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Protein

Vesicle-associated membrane protein-associated protein A

Gene

VAPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Binds to OSBPL3, which mediates recruitment of VAPA to plasma membrane sites (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:25447204). With OSBPL3, may regulate ER morphology (PubMed:16143324). May play a role in vesicle trafficking (PubMed:11511104, PubMed:19289470).4 Publications

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • FFAT motif binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB

GO - Biological processi

  • cell death Source: UniProtKB
  • COPII-coated vesicle budding Source: UniProtKB
  • ER to Golgi vesicle-mediated transport Source: UniProtKB
  • membrane fusion Source: ProtInc
  • negative regulation by host of viral genome replication Source: AgBase
  • neuron projection development Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • 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 I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • protein localization to endoplasmic reticulum Source: UniProtKB
  • sphingolipid biosynthetic process Source: Reactome

Enzyme and pathway databases

ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis
R-HSA-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
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 namesi
Name:VAPA
Synonyms:VAP33
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000101558.13
HGNCiHGNC:12648 VAPA
MIMi605703 gene
neXtProtiNX_Q9P0L0

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 – 227CytoplasmicSequence analysisAdd BLAST226
Transmembranei228 – 248Helical; Anchor for type IV membrane proteinSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell junction, Cell membrane, Endoplasmic reticulum, Membrane, Nucleus, Tight junction

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi94K → D: Alters interaction with ZFYVE27; when associated with D-96. 1 Publication1
Mutagenesisi96M → D: Alters interaction with ZFYVE27; when associated with D-94. 1 Publication1

Organism-specific databases

DisGeNETi9218
OpenTargetsiENSG00000101558
PharmGKBiPA37272

Polymorphism and mutation databases

BioMutaiVAPA
DMDMi122066680

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002134702 – 249Vesicle-associated membrane protein-associated protein AAdd BLAST248

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei125N6-acetyllysineCombined sources1
Modified residuei166PhosphoserineCombined sources1
Modified residuei170PhosphothreonineCombined sources1
Modified residuei214PhosphoserineCombined sources1
Modified residuei216PhosphoserineCombined sources1
Modified residuei219PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9P0L0
MaxQBiQ9P0L0
PeptideAtlasiQ9P0L0
PRIDEiQ9P0L0
ProteomicsDBi83567
83568 [Q9P0L0-2]
TopDownProteomicsiQ9P0L0-1 [Q9P0L0-1]
Q9P0L0-2 [Q9P0L0-2]

PTM databases

iPTMnetiQ9P0L0
PhosphoSitePlusiQ9P0L0
SwissPalmiQ9P0L0

Miscellaneous databases

PMAP-CutDBiQ9P0L0

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000101558
CleanExiHS_VAPA
ExpressionAtlasiQ9P0L0 baseline and differential
GenevisibleiQ9P0L0 HS

Organism-specific databases

HPAiHPA009174

Interactioni

Subunit structurei

Homodimer, and heterodimer with VAPB (PubMed:11511104). Interacts with VAMP1, VAMP2, STX1A, BET1, SEC22C and with the C-terminal domain of OCLN (PubMed:11511104, PubMed:9657962, PubMed:10523508). Interacts with OSBPL1A (By similarity). Interacts (via MSP domain) with ZFYVE27; may retain ZFYVE27 in the endoplasmic reticulum and regulate its function in cell projections formation (PubMed:19289470, PubMed:21976701). Interacts with OSBP (PubMed:20178991). Interacts (via C-terminus) with RSAD2/viperin (via C-terminus) (PubMed:21957124). Interacts with IFITM3 (PubMed:23601107). Interacts with OSBPL3 (phosphorylated form) (PubMed:16143324, PubMed:25447204). 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).By similarity11 Publications
(Microbial infection) Interacts with HCV protein NS5A and NS5B (PubMed:21957124).1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • FFAT motif binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi114651, 262 interactors
ComplexPortaliCPX-489 VAPA-OSBP complex
CORUMiQ9P0L0
DIPiDIP-41135N
IntActiQ9P0L0, 200 interactors
MINTiQ9P0L0

Structurei

Secondary structure

1249
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi14 – 21Combined sources8
Beta strandi23 – 27Combined sources5
Beta strandi33 – 40Combined sources8
Beta strandi43 – 45Combined sources3
Beta strandi47 – 54Combined sources8
Turni56 – 58Combined sources3
Beta strandi59 – 63Combined sources5
Beta strandi65 – 68Combined sources4
Beta strandi73 – 80Combined sources8
Beta strandi94 – 101Combined sources8
Helixi109 – 115Combined sources7
Turni118 – 120Combined sources3
Beta strandi122 – 131Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RR3NMR-A11-135[»]
ProteinModelPortaliQ9P0L0
SMRiQ9P0L0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9P0L0

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 131MSPPROSITE-ProRule annotationAdd BLAST118

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili169 – 205Sequence analysisAdd BLAST37

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00390000006947
HOGENOMiHOG000293182
HOVERGENiHBG028551
InParanoidiQ9P0L0
KOiK06096
OMAiTTQVEIC
OrthoDBiEOG091G0KJ2
PhylomeDBiQ9P0L0
TreeFamiTF317024

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR013783 Ig-like_fold
IPR000535 MSP_dom
IPR008962 PapD-like_sf
IPR016763 VAP
IPR030229 VAPA
PANTHERiPTHR10809 PTHR10809, 1 hit
PTHR10809:SF40 PTHR10809:SF40, 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: Q9P0L0-1) [UniParc]FASTAAdd to basket

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
MASASGAMAK HEQILVLDPP TDLKFKGPFT DVVTTNLKLR NPSDRKVCFK
60 70 80 90 100
VKTTAPRRYC VRPNSGIIDP GSTVTVSVML QPFDYDPNEK SKHKFMVQTI
110 120 130 140 150
FAPPNTSDME AVWKEAKPDE LMDSKLRCVF EMPNENDKLN DMEPSKAVPL
160 170 180 190 200
NASKQDGPMP KPHSVSLNDT ETRKLMEECK RLQGEMMKLS EENRHLRDEG
210 220 230 240
LRLRKVAHSD KPGSTSTASF RDNVTSPLPS LLVVIAAIFI GFFLGKFIL
Length:249
Mass (Da):27,893
Last modified:January 9, 2007 - v3
Checksum:i68B603F3A9FA5475
GO
Isoform 2 (identifier: Q9P0L0-2) [UniParc]FASTAAdd to basket

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

Show »
Length:294
Mass (Da):32,614
Checksum:i8B2D033706621878
GO

Sequence cautioni

The sequence AAD09742 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAF72105 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BG488667 differs from that shown. Reason: Frameshift at positions 72, 207 and 241.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10 – 11KH → ND in AAC26508 (PubMed:9657962).Curated2
Sequence conflicti10 – 11KH → ND in AAV38424 (Ref. 8) Curated2
Sequence conflicti160P → S in AAF72105 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0504408M → T. Corresponds to variant dbSNP:rs1044163Ensembl.1
Natural variantiVAR_050441104P → L. Corresponds to variant dbSNP:rs1127666Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038648139L → LGITPPGNAPTVTSMSSINN TVATPASYHTKDDPRGLSVL KQEKQK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS11847.2 [Q9P0L0-2]
CCDS11848.2 [Q9P0L0-1]
RefSeqiNP_003565.4, NM_003574.5 [Q9P0L0-2]
NP_919415.2, NM_194434.2 [Q9P0L0-1]
UniGeneiHs.165195

Genome annotation databases

EnsembliENST00000340541; ENSP00000345656; ENSG00000101558 [Q9P0L0-2]
ENST00000400000; ENSP00000382880; ENSG00000101558 [Q9P0L0-1]
GeneIDi9218
KEGGihsa:9218
UCSCiuc002koj.4 human [Q9P0L0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiVAPA_HUMAN
AccessioniPrimary (citable) accession number: Q9P0L0
Secondary accession number(s): A6NDZ0
, D3DUI3, O75453, Q5U0E7, Q9UBZ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: January 9, 2007
Last modified: June 20, 2018
This is version 174 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, Reference proteome

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