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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)DescriptionActionsGraphical viewLength
Sitei73Involved in hexokinase bindingBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi242 – 244NAD1 Publication3
Nucleotide bindingi260 – 264NAD1 Publication5

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

BioCyciZFISH:ENSG00000073905-MONOMER.
ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-5205685. Pink/Parkin Mediated Mitophagy.
R-HSA-5689880. Ub-specific processing proteases.
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)DescriptionActionsGraphical viewLength
Transmembranei26 – 35Beta stranded2 Publications10
Transmembranei39 – 47Beta stranded2 Publications9
Transmembranei54 – 64Beta stranded2 PublicationsAdd BLAST11
Transmembranei69 – 76Beta stranded2 Publications8
Transmembranei80 – 89Beta stranded2 Publications10
Transmembranei95 – 104Beta stranded2 Publications10
Transmembranei111 – 120Beta stranded2 Publications10
Transmembranei123 – 130Beta stranded2 Publications8
Transmembranei137 – 145Beta stranded2 Publications9
Transmembranei150 – 158Beta stranded2 Publications9
Transmembranei163 – 175Beta stranded2 PublicationsAdd BLAST13
Transmembranei178 – 185Beta stranded2 Publications8
Transmembranei189 – 198Beta stranded2 Publications10
Transmembranei202 – 211Beta stranded2 Publications10
Transmembranei218 – 227Beta stranded2 Publications10
Transmembranei231 – 238Beta stranded2 Publications8
Transmembranei242 – 251Beta stranded2 Publications10
Transmembranei254 – 263Beta stranded2 Publications10
Transmembranei273 – 282Beta stranded2 Publications10

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)DescriptionActionsGraphical viewLength
Mutagenesisi193S → A: Conformation remains open and constitutively allows cytochrome c efflux. 1 Publication1
Mutagenesisi193S → E: Conformation remains closed and prevents cytochrome c leakage. 1 Publication1

Organism-specific databases

DisGeNETi7416.
MIMi604492. gene+phenotype.
OpenTargetsiENSG00000213585.
PharmGKBiPA37292.

Chemistry databases

DrugBankiDB01375. Dihydroxyaluminium.

Polymorphism and mutation databases

BioMutaiVDAC1.
DMDMi130683.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources4 Publications
ChainiPRO_00000504992 – 283Voltage-dependent anion-selective channel protein 1Add BLAST282

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources2 Publications1
Modified residuei13PhosphoserineBy similarity1
Modified residuei19PhosphothreonineBy similarity1
Modified residuei20N6-acetyllysine; alternateCombined sources1
Modified residuei20N6-succinyllysine; alternateBy similarity1
Cross-linki53Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki61Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei67PhosphotyrosineBy similarity1
Modified residuei107PhosphothreonineCombined sources1
Modified residuei109N6-acetyllysine; alternateBy similarity1
Cross-linki109Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Cross-linki110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki161Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei193Phosphoserine; by NEK11 Publication1
Modified residuei240PhosphoserineCombined sources1
Modified residuei241PhosphoserineBy similarity1
Modified residuei252N6-acetyllysineBy similarity1
Modified residuei266N6-acetyllysine; alternateCombined sources1
Cross-linki266Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Cross-linki274Glycyl 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.
PhosphoSitePlusiP21796.
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 interactors.
DIPiDIP-32862N.
IntActiP21796. 45 interactors.
MINTiMINT-5002499.
STRINGi9606.ENSP00000265333.

Structurei

Secondary structure

1283
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni7 – 10Combined sources4
Helixi12 – 19Combined sources8
Beta strandi26 – 33Combined sources8
Turni36 – 38Combined sources3
Beta strandi40 – 51Combined sources12
Beta strandi55 – 62Combined sources8
Beta strandi66 – 76Combined sources11
Turni77 – 79Combined sources3
Beta strandi80 – 88Combined sources9
Beta strandi95 – 103Combined sources9
Turni105 – 107Combined sources3
Beta strandi110 – 119Combined sources10
Beta strandi124 – 135Combined sources12
Beta strandi137 – 146Combined sources10
Beta strandi149 – 158Combined sources10
Turni159 – 162Combined sources4
Beta strandi167 – 174Combined sources8
Beta strandi176 – 185Combined sources10
Turni186 – 188Combined sources3
Beta strandi189 – 196Combined sources8
Beta strandi203 – 211Combined sources9
Turni212 – 214Combined sources3
Beta strandi217 – 228Combined sources12
Beta strandi231 – 241Combined sources11
Beta strandi243 – 250Combined sources8
Beta strandi252 – 254Combined sources3
Beta strandi256 – 264Combined sources9
Helixi268 – 270Combined sources3
Beta strandi274 – 282Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JK4X-ray4.10A2-283[»]
2K4TNMR-A1-283[»]
5JDPNMR-A2-283[»]
ProteinModelPortaliP21796.
SMRiP21796.
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)DescriptionActionsGraphical viewLength
Sequence conflicti225Y → L in CAB58127 (PubMed:10772903).Curated1

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.
XP_016865310.1. XM_017009821.1.
XP_016865311.1. XM_017009822.1.
XP_016865312.1. XM_017009823.1.
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.
XP_016865310.1. XM_017009821.1.
XP_016865311.1. XM_017009822.1.
XP_016865312.1. XM_017009823.1.
UniGeneiHs.519320.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JK4X-ray4.10A2-283[»]
2K4TNMR-A1-283[»]
5JDPNMR-A2-283[»]
ProteinModelPortaliP21796.
SMRiP21796.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113259. 135 interactors.
DIPiDIP-32862N.
IntActiP21796. 45 interactors.
MINTiMINT-5002499.
STRINGi9606.ENSP00000265333.

Chemistry databases

DrugBankiDB01375. Dihydroxyaluminium.

PTM databases

iPTMnetiP21796.
PhosphoSitePlusiP21796.
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.
DisGeNETi7416.
GeneCardsiVDAC1.
H-InvDBHIX0056260.
HGNCiHGNC:12669. VDAC1.
HPAiCAB005885.
HPA030780.
MIMi604492. gene+phenotype.
neXtProtiNX_P21796.
OpenTargetsiENSG00000213585.
PharmGKBiPA37292.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073905-MONOMER.
ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-5205685. Pink/Parkin Mediated Mitophagy.
R-HSA-5689880. Ub-specific processing proteases.
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: November 30, 2016
This is version 190 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.