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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	249 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. Ref.9 Ref.11
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. Ref.1 Ref.6 Ref.9 Ref.11
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.11
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.11. Source: UniProtKB cellular membrane fusion Traceable author statement. Source: ProtInc neuron projection development Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: UniProtKB protein localization in endoplasmic reticulum Inferred from mutant phenotype Ref.11. Source: UniProtKB sphingolipid metabolic 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 plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB vesicle Inferred from direct assay Ref.1. Source: UniProtKB
Molecular function	protein heterodimerization activity Inferred from physical interaction Ref.7. Source: UniProtKB signal transducer activity Inferred from mutant phenotype. 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

Initiator methionine

1

1

Removed

Chain

2 – 249

248

Vesicle-associated membrane protein-associated protein A

PRO_0000213470

Regions

Topological domain

2 – 227

226

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

2

1

N-acetylalanine Ref.10

Modified residue

125

1

N6-acetyllysine Ref.12

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.11

Mutagenesis

96

1

M → D: Alters interaction with ZFYVE27; when associated with D-94. Ref.11

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

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

249

Helix Strand Turn

Details...

Beta strand

14 – 21

8

Beta strand

23 – 25

3

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

73 – 80

8

Beta strand

94 – 101

8

Helix

109 – 115

7

Beta strand

122 – 130

9

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: 10523508] [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: 16177791] [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: 15489334] [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: 9657962] [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: 9920726] [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: 11511104] [Abstract] Cited for: FUNCTION, INTERACTION WITH VAPB; VAMP1; VAMP2; STX1A; BET1 AND SEC22C.
[10]	"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, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"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: FUNCTION, INTERACTION WITH ZFYVE27, MUTAGENESIS OF LYS-94 AND MET-96, SUBCELLULAR LOCATION.
[12]	"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-125, MASS SPECTROMETRY.
[13]	"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].
+	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.

SMR

Q9P0L0. Positions 9-135.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P0L0. 22 interactions.

STRING

Q9P0L0.

PTM databases

PhosphoSite

Q9P0L0.

Polymorphism databases

DMDM

122066680.

Proteomic databases

PRIDE

Q9P0L0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000400000; ENSP00000382880; ENSG00000101558.

GeneID

9218.

KEGG

hsa:9218.

UCSC

uc002kok.1. human.

Organism-specific databases

CTD

9218.

GeneCards

GC18P009904.

H-InvDB

HIX0014330.

HGNC

HGNC:12648. VAPA.

HPA

HPA009174.

MIM

605703. gene.

neXtProt

NX_Q9P0L0.

PharmGKB

PA37272.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17459.

GeneTree

ENSGT00390000006947.

HOVERGEN

HBG028551.

OMA

TASFRDN.

PhylomeDB

Q9P0L0.

Enzyme and pathway databases

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q9P0L0.

Bgee

Q9P0L0.

CleanEx

HS_VAPA.

Genevestigator

Q9P0L0.

GermOnline

ENSG00000101558. 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

K06096.

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

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:	January 25, 2012
This is version 107 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.