Reactome | UniProt:P21796 VDAC1

Schema > ReferenceGeneProduct > Entries

UniProt:P21796 VDAC1 Show undefined attributes

chain	initiator methionine:1 chain:2-283
checksum	89BA3378B04020D5
comment	FUNCTION Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:30061676, PubMed:8420959). 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 (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:8420959). It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (PubMed:10661876, PubMed:18755977, PubMed:8420959). The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:18755977, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:18755977, PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). 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). May mediate ATP export from cells (PubMed:30061676). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Mediates cytochrome c efflux (PubMed:20230784).FUNCTION Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids.CATALYTIC ACTIVITY chloride(in) = chloride(out)CATALYTIC ACTIVITY K(+)(in) = K(+)(out)CATALYTIC ACTIVITY ATP(in) = ATP(out)CATALYTIC ACTIVITY Ca(2+)(in) = Ca(2+)(out)CATALYTIC ACTIVITY Na(+)(in) = Na(+)(out)CATALYTIC ACTIVITY Mg(2+)(in) = Mg(2+)(out)CATALYTIC ACTIVITY L-glutamate(out) = L-glutamate(in)CATALYTIC ACTIVITY dopamine(out) = dopamine(in)CATALYTIC ACTIVITY acetylcholine(in) = acetylcholine(out)CATALYTIC ACTIVITY Fe(III)-[cytochrome c](out) = Fe(III)-[cytochrome c](in)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out)ACTIVITY REGULATION Inhibited by nitric oxide.SUBUNIT Homodimer and homotrimer; in response to cyclic AMP or calcium; oligomerization is required for scramblase activity (PubMed:30061676, PubMed:38065946). 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). Interacts with hexokinases including HK1 (PubMed:22304920, PubMed:8420959). 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). Interacts with TMEM41B (PubMed:30352685). Interacts with BCAP31 (PubMed:31206022). Interacts with HSPA9; this interaction couples ITPR1 to VDAC1 (By similarity).SUBUNIT (Microbial infection) Interacts with influenza A virus PB1-F2 protein.INTERACTION Found in a complex with HSPA9 and VDAC1 at the endoplasmic reticulum-mitochondria contact sites.TISSUE SPECIFICITY Expressed in erythrocytes (at protein level) (PubMed:27641616). Expressed in heart, liver and skeletal muscle (PubMed:8420959).DOMAIN Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands (PubMed:18755977, PubMed:18832158). The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity (PubMed:18755977, PubMed:18832158).PTM Phosphorylation at Ser-193 by NEK1 promotes the closed conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury (PubMed:20230784). Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation.PTM Ubiquitinated (PubMed:25621951, PubMed:32047033). Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy (PubMed:25621951, PubMed:32047033). Deubiquitinated by USP30 (PubMed:25621951).SIMILARITY Belongs to the eukaryotic mitochondrial porin family.
crossReference	[DatabaseIdentifier:11645420] ENSEMBL:ENSP00000378484 [DatabaseIdentifier:12478976] RefSeq:NP_001387946.1 [DatabaseIdentifier:12478986] RefSeq:NP_001387951.1 [DatabaseIdentifier:12478983] RefSeq:NP_001387950.1 [DatabaseIdentifier:12478982] RefSeq:NP_003365.1 [DatabaseIdentifier:12478979] RefSeq:NP_001387938.1 [DatabaseIdentifier:12478981] RefSeq:NP_001387939.1 [DatabaseIdentifier:12478987] RefSeq:NP_001387945.1 [DatabaseIdentifier:12478980] RefSeq:NP_001387949.1 [DatabaseIdentifier:12478985] RefSeq:NP_001387952.1 [DatabaseIdentifier:12478977] RefSeq:NP_001387947.1 [DatabaseIdentifier:12478984] RefSeq:NP_001387940.1 [DatabaseIdentifier:12478978] RefSeq:NP_001387937.1 [DatabaseIdentifier:12292465] Pharos - Targets:P21796 [DatabaseIdentifier:12275515] PRO:P21796 [DatabaseIdentifier:12223570] PDB:5XDN [DatabaseIdentifier:12223578] PDB:6TIR [DatabaseIdentifier:12223574] PDB:5JDP [DatabaseIdentifier:12223572] PDB:2JK4 [DatabaseIdentifier:12223575] PDB:6G6U [DatabaseIdentifier:12223573] PDB:5XDO [DatabaseIdentifier:12223576] PDB:7QI2 [DatabaseIdentifier:12223577] PDB:2K4T [DatabaseIdentifier:12223579] PDB:6TIQ [DatabaseIdentifier:12140868] PDB:8J0O [DatabaseIdentifier:12223571] PDB:6G73 [DatabaseIdentifier:12132294] OpenTargets:ENSG00000213585 [DatabaseIdentifier:11847612] HPA:ENSG00000213585-VDAC1 [DatabaseIdentifier:11831758] HMDB Protein:HMDBP02507 [DatabaseIdentifier:11810602] GlyGen:P21796 [DatabaseIdentifier:11794642] GeneCards:VDAC1 [DatabaseIdentifier:11768119] ENSEMBL:ENST00000395044 [DatabaseIdentifier:11768118] ENSEMBL:ENST00000265333 [DatabaseIdentifier:11768117] ENSEMBL:ENST00000395047 [DatabaseIdentifier:11645419] ENSEMBL:ENSP00000265333 [DatabaseIdentifier:11645418] ENSEMBL:ENSP00000378487 [DatabaseIdentifier:11524327] ENSEMBL:ENSG00000213585
databaseName	UniProt
dbId	61986
description	recommendedName: fullName evidence="32"Non-selective voltage-gated ion channel VDAC1 alternativeName: Outer mitochondrial membrane protein porin 1 alternativeName: Plasmalemmal porin alternativeName: Porin 31HL alternativeName: Porin 31HM alternativeName: Voltage-dependent anion-selective channel protein 1 shortName: VDAC-1 shortName: hVDAC1
displayName	UniProt:P21796 VDAC1
geneName	VDAC1 VDAC
identifier	P21796
isSequenceChanged	false
keyword	3D-structure Acetylation Apoptosis ATP-binding Cell membrane Direct protein sequencing Host-virus interaction Ion transport Isopeptide bond Lipid transport Lipid-binding Membrane Mitochondrion Mitochondrion outer membrane NAD Nucleotide-binding Phosphoprotein Porin Proteomics identification Reference proteome Transmembrane Transmembrane beta strand Transport Ubl conjugation
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	VDAC1
otherIdentifier	11715655_s_at 16999985 212038_PM_s_at 212038_s_at 217140_PM_s_at 217140_s_at 2370085 2683588 2875898 2875902 2875903 2875904 2875955 2875956 2875957 2875958 2875959 2875960 2875961 2875962 2875963 2875964 2875965 2875966 2875967 2875968 2875972 2875974 2875978 2875980 2875982 31608_g_at 3456919 3982776 3982780 3982781 4008064 4008066 4008075 4008077 4014643 40198_at 4033601 49354_at 7416 8114145 A_23_P144816 GE57563 GE84736 GO:0000166 GO:0001662 GO:0005244 GO:0005515 GO:0005524 GO:0005634 GO:0005739 GO:0005741 GO:0005757 GO:0005886 GO:0006811 GO:0006820 GO:0006869 GO:0006915 GO:0007268 GO:0007270 GO:0007612 GO:0008142 GO:0008289 GO:0008308 GO:0015288 GO:0015485 GO:0016020 GO:0019901 GO:0030154 GO:0030855 GO:0031210 GO:0031966 GO:0036444 GO:0042645 GO:0042802 GO:0043065 GO:0043066 GO:0044325 GO:0045121 GO:0045202 GO:0046930 GO:0050877 GO:0055085 GO:0070062 GO:0097001 GO:0098656 GO:0110099 GO:1901524 GO:1903146 GO:1905091 GO:1990542 GO:2000378 HMNXSV003020379 Hs.149155.2.A1_3p_a_at ILMN_2175601 L06132_at PH_hs_0030040 TC05001785.hg TC05003242.hg p33706
physicalEntity	[EntityWithAccessionedSequence:R-HSA-9834991] p-S65-Ub:VDAC1 [mitochondrial outer membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9834037] K63polyUb-VDAC1 [mitochondrial outer membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5205624] K48polyUb-VDAC1 [mitochondrial outer membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9834989] Ub-VDAC1 [mitochondrial outer membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1267988] VDAC1 [mitochondrial outer membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1267960] VDAC1 [mitochondrial intermembrane space] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6783079] PolyUb-VDAC1 [mitochondrial outer membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000213585] ENSEMBL:ENSG00000213585 VDAC1 [ReferenceDNASequence:12770067] UCSC:P21796 VDAC1 [ReferenceDNASequence:12116667] OMIM:604492 VDAC1 [ReferenceDNASequence:12102047] NCBI Gene:7416 VDAC1 [ReferenceDNASequence:12017954] Monarch:7416 VDAC1 [ReferenceDNASequence:11924543] KEGG:hsa:7416 VDAC1 [ReferenceDNASequence:11826338] HGNC:12669 VDAC1 [ReferenceDNASequence:11388165] BioGPS Gene:7416 VDAC1 [ReferenceDNASequence:11404128] COSMIC - genes:VDAC1 VDAC1 [ReferenceDNASequence:11423446] CTD Gene:7416 VDAC1 [ReferenceDNASequence:11441798] dbSNP Gene:7416 VDAC1
referenceTranscript	[ReferenceRNASequence:12660481] RefSeq:NM_001401022.1 VDAC1 [ReferenceRNASequence:12660483] RefSeq:NM_001401010.1 VDAC1 [ReferenceRNASequence:12660482] RefSeq:NM_001401011.1 VDAC1 [ReferenceRNASequence:12660480] RefSeq:NM_001401021.1 VDAC1 [ReferenceRNASequence:12660479] RefSeq:NM_001401009.1 VDAC1 [ReferenceRNASequence:12660485] RefSeq:NM_001401023.1 VDAC1 [ReferenceRNASequence:12660490] RefSeq:NM_003374.3 VDAC1 [ReferenceRNASequence:12660487] RefSeq:NM_001401016.1 VDAC1 [ReferenceRNASequence:12660484] RefSeq:NM_001401020.1 VDAC1 [ReferenceRNASequence:12660488] RefSeq:NM_001401008.1 VDAC1 [ReferenceRNASequence:12660486] RefSeq:NM_001401017.1 VDAC1 [ReferenceRNASequence:12660489] RefSeq:NM_001401018.1 VDAC1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	VDAC1_HUMAN B3KVK4 D3DQ93 Q5FVE7 Q9UIQ5 Q9UPL0
sequenceLength	283
species	[Species:48887] Homo sapiens
stId	uniprot:P21796
url	http://purl.uniprot.org/uniprot/P21796

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-9834991] p-S65-Ub:VDAC1 [mitochondrial outer membrane] [EntityWithAccessionedSequence:R-HSA-9834037] K63polyUb-VDAC1 [mitochondrial outer membrane] [EntityWithAccessionedSequence:R-HSA-5205624] K48polyUb-VDAC1 [mitochondrial outer membrane] [EntityWithAccessionedSequence:R-HSA-9834989] Ub-VDAC1 [mitochondrial outer membrane] [EntityWithAccessionedSequence:R-HSA-1267988] VDAC1 [mitochondrial outer membrane] [EntityWithAccessionedSequence:R-HSA-1267960] VDAC1 [mitochondrial intermembrane space] [EntityWithAccessionedSequence:R-HSA-6783079] PolyUb-VDAC1 [mitochondrial outer membrane]
(referenceSequence)	[GroupModifiedResidue:9834992] ubiquitinylated lysine (p-S65-Ub [mitochondrial outer membrane]) at unknown position [GroupModifiedResidue:9834041] ubiquitinylated lysine (K63polyUb [cytosol]) at unknown position [GroupModifiedResidue:5205665] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position [GroupModifiedResidue:9834997] ubiquitinylated lysine (Ub [mitochondrial outer membrane]) at unknown position [GroupModifiedResidue:6783006] ubiquitinylated lysine (PolyUb [mitochondrial outer membrane]) at unknown position
(interactor)	[UndirectedInteraction:11133575] UniProt:P12236 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11149377] UniProt:P13569 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11151337] UniProt:Q07813 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11154885] UniProt:P02649 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11165253] UniProt:P19367 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11193041] UniProt:P06493 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11237145] UniProt:P21796 <-> UniProt:Q9Y277 (IntAct) [UndirectedInteraction:11237147] UniProt:P21796 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11237147] UniProt:P21796 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11237149] UniProt:P21796 <-> UniProt:P45880 (IntAct) [UndirectedInteraction:11237151] UniProt:P21796 <-> UniProt:P0C0U1 (IntAct) [UndirectedInteraction:11237153] UniProt:P21796 <-> UniProt:P15336 (IntAct) [UndirectedInteraction:11237155] UniProt:P21796 <-> UniProt:Q5S007 (IntAct) [UndirectedInteraction:11237157] UniProt:P21796 <-> UniProt:P06753 (IntAct) [UndirectedInteraction:11237159] UniProt:P21796 <-> UniProt:P81605 (IntAct) [UndirectedInteraction:11237161] UniProt:P21796 <-> UniProt:Q16611 (IntAct) [UndirectedInteraction:11237165] UniProt:P21796 <-> UniProt:Q7L3V2 (IntAct) [UndirectedInteraction:11237167] UniProt:P21796 <-> UniProt:P27824 (IntAct) [UndirectedInteraction:11237169] UniProt:P21796 <-> UniProt:P0DTD1-PRO_0000449624 (IntAct) [UndirectedInteraction:11237171] UniProt:P21796 <-> UniProt:P61019 (IntAct) [UndirectedInteraction:11237173] UniProt:P21796 <-> UniProt:P19320 (IntAct) [UndirectedInteraction:11237175] UniProt:P21796 <-> UniProt:P51149 (IntAct) [UndirectedInteraction:11237177] UniProt:P21796 <-> UniProt:P27105 (IntAct) [UndirectedInteraction:11237179] UniProt:P21796 <-> UniProt:P62258 (IntAct) [UndirectedInteraction:11237181] UniProt:P21796 <-> UniProt:P30041 (IntAct) [UndirectedInteraction:11237183] UniProt:P21796 <-> UniProt:Q9H9B4 (IntAct) [UndirectedInteraction:11237185] UniProt:P21796 <-> UniProt:Q9NR30 (IntAct) [UndirectedInteraction:11237187] UniProt:P21796 <-> UniProt:P12956 (IntAct) [UndirectedInteraction:11237189] UniProt:P21796 <-> UniProt:P04578-PRO_0000038428 (IntAct)