ID VDAC3_HUMAN Reviewed; 283 AA.
AC Q9Y277; Q9UIS0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-MAR-2024, entry version 199.
DE RecName: Full=Voltage-dependent anion-selective channel protein 3;
DE Short=VDAC-3;
DE Short=hVDAC3;
DE AltName: Full=Outer mitochondrial membrane protein porin 3;
GN Name=VDAC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=9781040; DOI=10.1038/sj.ejhg.5200198;
RA Rahmani Z., Maunoury C., Siddiqui A.;
RT "Isolation of a novel human voltage-dependent anion channel gene.";
RL Eur. J. Hum. Genet. 6:337-340(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-length
RT cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-253.
RX PubMed=10501981; DOI=10.1007/s003359901158;
RA Decker W.K., Bowles K.R., Schatte E.C., Towbin J.A., Craigen W.J.;
RT "Revised fine mapping of the human voltage-dependent anion channel loci by
RT radiation hybrid analysis.";
RL Mamm. Genome 10:1041-1042(1999).
RN [5]
RP ALTERNATIVE SPLICING.
RX PubMed=10833333; DOI=10.1006/mgme.2000.2987;
RA Decker W.K., Craigen W.J.;
RT "The tissue-specific, alternatively spliced single ATG exon of the type 3
RT voltage-dependent anion channel gene does not create a truncated protein
RT isoform in vivo.";
RL Mol. Genet. Metab. 70:69-74(2000).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT CYS-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-20 AND LYS-90, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-4, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP UBIQUITINATION AT LYS-53; LYS-61; LYS-109; LYS-110; LYS-163; LYS-266 AND
RP LYS-274.
RX PubMed=25621951; DOI=10.1038/ncb3097;
RA Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M.,
RA Kirkpatrick D.S., Bingol B., Corn J.E.;
RT "USP30 and parkin homeostatically regulate atypical ubiquitin chains on
RT mitochondria.";
RL Nat. Cell Biol. 17:160-169(2015).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT CYS-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=27641616; DOI=10.1038/srep33516;
RA Marginedas-Freixa I., Hattab C., Bouyer G., Halle F., Chene A.,
RA Lefevre S.D., Cambot M., Cueff A., Schmitt M., Gamain B., Lacapere J.J.,
RA Egee S., Bihel F., Le Van Kim C., Ostuni M.A.;
RT "TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to
RT the inhibition of P. falciparum growth in human blood.";
RL Sci. Rep. 6:33516-33516(2016).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane that
CC allows diffusion of small hydrophilic molecules (By similarity).
CC Involved in male fertility and sperm mitochondrial sheath formation (By
CC similarity). {ECO:0000250|UniProtKB:P21796,
CC ECO:0000250|UniProtKB:Q60931}.
CC -!- SUBUNIT: Interacts with ARMC12 in a TBC1D21-dependent manner. Interacts
CC with MISFA. {ECO:0000250|UniProtKB:Q60931}.
CC -!- INTERACTION:
CC Q9Y277; P21796: VDAC1; NbExp=2; IntAct=EBI-354196, EBI-354158;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P21796}. Membrane {ECO:0000269|PubMed:27641616}.
CC Note=May localize to non-mitochondrial membranes.
CC {ECO:0000269|PubMed:27641616}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y277-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y277-2; Sequence=VSP_005079;
CC -!- TISSUE SPECIFICITY: Expressed in erythrocytes (at protein level)
CC (PubMed:27641616). Widely expressed. Highest in testis
CC (PubMed:9781040). {ECO:0000269|PubMed:27641616,
CC ECO:0000269|PubMed:9781040}.
CC -!- DOMAIN: Consists mainly of a membrane-spanning beta-barrel formed by 19
CC beta-strands. {ECO:0000250|UniProtKB:P21796}.
CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation
CC and enhancement of mitophagy. Deubiquitinated by USP30.
CC {ECO:0000269|PubMed:25621951}.
CC -!- SIMILARITY: Belongs to the eukaryotic mitochondrial porin family.
CC {ECO:0000305}.
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DR EMBL; U90943; AAB93872.1; -; mRNA.
DR EMBL; AF038962; AAC39876.1; -; mRNA.
DR EMBL; BC056870; AAH56870.1; -; mRNA.
DR EMBL; AH008073; AAD49610.1; -; Genomic_DNA.
DR CCDS; CCDS47850.1; -. [Q9Y277-2]
DR CCDS; CCDS6131.1; -. [Q9Y277-1]
DR RefSeq; NP_001129166.1; NM_001135694.2. [Q9Y277-2]
DR RefSeq; NP_005653.3; NM_005662.6. [Q9Y277-1]
DR AlphaFoldDB; Q9Y277; -.
DR SMR; Q9Y277; -.
DR BioGRID; 113262; 330.
DR IntAct; Q9Y277; 65.
DR MINT; Q9Y277; -.
DR STRING; 9606.ENSP00000428845; -.
DR ChEMBL; CHEMBL4523505; -.
DR DrugBank; DB01375; Aluminium monostearate.
DR DrugBank; DB06098; PRLX 93936.
DR GlyGen; Q9Y277; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y277; -.
DR PhosphoSitePlus; Q9Y277; -.
DR SwissPalm; Q9Y277; -.
DR BioMuta; VDAC3; -.
DR DMDM; 12643945; -.
DR UCD-2DPAGE; Q9Y277; -.
DR CPTAC; CPTAC-448; -.
DR CPTAC; CPTAC-449; -.
DR EPD; Q9Y277; -.
DR jPOST; Q9Y277; -.
DR MassIVE; Q9Y277; -.
DR MaxQB; Q9Y277; -.
DR PaxDb; 9606-ENSP00000428845; -.
DR PeptideAtlas; Q9Y277; -.
DR ProteomicsDB; 85680; -. [Q9Y277-1]
DR ProteomicsDB; 85681; -. [Q9Y277-2]
DR Pumba; Q9Y277; -.
DR Antibodypedia; 11458; 248 antibodies from 29 providers.
DR DNASU; 7419; -.
DR Ensembl; ENST00000022615.9; ENSP00000022615.4; ENSG00000078668.14. [Q9Y277-1]
DR Ensembl; ENST00000521158.5; ENSP00000428845.1; ENSG00000078668.14. [Q9Y277-2]
DR GeneID; 7419; -.
DR KEGG; hsa:7419; -.
DR MANE-Select; ENST00000022615.9; ENSP00000022615.4; NM_005662.7; NP_005653.3.
DR UCSC; uc003xpc.4; human. [Q9Y277-1]
DR AGR; HGNC:12674; -.
DR CTD; 7419; -.
DR DisGeNET; 7419; -.
DR GeneCards; VDAC3; -.
DR HGNC; HGNC:12674; VDAC3.
DR HPA; ENSG00000078668; Group enriched (heart muscle, skeletal muscle, tongue).
DR MIM; 610029; gene.
DR neXtProt; NX_Q9Y277; -.
DR OpenTargets; ENSG00000078668; -.
DR PharmGKB; PA37297; -.
DR VEuPathDB; HostDB:ENSG00000078668; -.
DR eggNOG; KOG3126; Eukaryota.
DR GeneTree; ENSGT00950000182869; -.
DR HOGENOM; CLU_044399_2_0_1; -.
DR InParanoid; Q9Y277; -.
DR OMA; KGYHFGV; -.
DR OrthoDB; 2897965at2759; -.
DR PhylomeDB; Q9Y277; -.
DR TreeFam; TF315091; -.
DR PathwayCommons; Q9Y277; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8949215; Mitochondrial calcium ion transport.
DR SignaLink; Q9Y277; -.
DR BioGRID-ORCS; 7419; 37 hits in 1162 CRISPR screens.
DR ChiTaRS; VDAC3; human.
DR GeneWiki; VDAC3; -.
DR GenomeRNAi; 7419; -.
DR Pharos; Q9Y277; Tbio.
DR PRO; PR:Q9Y277; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9Y277; Protein.
DR Bgee; ENSG00000078668; Expressed in Brodmann (1909) area 23 and 215 other cell types or tissues.
DR ExpressionAtlas; Q9Y277; baseline and differential.
DR Genevisible; Q9Y277; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0046930; C:pore complex; IEA:UniProtKB-KW.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR GO; GO:0008308; F:voltage-gated monoatomic anion channel activity; IBA:GO_Central.
DR GO; GO:0015853; P:adenine transport; TAS:ProtInc.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0007270; P:neuron-neuron synaptic transmission; IEA:Ensembl.
DR GO; GO:0120317; P:sperm mitochondrial sheath assembly; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR CDD; cd07306; Porin3_VDAC; 1.
DR Gene3D; 2.40.160.10; Porin; 1.
DR InterPro; IPR023614; Porin_dom_sf.
DR InterPro; IPR001925; Porin_Euk.
DR InterPro; IPR027246; Porin_Euk/Tom40.
DR PANTHER; PTHR11743; VOLTAGE-DEPENDENT ANION-SELECTIVE CHANNEL; 1.
DR PANTHER; PTHR11743:SF28; VOLTAGE-DEPENDENT ANION-SELECTIVE CHANNEL PROTEIN 3; 1.
DR Pfam; PF01459; Porin_3; 1.
DR PRINTS; PR00185; EUKARYTPORIN.
DR PROSITE; PS00558; EUKARYOTIC_PORIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Ion transport; Isopeptide bond;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; NAD;
KW Nucleotide-binding; Phosphoprotein; Porin; Reference proteome;
KW Transmembrane; Transmembrane beta strand; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..283
FT /note="Voltage-dependent anion-selective channel protein 3"
FT /id="PRO_0000050512"
FT TRANSMEM 26..35
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 39..47
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 54..64
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 69..76
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 80..89
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 95..104
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 111..120
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 123..130
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 137..145
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 150..158
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 163..175
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 178..185
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 189..198
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 202..211
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 218..227
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 231..238
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 242..251
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 254..263
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 273..282
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT BINDING 242..244
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT BINDING 260..264
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT MOD_RES 2
FT /note="N-acetylcysteine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 4
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 12
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q60931"
FT MOD_RES 15
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q60931"
FT MOD_RES 20
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 90
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1Z0"
FT MOD_RES 266
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60931"
FT CROSSLNK 53
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 61
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 109
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 110
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 163
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 266
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 274
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT VAR_SEQ 39
FT /note="V -> VM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005079"
SQ SEQUENCE 283 AA; 30659 MW; E03CBCEDA72A9783 CRC64;
MCNTPTYCDL GKAAKDVFNK GYGFGMVKID LKTKSCSGVE FSTSGHAYTD TGKASGNLET
KYKVCNYGLT FTQKWNTDNT LGTEISWENK LAEGLKLTLD TIFVPNTGKK SGKLKASYKR
DCFSVGSNVD IDFSGPTIYG WAVLAFEGWL AGYQMSFDTA KSKLSQNNFA LGYKAADFQL
HTHVNDGTEF GGSIYQKVNE KIETSINLAW TAGSNNTRFG IAAKYMLDCR TSLSAKVNNA
SLIGLGYTQT LRPGVKLTLS ALIDGKNFSA GGHKVGLGFE LEA
//
