., Moriishi K., Matsuura Y.
J. Virol. 79:13473-13482(2005) [PubMed: 16227268] [Abstract]
Cited for: INTERACTION WITH HCV NS5A AND NS5B.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159 AND SER-160, MASS SPECTROMETRY.
Tissue: Epithelium.
[9]"Phosphoproteome analysis of the human mitotic spindle."
Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R.
Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206, MASS SPECTROMETRY.
Tissue: Epithelium.
[10]"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis."
Wang B., Malik R., Nigg E.A., Korner R.
Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-150; SER-160 AND SER-206, MASS SPECTROMETRY.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-150; SER-156 AND SER-160, MASS SPECTROMETRY.
[12]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156; SER-160 AND SER-206, MASS SPECTROMETRY.
[14]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-3, MASS SPECTROMETRY.
[15]"A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis."
Nishimura A.L., Mitne-Neto M., Silva H.C., Richieri-Costa A., Middleton S., Cascio D., Kok F., Oliveira J.R., Gillingwater T., Webb J., Skehel P., Zatz M.
Am. J. Hum. Genet. 75:822-831(2004) [PubMed: 15372378] [Abstract]
Cited for: VARIANT ALS8/SMAF SER-56.
+Additional computationally mapped references.

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Web resources

Alsod

ALS genetic mutations db

GeneReviews

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00006211.
IPI00748221.
PIRJG0186.
RefSeqNP_004729.1.
UniGeneHs.182625

3D structure databases

SMRO95292. Positions 1-134.
ModBaseSearch...

Protein-protein interaction databases

IntActO95292. 4 interactions.
STRINGO95292.

Protein family/group databases

TCDB9.B.17.1.1. VAMP-associated protein (VAP) family.

PTM databases

PhosphoSiteO95292.

Proteomic databases

PRIDEO95292.

Genome annotation databases

EnsemblENST00000475243; ENSP00000417175; ENSG00000124164; Homo sapiens. [Genome view]
GeneID9217.
KEGGhsa:9217.
UCSCuc002xza.1. human.

Organism-specific databases

CTD9217.
GeneCardsGC20P056397.
H-InvDBHIX0015950.
HGNCHGNC:12649. VAPB.
HPACAB013722.
HPA013144.
MIM182980. phenotype.
605704. gene.
608627. phenotype.
Orphanet209335. Adult-onset proximal spinal muscular atrophy, autosomal dominant.
803. Amyotrophic lateral sclerosis.
PharmGKBPA37273.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14301.
HOGENOMHBG446464.
HOVERGENHBG028551.
InParanoidO95292.
OMAVMSKSIS.
OrthoDBEOG9W1101.
PhylomeDBO95292.

Enzyme and pathway databases

ReactomeREACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpressO95292.
BgeeO95292.
CleanExHS_VAPB.
GenevestigatorO95292.
GermOnlineENSG00000124164. Homo sapiens.

Family and domain databases

InterProIPR000535. Major_sperm.
IPR008962. PapD-like.
IPR016763. Vesicle-associated_membrane.
[Graphical view]
Gene3DG3DSA:2.60.40.360. MSP. 1 hit.
PfamPF00635. Motile_Sperm. 1 hit.
[Graphical view]
PIRSFPIRSF019693. VAMP-associated. 1 hit.
SUPFAMSSF49354. PapD-like. 1 hit.
PROSITEPS50202. MSP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio34553.
SOURCESearch...

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Entry information

Entry nameVAPB_HUMAN
AccessionPrimary (citable) accession number: O95292
Secondary accession number(s): A2A2F2, O95293, Q9P0H0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: January 23, 2007
Last modified: March 2, 2010
This is version 96 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Human chromosome 20: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents