Q9P0L0 (VAPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vesicle-associated membrane protein-associated protein A
Short name=VAMP-A
Short name=VAMP-associated protein A
Short name=VAP-A

Alternative name(s):
33 kDa VAMP-associated protein
Short name=VAP-33

Gene names

Name:	VAPA
Synonyms:	VAP33

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	249 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in vesicle trafficking. Ref.9 Ref.10
Subunit structure	Homodimer, and heterodimer with VAPB. Interacts with VAMP1, VAMP2, STX1A, BET1, SEC22C and with the C-terminal domain of OCLN. Interacts with OSBPL1A. Interacts (via MSP domain) with ZFYVE27; may retain ZFYVE27 in the endoplasmic reticulum and regulate its function in cell projections formation. Interacts with OSBP. Interacts (via C-terminus) with RSAD2/viperin (via C-terminus). Interacts with HCV protein NS5A and NS5B. Ref.1 Ref.6 Ref.9 Ref.10 Ref.13 Ref.14
Subcellular location	Endoplasmic reticulum membrane; Single-pass type IV membrane protein. Note: Present in the plasma membrane and in intracellular vesicles, together with SNARE proteins. May also associate with the cytoskeleton. Colocalizes with OCLN at the tight junction in polarized epithelial cells. Ref.1 Ref.10
Tissue specificity	Ubiquitous.
Sequence similarities	Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family. [View classification] Contains 1 MSP domain.
Sequence caution	The sequence AAD09742.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAF72105.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BG488667 differs from that shown. Reason: Frameshift at positions 72, 207 and 241.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Transmembrane Transmembrane helix
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from mutant phenotype Ref.10. Source: UniProtKB cellular membrane fusion Traceable author statement Ref.6. Source: ProtInc neuron projection development Inferred from mutant phenotype Ref.10. Source: UniProtKB phospholipid metabolic process Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB protein localization to endoplasmic reticulum Inferred from mutant phenotype Ref.10. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome sphingolipid biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microtubule Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB vesicle Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	signal transducer activity Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EGFR	P00533	2	EBI-1059156,EBI-297353
ZFYVE27	Q5T4F4	5	EBI-1059156,EBI-3892947

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9P0L0-1)

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.

Isoform 2 (identifier: Q9P0L0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     139-139: L → LGITPPGNAPTVTSMSSINNTVATPASYHTKDDPRGLSVLKQEKQK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 249

249

Vesicle-associated membrane protein-associated protein A

PRO_0000213470

Regions

Topological domain

1 – 227

227

Cytoplasmic Potential

Transmembrane

228 – 248

21

Helical; Anchor for type IV membrane protein; Potential

Domain

14 – 131

118

MSP

Coiled coil

169 – 205

37

Potential

Amino acid modifications

Modified residue

125

1

N6-acetyllysine Ref.11

Natural variations

Alternative sequence

139

1

L → LGITPPGNAPTVTSMSSINN TVATPASYHTKDDPRGLSVL KQEKQK in isoform 2.

VSP_038648

Natural variant

8

1

M → T.
Corresponds to variant rs1044163 [ dbSNP | Ensembl ].

VAR_050440

Natural variant

104

1

P → L.
Corresponds to variant rs1127666 [ dbSNP | Ensembl ].

VAR_050441

Experimental info

Mutagenesis

94

1

K → D: Alters interaction with ZFYVE27; when associated with D-96. Ref.10

Mutagenesis

96

1

M → D: Alters interaction with ZFYVE27; when associated with D-94. Ref.10

Sequence conflict

10 – 11

2

KH → ND in AAC26508. Ref.6

Sequence conflict

10 – 11

2

KH → ND in AAV38424. Ref.8

Sequence conflict

160

1

P → S in AAF72105. Ref.2

Secondary structure

1

.

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249

Helix Strand Turn

Details...

Beta strand

14 – 21

8

Beta strand

23 – 27

5

Beta strand

33 – 40

8

Beta strand

43 – 45

3

Beta strand

47 – 54

8

Turn

56 – 58

3

Beta strand

59 – 63

5

Beta strand

65 – 68

4

Beta strand

73 – 80

8

Beta strand

94 – 101

8

Helix

109 – 115

7

Turn

118 – 120

3

Beta strand

122 – 131

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 9, 2007. Version 3. Checksum: 68B603F3A9FA5475	FASTA	249	27,893
	10 20 30 40 50 60 MASASGAMAK HEQILVLDPP TDLKFKGPFT DVVTTNLKLR NPSDRKVCFK VKTTAPRRYC 70 80 90 100 110 120 VRPNSGIIDP GSTVTVSVML QPFDYDPNEK SKHKFMVQTI FAPPNTSDME AVWKEAKPDE 130 140 150 160 170 180 LMDSKLRCVF EMPNENDKLN DMEPSKAVPL NASKQDGPMP KPHSVSLNDT ETRKLMEECK 190 200 210 220 230 240 RLQGEMMKLS EENRHLRDEG LRLRKVAHSD KPGSTSTASF RDNVTSPLPS LLVVIAAIFI GFFLGKFIL
	Isoform 2 [UniParc]. Checksum: 8B2D033706621878	FASTA	294	32,614
	10 20 30 40 50 60 MASASGAMAK HEQILVLDPP TDLKFKGPFT DVVTTNLKLR NPSDRKVCFK VKTTAPRRYC 70 80 90 100 110 120 VRPNSGIIDP GSTVTVSVML QPFDYDPNEK SKHKFMVQTI FAPPNTSDME AVWKEAKPDE 130 140 150 160 170 180 LMDSKLRCVF EMPNENDKLG ITPPGNAPTV TSMSSINNTV ATPASYHTKD DPRGLSVLKQ 190 200 210 220 230 240 EKQKNDMEPS KAVPLNASKQ DGPMPKPHSV SLNDTETRKL MEECKRLQGE MMKLSEENRH 250 260 270 280 290 LRDEGLRLRK VAHSDKPGST STASFRDNVT SPLPSLLVVI AAIFIGFFLG KFIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"VAP-33 localizes to both an intracellular vesicle population and with occludin at the tight junction." Lapierre L.A., Tuma P.L., Navarre J., Goldenring J.R., Anderson J.M. J. Cell Sci. 112:3723-3732(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH OCLN. Tissue: Liver.
[2]	"Cloning and isolating human 33kDa Vamp-associated protein cDNA." Zhou H.J., Huang X.W., Zhou Y., Hu S.L., Yuan J.G., Qiang B.Q. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-199 (ISOFORM 2). Tissue: Lung.
[6]	"Identification of a human homologue of the vesicle-associated membrane protein (VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed protein that binds to VAMP." Weir M.L., Klip A., Trimble W.S. Biochem. J. 333:247-251(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-249 (ISOFORM 1), INTERACTION WITH VAMP1 AND VAMP2. Tissue: Pancreatic islet.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-249 (ISOFORM 1). Tissue: B-cell.
[8]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-249 (ISOFORM 1).
[9]	"VAP-A binds promiscuously to both v- and tSNAREs." Weir M.L., Xie H., Klip A., Trimble W.S. Biochem. Biophys. Res. Commun. 286:616-621(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH VAPB; VAMP1; VAMP2; STX1A; BET1 AND SEC22C.
[10]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZFYVE27, MUTAGENESIS OF LYS-94 AND MET-96, SUBCELLULAR LOCATION.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-125, MASS SPECTROMETRY.
[12]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33." Wang S., Wu X., Pan T., Song W., Wang Y., Zhang F., Yuan Z. J. Gen. Virol. 93:83-92(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RSAD2 AND HCV PROTEIN NS5A AND NS5B.
[14]	"Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies." Furuita K., Jee J., Fukada H., Mishima M., Kojima C. J. Biol. Chem. 285:12961-12970(2010) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 11-135, INTERACTION WITH OSBP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF044670 mRNA. Translation: AAD09742.1. Different initiation.
AF154847 mRNA. Translation: AAF72105.1. Different initiation.
AC006238 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01591.1.
CH471113 Genomic DNA. Translation: EAX01592.1.
BC002992 mRNA. Translation: AAH02992.2.
BG488667 mRNA. No translation available.
AF057358 mRNA. Translation: AAC26508.1.
AF086627 mRNA. Translation: AAD13576.1.
BT019618 mRNA. Translation: AAV38424.1.

IPI

IPI00170692.
IPI00374657.

RefSeq

NP_003565.4. NM_003574.5.
NP_919415.2. NM_194434.2.

UniGene

Hs.165195.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RR3	NMR	-	A	11-135	[»]

ProteinModelPortal

Q9P0L0.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P0L0. 31 interactions.

STRING

9606.ENSP00000345656.

PTM databases

PhosphoSite

Q9P0L0.

Polymorphism databases

DMDM

122066680.

Proteomic databases

PaxDb

Q9P0L0.

PRIDE

Q9P0L0.

Protocols and materials databases

DNASU

9218.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340541; ENSP00000345656; ENSG00000101558.
ENST00000400000; ENSP00000382880; ENSG00000101558.

GeneID

9218.

KEGG

hsa:9218.

UCSC

uc002koj.3. human.
uc002kok.3. human.

Organism-specific databases

CTD

9218.

GeneCards

GC18P009904.

H-InvDB

HIX0115359.

HGNC

HGNC:12648. VAPA.

HPA

HPA009174.

MIM

605703. gene.

neXtProt

NX_Q9P0L0.

PharmGKB

PA37272.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5066.

HOGENOM

HOG000293182.

HOVERGEN

HBG028551.

KO

K06096.

OMA

PNISDME.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9P0L0.

Bgee

Q9P0L0.

CleanEx

HS_VAPA.

Genevestigator

Q9P0L0.

GermOnline

ENSG00000101558. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.360. 1 hit.

InterPro

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

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

ChiTaRS

VAPA. human.

EvolutionaryTrace

Q9P0L0.

GenomeRNAi

9218.

NextBio

34557.

PMAP-CutDB

Q9P0L0.

SOURCE

Search...

Entry information

Entry name

VAPA_HUMAN

Accession

Primary (citable) accession number: Q9P0L0
Secondary accession number(s): A6NDZ0 , D3DUI3, O75453, Q5U0E7, Q9UBZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 2002
Last sequence update:	January 9, 2007
Last modified:	May 1, 2013
This is version 120 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.