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Protein

Voltage-dependent anion-selective channel protein 1

Gene

VDAC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • epithelial cell differentiation Source: UniProtKB
  • macroautophagy Source: Reactome
  • regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionPorin
Biological processApoptosis, Host-virus interaction, Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1268020 Mitochondrial protein import
R-HSA-5205685 Pink/Parkin Mediated Mitophagy
R-HSA-5689880 Ub-specific processing proteases
R-HSA-8949215 Mitochondrial calcium ion transport
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

EuPathDBiHostDB:ENSG00000213585.10
HGNCiHGNC:12669 VDAC1
MIMi604492 gene+phenotype
neXtProtiNX_P21796

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
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

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 Aluminium monostearate

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-linki20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
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 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 PRKN 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-2DPAGEiP21796
OGPiP21796
REPRODUCTION-2DPAGEiIPI00216308
P21796
UCD-2DPAGEiP21796

PTM databases

CarbonylDBiP21796
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 RTL10/BOP (via BH3 domain) (PubMed:23055042). Interacts with amyloid-beta and APP; induces VDAC1 dephosphorylation (PubMed:25168729). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with SPG7, NIPSNAP2 and SLC25A30 (PubMed:26387735).7 Publications
(Microbial infection) Interacts with influenza A virus PB1-F2 protein.1 Publication

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi113259, 279 interactors
CORUMiP21796
DIPiDIP-32862N
MINTiP21796
STRINGi9606.ENSP00000265333

Structurei

Secondary structure

1283
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni7 – 11Combined sources5
Helixi12 – 19Combined sources8
Turni20 – 22Combined sources3
Beta strandi25 – 33Combined sources9
Beta strandi36 – 38Combined sources3
Beta strandi40 – 51Combined sources12
Beta strandi54 – 63Combined sources10
Turni65 – 67Combined sources3
Beta strandi69 – 76Combined sources8
Beta strandi77 – 79Combined sources3
Beta strandi81 – 89Combined sources9
Turni92 – 94Combined sources3
Beta strandi95 – 103Combined sources9
Beta strandi105 – 107Combined sources3
Beta strandi112 – 119Combined sources8
Beta strandi121 – 130Combined sources10
Beta strandi132 – 134Combined sources3
Beta strandi137 – 146Combined sources10
Beta strandi149 – 158Combined sources10
Turni159 – 162Combined sources4
Beta strandi163 – 174Combined sources12
Beta strandi176 – 185Combined sources10
Turni186 – 188Combined sources3
Beta strandi189 – 199Combined sources11
Beta strandi202 – 211Combined sources10
Turni212 – 214Combined sources3
Beta strandi215 – 228Combined sources14
Beta strandi231 – 238Combined sources8
Turni239 – 241Combined sources3
Beta strandi242 – 252Combined sources11
Beta strandi255 – 266Combined sources12
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[»]
5XDNX-ray3.15A/B1-283[»]
5XDOX-ray3.10A/B1-283[»]
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
OMAiKYKWAEH
OrthoDBiEOG091G0F0O
PhylomeDBiP21796
TreeFamiTF315091

Family and domain databases

Gene3Di2.40.160.10, 1 hit
InterProiView protein in InterPro
IPR023614 Porin_dom_sf
IPR001925 Porin_Euk
IPR027246 Porin_Euk/Tom40
IPR030270 VDAC1
PANTHERiPTHR11743:SF13 PTHR11743:SF13, 1 hit
PfamiView protein in Pfam
PF01459 Porin_3, 1 hit
PRINTSiPR00185 EUKARYTPORIN
PROSITEiView protein in PROSITE
PS00558 EUKARYOTIC_PORIN, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiVDAC1_HUMAN
AccessioniPrimary (citable) accession number: P21796
Secondary accession number(s): B3KVK4
, D3DQ93, Q5FVE7, Q9UIQ5, Q9UPL0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 204 of the entry and version 2 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, 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

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