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Protein

Voltage-dependent anion-selective channel protein 1

Gene

VDAC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:11845315, PubMed:18755977, PubMed:20230784, PubMed:8420959). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756).6 Publications

Enzyme regulationi

Inhibited by nitric oxide.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei73 – 731Involved in hexokinase bindingBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi242 – 2443NAD1 Publication
Nucleotide bindingi260 – 2645NAD1 Publication

GO - Molecular functioni

  • ion channel binding Source: UniProtKB
  • porin activity Source: UniProtKB-KW
  • protein kinase binding Source: ParkinsonsUK-UCL
  • voltage-gated anion channel activity Source: UniProtKB

GO - Biological processi

  • anion transport Source: UniProtKB
  • apoptotic process Source: UniProtKB
  • behavioral fear response Source: Ensembl
  • epithelial cell differentiation Source: UniProtKB
  • learning Source: Ensembl
  • macroautophagy Source: Reactome
  • mitochondrial calcium ion transport Source: Ensembl
  • negative regulation of reactive oxygen species metabolic process Source: Ensembl
  • neuron-neuron synaptic transmission Source: Ensembl
  • regulation of mitophagy Source: ParkinsonsUK-UCL
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Porin

Keywords - Biological processi

Apoptosis, Host-virus interaction, Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-5205685. Pink/Parkin Mediated Mitophagy.
SIGNORiP21796.

Names & Taxonomyi

Protein namesi
Recommended name:
Voltage-dependent anion-selective channel protein 1
Short name:
VDAC-1
Short name:
hVDAC1
Alternative name(s):
Outer mitochondrial membrane protein porin 1
Plasmalemmal porin
Porin 31HL
Porin 31HM
Gene namesi
Name:VDAC1
Synonyms:VDAC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:12669. VDAC1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei26 – 3510Beta stranded2 Publications
Transmembranei39 – 479Beta stranded2 Publications
Transmembranei54 – 6411Beta stranded2 PublicationsAdd
BLAST
Transmembranei69 – 768Beta stranded2 Publications
Transmembranei80 – 8910Beta stranded2 Publications
Transmembranei95 – 10410Beta stranded2 Publications
Transmembranei111 – 12010Beta stranded2 Publications
Transmembranei123 – 1308Beta stranded2 Publications
Transmembranei137 – 1459Beta stranded2 Publications
Transmembranei150 – 1589Beta stranded2 Publications
Transmembranei163 – 17513Beta stranded2 PublicationsAdd
BLAST
Transmembranei178 – 1858Beta stranded2 Publications
Transmembranei189 – 19810Beta stranded2 Publications
Transmembranei202 – 21110Beta stranded2 Publications
Transmembranei218 – 22710Beta stranded2 Publications
Transmembranei231 – 2388Beta stranded2 Publications
Transmembranei242 – 25110Beta stranded2 Publications
Transmembranei254 – 26310Beta stranded2 Publications
Transmembranei273 – 28210Beta stranded2 Publications

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • membrane raft Source: UniProtKB-SubCell
  • mitochondrial inner membrane Source: Ensembl
  • mitochondrial nucleoid Source: BHF-UCL
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • myelin sheath Source: Ensembl
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • pore complex Source: HGNC
  • synaptic vesicle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi193 – 1931S → A: Conformation remains open and constitutively allows cytochrome c efflux. 1 Publication
Mutagenesisi193 – 1931S → E: Conformation remains closed and prevents cytochrome c leakage. 1 Publication

Organism-specific databases

MIMi604492. gene+phenotype.
PharmGKBiPA37292.

Chemistry

DrugBankiDB01375. Dihydroxyaluminium.

Polymorphism and mutation databases

BioMutaiVDAC1.
DMDMi130683.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources4 Publications
Chaini2 – 283282Voltage-dependent anion-selective channel protein 1PRO_0000050499Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources2 Publications
Modified residuei13 – 131PhosphoserineBy similarity
Modified residuei19 – 191PhosphothreonineBy similarity
Modified residuei20 – 201N6-acetyllysine; alternateCombined sources
Modified residuei20 – 201N6-succinyllysine; alternateBy similarity
Cross-linki53 – 53Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki61 – 61Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei67 – 671PhosphotyrosineBy similarity
Modified residuei107 – 1071PhosphothreonineCombined sources
Modified residuei109 – 1091N6-acetyllysine; alternateBy similarity
Cross-linki109 – 109Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Cross-linki110 – 110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki161 – 161Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei193 – 1931Phosphoserine; by NEK11 Publication
Modified residuei240 – 2401PhosphoserineCombined sources
Modified residuei252 – 2521N6-acetyllysineBy similarity
Modified residuei266 – 2661N6-acetyllysine; alternateCombined sources
Cross-linki266 – 266Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Cross-linki274 – 274Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Phosphorylation at Ser-193 by NEK1 promotes the open conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury. Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation.1 Publication
Ubiquitinated by PARK2 during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP21796.
MaxQBiP21796.
PaxDbiP21796.
PeptideAtlasiP21796.
PRIDEiP21796.
TopDownProteomicsiP21796.

2D gel databases

DOSAC-COBS-2DPAGEP21796.
OGPiP21796.
REPRODUCTION-2DPAGEIPI00216308.
P21796.
UCD-2DPAGEP21796.

PTM databases

iPTMnetiP21796.
PhosphoSiteiP21796.
SwissPalmiP21796.

Expressioni

Tissue specificityi

Heart, liver and skeletal muscle.

Gene expression databases

BgeeiENSG00000213585.
CleanExiHS_VDAC1.
ExpressionAtlasiP21796. baseline and differential.
GenevisibleiP21796. HS.

Organism-specific databases

HPAiCAB005885.
HPA030780.

Interactioni

Subunit structurei

Interacts with hexokinases including HK1 (PubMed:8420959, PubMed:22304920). The HK1-VDAC1 complex interacts with ATF2 (PubMed:22304920). Interacts with BCL2L1 (PubMed:18755977, PubMed:25296756). Interacts with BAK1 (PubMed:25296756). Interacts with BOP/C22orf29 (via BH3 domain) (PubMed:23055042). Interacts with beta amyloid and APP; induces VDAC1 dephosphorylation (PubMed:25168729).6 Publications
(Microbial infection) Interacts with influenza A virus PB1-F2 protein.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
BOPQ7L3V22EBI-354158,EBI-10697720
HK1P193672EBI-354158,EBI-713162
ITPR1Q146433EBI-354158,EBI-465548

GO - Molecular functioni

  • ion channel binding Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi113259. 135 interactions.
DIPiDIP-32862N.
IntActiP21796. 43 interactions.
MINTiMINT-5002499.
STRINGi9606.ENSP00000265333.

Structurei

Secondary structure

1
283
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni7 – 104Combined sources
Beta strandi26 – 338Combined sources
Turni36 – 383Combined sources
Beta strandi40 – 5112Combined sources
Beta strandi55 – 628Combined sources
Beta strandi66 – 7611Combined sources
Turni77 – 793Combined sources
Beta strandi80 – 889Combined sources
Beta strandi95 – 1039Combined sources
Turni105 – 1073Combined sources
Beta strandi110 – 11910Combined sources
Beta strandi124 – 13512Combined sources
Beta strandi137 – 14610Combined sources
Beta strandi149 – 15810Combined sources
Turni159 – 1624Combined sources
Beta strandi167 – 1748Combined sources
Beta strandi176 – 18510Combined sources
Turni186 – 1883Combined sources
Beta strandi189 – 1968Combined sources
Beta strandi203 – 2119Combined sources
Beta strandi217 – 22812Combined sources
Beta strandi231 – 24111Combined sources
Beta strandi243 – 2508Combined sources
Beta strandi252 – 2543Combined sources
Beta strandi256 – 2649Combined sources
Helixi268 – 2703Combined sources
Beta strandi274 – 2829Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JK4X-ray4.10A2-283[»]
2K4TNMR-A1-283[»]
ProteinModelPortaliP21796.
SMRiP21796. Positions 2-283.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21796.

Family & Domainsi

Domaini

Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands. The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity.

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane beta strand

Phylogenomic databases

eggNOGiKOG3126. Eukaryota.
ENOG410ZBK1. LUCA.
GeneTreeiENSGT00390000011336.
HOGENOMiHOG000188277.
HOVERGENiHBG054036.
InParanoidiP21796.
KOiK05862.
OMAiYGLMFTE.
OrthoDBiEOG091G0F0O.
PhylomeDBiP21796.
TreeFamiTF315091.

Family and domain databases

Gene3Di2.40.160.10. 1 hit.
InterProiIPR023614. Porin_dom.
IPR001925. Porin_Euk.
IPR027246. Porin_Euk/Tom40.
IPR030270. VDAC1.
[Graphical view]
PANTHERiPTHR11743:SF13. PTHR11743:SF13. 1 hit.
PfamiPF01459. Porin_3. 1 hit.
[Graphical view]
PRINTSiPR00185. EUKARYTPORIN.
PROSITEiPS00558. EUKARYOTIC_PORIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P21796-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVPPTYADL GKSARDVFTK GYGFGLIKLD LKTKSENGLE FTSSGSANTE
60 70 80 90 100
TTKVTGSLET KYRWTEYGLT FTEKWNTDNT LGTEITVEDQ LARGLKLTFD
110 120 130 140 150
SSFSPNTGKK NAKIKTGYKR EHINLGCDMD FDIAGPSIRG ALVLGYEGWL
160 170 180 190 200
AGYQMNFETA KSRVTQSNFA VGYKTDEFQL HTNVNDGTEF GGSIYQKVNK
210 220 230 240 250
KLETAVNLAW TAGNSNTRFG IAAKYQIDPD ACFSAKVNNS SLIGLGYTQT
260 270 280
LKPGIKLTLS ALLDGKNVNA GGHKLGLGLE FQA
Length:283
Mass (Da):30,773
Last modified:January 23, 2007 - v2
Checksum:i89BA3378B04020D5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti225 – 2251Y → L in CAB58127 (PubMed:10772903).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06132 mRNA. Translation: AAA61272.1.
AJ250032
, AJ250033, AJ250034, AJ250035, AJ250036, AJ250037, AJ250038, AJ250039 Genomic DNA. Translation: CAB58127.1.
AF151097
, AF151093, AF151094, AF151095, AF151096 Genomic DNA. Translation: AAD54939.1.
AC005200 Genomic DNA. Translation: AAC24723.1.
AK122953 mRNA. Translation: BAG53816.1.
AC008608 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW62281.1.
CH471062 Genomic DNA. Translation: EAW62282.1.
CH471062 Genomic DNA. Translation: EAW62283.1.
CH471062 Genomic DNA. Translation: EAW62285.1.
CH471062 Genomic DNA. Translation: EAW62286.1.
BC008482 mRNA. Translation: AAH08482.1.
BC071168 mRNA. Translation: AAH71168.1.
BC090042 mRNA. Translation: AAH90042.1.
CCDSiCCDS4168.1.
PIRiA44422. MMHUP3.
RefSeqiNP_003365.1. NM_003374.2.
XP_005272132.1. XM_005272075.3.
UniGeneiHs.519320.

Genome annotation databases

EnsembliENST00000265333; ENSP00000265333; ENSG00000213585.
ENST00000395044; ENSP00000378484; ENSG00000213585.
ENST00000395047; ENSP00000378487; ENSG00000213585.
GeneIDi7416.
KEGGihsa:7416.
UCSCiuc003kyp.3. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06132 mRNA. Translation: AAA61272.1.
AJ250032
, AJ250033, AJ250034, AJ250035, AJ250036, AJ250037, AJ250038, AJ250039 Genomic DNA. Translation: CAB58127.1.
AF151097
, AF151093, AF151094, AF151095, AF151096 Genomic DNA. Translation: AAD54939.1.
AC005200 Genomic DNA. Translation: AAC24723.1.
AK122953 mRNA. Translation: BAG53816.1.
AC008608 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW62281.1.
CH471062 Genomic DNA. Translation: EAW62282.1.
CH471062 Genomic DNA. Translation: EAW62283.1.
CH471062 Genomic DNA. Translation: EAW62285.1.
CH471062 Genomic DNA. Translation: EAW62286.1.
BC008482 mRNA. Translation: AAH08482.1.
BC071168 mRNA. Translation: AAH71168.1.
BC090042 mRNA. Translation: AAH90042.1.
CCDSiCCDS4168.1.
PIRiA44422. MMHUP3.
RefSeqiNP_003365.1. NM_003374.2.
XP_005272132.1. XM_005272075.3.
UniGeneiHs.519320.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JK4X-ray4.10A2-283[»]
2K4TNMR-A1-283[»]
ProteinModelPortaliP21796.
SMRiP21796. Positions 2-283.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113259. 135 interactions.
DIPiDIP-32862N.
IntActiP21796. 43 interactions.
MINTiMINT-5002499.
STRINGi9606.ENSP00000265333.

Chemistry

DrugBankiDB01375. Dihydroxyaluminium.

PTM databases

iPTMnetiP21796.
PhosphoSiteiP21796.
SwissPalmiP21796.

Polymorphism and mutation databases

BioMutaiVDAC1.
DMDMi130683.

2D gel databases

DOSAC-COBS-2DPAGEP21796.
OGPiP21796.
REPRODUCTION-2DPAGEIPI00216308.
P21796.
UCD-2DPAGEP21796.

Proteomic databases

EPDiP21796.
MaxQBiP21796.
PaxDbiP21796.
PeptideAtlasiP21796.
PRIDEiP21796.
TopDownProteomicsiP21796.

Protocols and materials databases

DNASUi7416.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265333; ENSP00000265333; ENSG00000213585.
ENST00000395044; ENSP00000378484; ENSG00000213585.
ENST00000395047; ENSP00000378487; ENSG00000213585.
GeneIDi7416.
KEGGihsa:7416.
UCSCiuc003kyp.3. human.

Organism-specific databases

CTDi7416.
GeneCardsiVDAC1.
H-InvDBHIX0056260.
HGNCiHGNC:12669. VDAC1.
HPAiCAB005885.
HPA030780.
MIMi604492. gene+phenotype.
neXtProtiNX_P21796.
PharmGKBiPA37292.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3126. Eukaryota.
ENOG410ZBK1. LUCA.
GeneTreeiENSGT00390000011336.
HOGENOMiHOG000188277.
HOVERGENiHBG054036.
InParanoidiP21796.
KOiK05862.
OMAiYGLMFTE.
OrthoDBiEOG091G0F0O.
PhylomeDBiP21796.
TreeFamiTF315091.

Enzyme and pathway databases

ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-5205685. Pink/Parkin Mediated Mitophagy.
SIGNORiP21796.

Miscellaneous databases

ChiTaRSiVDAC1. human.
EvolutionaryTraceiP21796.
GeneWikiiVDAC1.
GenomeRNAii7416.
PROiP21796.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213585.
CleanExiHS_VDAC1.
ExpressionAtlasiP21796. baseline and differential.
GenevisibleiP21796. HS.

Family and domain databases

Gene3Di2.40.160.10. 1 hit.
InterProiIPR023614. Porin_dom.
IPR001925. Porin_Euk.
IPR027246. Porin_Euk/Tom40.
IPR030270. VDAC1.
[Graphical view]
PANTHERiPTHR11743:SF13. PTHR11743:SF13. 1 hit.
PfamiPF01459. Porin_3. 1 hit.
[Graphical view]
PRINTSiPR00185. EUKARYTPORIN.
PROSITEiPS00558. EUKARYOTIC_PORIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVDAC1_HUMAN
AccessioniPrimary (citable) accession number: P21796
Secondary accession number(s): B3KVK4
, D3DQ93, Q5FVE7, Q9UIQ5, Q9UPL0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 187 of the entry and version 2 of the sequence. [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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.