O95292 (VAPB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	VAPB
ORF Names:	UNQ484/PRO983

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	243 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

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. Interacts (via MSP domain) with ZFYVE27. Ref.7 Ref.13
Subcellular location	Endoplasmic reticulum membrane; Single-pass type IV membrane protein 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.16 Defects in VAPB are a cause of spinal muscular atrophy proximal adult autosomal dominant (SMAPAD) [MIM:182980]; also called late-onset spinal muscular atrophy Finkel type. A 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. Ref.16
Sequence similarities	Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family. [View classification] Contains 1 MSP domain.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Disease	Amyotrophic lateral sclerosis Disease mutation Neurodegeneration
Domain	Coiled coil Transmembrane Transmembrane helix
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell 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 Inferred from mutant phenotype Ref.7. Source: UniProtKB sphingolipid metabolic process Traceable author statement. Source: Reactome virus-host interaction Inferred from direct assay Ref.7. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay Ref.7. Source: UniProtKB endoplasmic reticulum membrane Inferred from direct assay Ref.7. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	beta-tubulin binding Inferred from direct assay. Source: UniProtKB enzyme binding Inferred from physical interaction. Source: UniProtKB protein heterodimerization activity Inferred from physical interaction Ref.7Ref.1. Source: UniProtKB protein homodimerization activity Inferred from physical interaction Ref.7Ref.1. Source: UniProtKB structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Epha4	Q03137	2	EBI-1188298,EBI-1539152	From a different organism.
ZFYVE27	Q5T4F4	2	EBI-1188298,EBI-3892947

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 243

242

Vesicle-associated membrane protein-associated protein B/C

PRO_0000213473

Regions

Topological domain

2 – 222

221

Cytoplasmic Potential

Transmembrane

223 – 243

21

Helical; Anchor for type IV membrane protein; Potential

Domain

7 – 124

118

MSP

Coiled coil

159 – 196

38

Potential

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.12

Modified residue

3

1

N6-acetyllysine Ref.14

Modified residue

150

1

Phosphothreonine Ref.10 Ref.11

Modified residue

156

1

Phosphoserine Ref.11 Ref.12

Modified residue

159

1

Phosphoserine Ref.8

Modified residue

160

1

Phosphoserine Ref.8 Ref.10 Ref.11 Ref.12

Modified residue

206

1

Phosphoserine Ref.9 Ref.10 Ref.12

Natural variations

Alternative sequence

71 – 99

29

VMLQP…APTDT → GRRWTADEEDSAEQQPHFSI SPNWEGRRP in isoform 2.

VSP_003277

Alternative sequence

100 – 243

144

Missing in isoform 2.

VSP_003278

Natural variant

56

1

P → S in ALS8 and SMAPAD. Ref.16

VAR_026743

Experimental info

Sequence conflict

60

1

I → V in AAF67013. Ref.2

Sequence conflict

67

1

I → L in AAF67013. Ref.2

Sequence conflict

97

1

T → P in AAF67013. Ref.2

Sequence conflict

103 – 106

4

EAVW → DGTR in AAF67013. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

243

Helix Strand Turn

Details...

Beta strand

11 – 18

8

Beta strand

26 – 32

7

Beta strand

36 – 38

3

Beta strand

40 – 47

8

Turn

49 – 51

3

Beta strand

52 – 56

5

Beta strand

67 – 73

7

Beta strand

88 – 94

7

Turn

104 – 108

5

Beta strand

111 – 113

3

Beta strand

115 – 123

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (VAP-B) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 22AEEF9EC7FC0B3F	FASTA	243	27,228
	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
	Isoform 2 (VAP-C) [UniParc]. Checksum: 042285C56B89CCDC	FASTA	99	11,152
	10 20 30 40 50 60 MAKVEQVLSL EPQHELKFRG PFTDVVTTNL KLGNPTDRNV CFKVKTTAPR RYCVRPNSGI 70 80 90 IDAGASINVS GRRWTADEED SAEQQPHFSI SPNWEGRRP

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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: Cervix carcinoma.
[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: Cervix adenocarcinoma.
[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. Tissue: Cervix carcinoma.
[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. Tissue: Cervix carcinoma.
[12]	"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. Tissue: Embryonic kidney.
[13]	"Promotion of neurite extension by protrudin requires its interaction with vesicle-associated membrane protein-associated protein." Saita S., Shirane M., Natume T., Iemura S., Nakayama K.I. J. Biol. Chem. 284:13766-13777(2009) [PubMed: 19289470] [Abstract] Cited for: INTERACTION WITH ZFYVE27.
[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]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"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 SER-56, VARIANT SMAPAD SER-56.
+	Additional computationally mapped references.

Web resources

Alsod

ALS genetic mutations db

GeneReviews

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.

IPI

IPI00006211.
IPI00748221.

PIR

JG0186.

RefSeq

NP_001182606.1. NM_001195677.1.
NP_004729.1. NM_004738.4.

UniGene

Hs.182625.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IKK	X-ray	2.50	A/B	1-125	[»]

ProteinModelPortal

O95292.

SMR

O95292. Positions 1-125.

ModBase

Search...

Protein-protein interaction databases

IntAct

O95292. 8 interactions.

STRING

O95292.

Protein family/group databases

TCDB

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

PTM databases

PhosphoSite

O95292.

Proteomic databases

PRIDE

O95292.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000475243; ENSP00000417175; ENSG00000124164.

GeneID

9217.

KEGG

hsa:9217.

UCSC

uc002xza.1. human.

Organism-specific databases

CTD

9217.

GeneCards

GC20P056964.

H-InvDB

HIX0015950.

HGNC

HGNC:12649. VAPB.

HPA

CAB013722.
HPA013144.

MIM

182980. phenotype.
605704. gene.
608627. phenotype.

neXtProt

NX_O95292.

Orphanet

209335. Adult-onset proximal spinal muscular atrophy, autosomal dominant.
803. Amyotrophic lateral sclerosis.

PharmGKB

PA37273.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14301.

HOGENOM

HBG446464.

HOVERGEN

HBG028551.

InParanoid

O95292.

OMA

VMSKSIS.

OrthoDB

EOG4DNF5D.

PhylomeDB

O95292.

Enzyme and pathway databases

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

O95292.

Bgee

O95292.

CleanEx

HS_VAPB.

Genevestigator

O95292.

GermOnline

ENSG00000124164. Homo sapiens.

Family and domain databases

InterPro

IPR000535. Major_sperm.
IPR008962. PapD-like.
IPR016763. Vesicle-associated_membrane.
[Graphical view]

Gene3D

G3DSA:2.60.40.360. MSP. 1 hit.

KO

K10707.

Pfam

PF00635. Motile_Sperm. 1 hit.
[Graphical view]

PIRSF

PIRSF019693. VAMP-associated. 1 hit.

SUPFAM

SSF49354. PapD-like. 1 hit.

PROSITE

PS50202. MSP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

34553.

SOURCE

Search...

Entry information

Entry name

VAPB_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.