Full text data of VDAC2
VDAC2
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Voltage-dependent anion-selective channel protein 2; VDAC-2; hVDAC2 (Outer mitochondrial membrane protein porin 2)
Voltage-dependent anion-selective channel protein 2; VDAC-2; hVDAC2 (Outer mitochondrial membrane protein porin 2)
Comments
Isoform P45880-1 was detected.
Isoform P45880-1 was detected.
UniProt
P45880
ID VDAC2_HUMAN Reviewed; 294 AA.
AC P45880; Q5VWK1; Q5VWK3; Q6IB40; Q7L3J5; Q9BWK8; Q9Y5I6;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-SEP-2007, sequence version 2.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Voltage-dependent anion-selective channel protein 2;
DE Short=VDAC-2;
DE Short=hVDAC2;
DE AltName: Full=Outer mitochondrial membrane protein porin 2;
GN Name=VDAC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=B-cell;
RX PubMed=7685033;
RA Ha H., Hajek P., Bedwell D.M., Burrows P.D.;
RT "A mitochondrial porin cDNA predicts the existence of multiple human
RT porins.";
RL J. Biol. Chem. 268:12143-12149(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND VARIANT VAL-24.
RC TISSUE=Liver;
RX PubMed=8420959;
RA Blachly-Dyson E., Zambronicz E.B., Yu W.H., Adams V., McCabe E.R.,
RA Adelman J.P., Colombini M., Forte M.A.;
RT "Cloning and functional expression in yeast of two human isoforms of
RT the outer mitochondrial membrane channel, the voltage-dependent anion
RT channel.";
RL J. Biol. Chem. 268:1835-1841(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
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
RT loci by radiation hybrid analysis.";
RL Mamm. Genome 10:1041-1042(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Cervix, and Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 86-120; 178-229 AND 248-267, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 11-23 (ISOFORM 3), PROTEIN SEQUENCE OF 46-64;
RP 75-85; 108-120; 178-185; 236-263 AND 268-277 (ISOFORMS 1/2/3), AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=7539795; DOI=10.1074/jbc.270.23.13998;
RA Yu W.H., Wolfgang W., Forte M.A.;
RT "Subcellular localization of human voltage-dependent anion channel
RT isoforms.";
RL J. Biol. Chem. 270:13998-14006(1995).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-31, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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.,
RA Buerckstuemmer T., 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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane
CC that allows diffusion of small hydrophilic molecules. The channel
CC adopts an open conformation at low or zero membrane potential and
CC a closed conformation at potentials above 30-40 mV. The open state
CC has a weak anion selectivity whereas the closed state is cation-
CC selective.
CC -!- SUBUNIT: Interacts with hexokinases (By similarity).
CC -!- INTERACTION:
CC Q96A26:FAM162A; NbExp=2; IntAct=EBI-354022, EBI-6123466;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=P45880-3; Sequence=Displayed;
CC Name=1;
CC IsoId=P45880-1; Sequence=VSP_005077;
CC Note=Ref.1 (AAA60144) sequence differs from that shown due to a
CC frameshift in position 303;
CC Name=2;
CC IsoId=P45880-2; Sequence=VSP_005076;
CC Note=Ref.1 (AAA60145) sequence differs from that shown due to a
CC frameshift in position 277;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined.
CC -!- DOMAIN: Consists mainly of a membrane-spanning beta-barrel formed
CC by 19 beta-strands (By similarity).
CC -!- SIMILARITY: Belongs to the eukaryotic mitochondrial porin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH73106.1; Type=Erroneous gene model prediction;
CC Sequence=CAI40910.1; Type=Erroneous gene model prediction;
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DR EMBL; L08666; AAA60144.1; ALT_FRAME; mRNA.
DR EMBL; L08666; AAA60145.1; ALT_FRAME; mRNA.
DR EMBL; L06328; AAB59457.1; -; mRNA.
DR EMBL; AF152227; AAD40241.1; -; Genomic_DNA.
DR EMBL; AF152220; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152221; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152222; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152223; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152224; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152225; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152226; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; CR456964; CAG33245.1; -; mRNA.
DR EMBL; AL390034; CAH73108.1; -; Genomic_DNA.
DR EMBL; AL392111; CAH73108.1; JOINED; Genomic_DNA.
DR EMBL; AL392111; CAI40914.1; -; Genomic_DNA.
DR EMBL; AL390034; CAI40914.1; JOINED; Genomic_DNA.
DR EMBL; AL390034; CAH73107.1; -; Genomic_DNA.
DR EMBL; AL392111; CAH73107.1; JOINED; Genomic_DNA.
DR EMBL; AL392111; CAI40911.1; -; Genomic_DNA.
DR EMBL; AL390034; CAI40911.1; JOINED; Genomic_DNA.
DR EMBL; AL390034; CAH73106.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL392111; CAH73106.1; JOINED; Genomic_DNA.
DR EMBL; AL392111; CAI40910.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL390034; CAI40910.1; JOINED; Genomic_DNA.
DR EMBL; BC000165; AAH00165.2; -; mRNA.
DR EMBL; BC012883; AAH12883.2; -; mRNA.
DR EMBL; BC072407; AAH72407.1; -; mRNA.
DR PIR; A45972; A45972.
DR PIR; B44422; B44422.
DR RefSeq; NP_001171712.1; NM_001184783.1.
DR RefSeq; NP_001171752.1; NM_001184823.1.
DR RefSeq; NP_003366.2; NM_003375.3.
DR UniGene; Hs.355927; -.
DR ProteinModelPortal; P45880; -.
DR SMR; P45880; 12-294.
DR IntAct; P45880; 16.
DR MINT; MINT-3016132; -.
DR STRING; 9606.ENSP00000361686; -.
DR ChEMBL; CHEMBL6190; -.
DR DrugBank; DB01375; Dihydroxyaluminium.
DR PhosphoSite; P45880; -.
DR DMDM; 158518391; -.
DR DOSAC-COBS-2DPAGE; P45880; -.
DR OGP; P45880; -.
DR REPRODUCTION-2DPAGE; P45880; -.
DR SWISS-2DPAGE; P45880; -.
DR UCD-2DPAGE; P45880; -.
DR PaxDb; P45880; -.
DR PRIDE; P45880; -.
DR DNASU; 7417; -.
DR Ensembl; ENST00000313132; ENSP00000361635; ENSG00000165637.
DR Ensembl; ENST00000332211; ENSP00000361686; ENSG00000165637.
DR Ensembl; ENST00000543351; ENSP00000443092; ENSG00000165637.
DR GeneID; 7417; -.
DR KEGG; hsa:7417; -.
DR UCSC; uc001jwz.3; human.
DR CTD; 7417; -.
DR GeneCards; GC10P076969; -.
DR H-InvDB; HIX0029994; -.
DR HGNC; HGNC:12672; VDAC2.
DR HPA; HPA043475; -.
DR MIM; 193245; gene.
DR neXtProt; NX_P45880; -.
DR PharmGKB; PA37295; -.
DR eggNOG; NOG243169; -.
DR HOVERGEN; HBG054036; -.
DR KO; K15040; -.
DR OMA; MCVPPSY; -.
DR OrthoDB; EOG7P8P8G; -.
DR GeneWiki; VDAC2; -.
DR GenomeRNAi; 7417; -.
DR NextBio; 29042; -.
DR PRO; PR:P45880; -.
DR ArrayExpress; P45880; -.
DR Bgee; P45880; -.
DR CleanEx; HS_VDAC2; -.
DR Genevestigator; P45880; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:ProtInc.
DR GO; GO:0046930; C:pore complex; IEA:UniProtKB-KW.
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 anion channel activity; TAS:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0032272; P:negative regulation of protein polymerization; IEA:Ensembl.
DR Gene3D; 2.40.160.10; -; 1.
DR InterPro; IPR023614; Porin_dom.
DR InterPro; IPR001925; Porin_Euk.
DR InterPro; IPR027246; Porin_Euk/Tom40.
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; Complete proteome;
KW Direct protein sequencing; Ion transport; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; NAD; Nucleotide-binding; Polymorphism;
KW Porin; Reference proteome; Transmembrane; Transmembrane beta strand;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 294 Voltage-dependent anion-selective channel
FT protein 2.
FT /FTId=PRO_0000050505.
FT TRANSMEM 37 46 Beta stranded; (By similarity).
FT TRANSMEM 50 58 Beta stranded; (By similarity).
FT TRANSMEM 65 75 Beta stranded; (By similarity).
FT TRANSMEM 80 87 Beta stranded; (By similarity).
FT TRANSMEM 91 100 Beta stranded; (By similarity).
FT TRANSMEM 106 115 Beta stranded; (By similarity).
FT TRANSMEM 122 131 Beta stranded; (By similarity).
FT TRANSMEM 134 141 Beta stranded; (By similarity).
FT TRANSMEM 148 156 Beta stranded; (By similarity).
FT TRANSMEM 161 169 Beta stranded; (By similarity).
FT TRANSMEM 174 186 Beta stranded; (By similarity).
FT TRANSMEM 189 196 Beta stranded; (By similarity).
FT TRANSMEM 200 209 Beta stranded; (By similarity).
FT TRANSMEM 213 222 Beta stranded; (By similarity).
FT TRANSMEM 229 238 Beta stranded; (By similarity).
FT TRANSMEM 242 249 Beta stranded; (By similarity).
FT TRANSMEM 253 262 Beta stranded; (By similarity).
FT TRANSMEM 265 274 Beta stranded; (By similarity).
FT TRANSMEM 284 293 Beta stranded; (By similarity).
FT NP_BIND 253 255 NAD (By similarity).
FT NP_BIND 271 275 NAD (By similarity).
FT SITE 84 84 Involved in hexokinase binding (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 31 31 N6-acetyllysine.
FT MOD_RES 120 120 N6-acetyllysine (By similarity).
FT VAR_SEQ 1 11 MATHGQTCARP -> MSWCNELRLPALKQHSIGRGLESHIT
FT (in isoform 1).
FT /FTId=VSP_005077.
FT VAR_SEQ 1 11 Missing (in isoform 2).
FT /FTId=VSP_005076.
FT VARIANT 24 24 A -> V.
FT /FTId=VAR_006380.
SQ SEQUENCE 294 AA; 31567 MW; F4EAE732E653637E CRC64;
MATHGQTCAR PMCIPPSYAD LGKAARDIFN KGFGFGLVKL DVKTKSCSGV EFSTSGSSNT
DTGKVTGTLE TKYKWCEYGL TFTEKWNTDN TLGTEIAIED QICQGLKLTF DTTFSPNTGK
KSGKIKSSYK RECINLGCDV DFDFAGPAIH GSAVFGYEGW LAGYQMTFDS AKSKLTRNNF
AVGYRTGDFQ LHTNVNDGTE FGGSIYQKVC EDLDTSVNLA WTSGTNCTRF GIAAKYQLDP
TASISAKVNN SSLIGVGYTQ TLRPGVKLTL SALVDGKSIN AGGHKVGLAL ELEA
//
ID VDAC2_HUMAN Reviewed; 294 AA.
AC P45880; Q5VWK1; Q5VWK3; Q6IB40; Q7L3J5; Q9BWK8; Q9Y5I6;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-SEP-2007, sequence version 2.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Voltage-dependent anion-selective channel protein 2;
DE Short=VDAC-2;
DE Short=hVDAC2;
DE AltName: Full=Outer mitochondrial membrane protein porin 2;
GN Name=VDAC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=B-cell;
RX PubMed=7685033;
RA Ha H., Hajek P., Bedwell D.M., Burrows P.D.;
RT "A mitochondrial porin cDNA predicts the existence of multiple human
RT porins.";
RL J. Biol. Chem. 268:12143-12149(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND VARIANT VAL-24.
RC TISSUE=Liver;
RX PubMed=8420959;
RA Blachly-Dyson E., Zambronicz E.B., Yu W.H., Adams V., McCabe E.R.,
RA Adelman J.P., Colombini M., Forte M.A.;
RT "Cloning and functional expression in yeast of two human isoforms of
RT the outer mitochondrial membrane channel, the voltage-dependent anion
RT channel.";
RL J. Biol. Chem. 268:1835-1841(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
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
RT loci by radiation hybrid analysis.";
RL Mamm. Genome 10:1041-1042(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Cervix, and Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 86-120; 178-229 AND 248-267, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 11-23 (ISOFORM 3), PROTEIN SEQUENCE OF 46-64;
RP 75-85; 108-120; 178-185; 236-263 AND 268-277 (ISOFORMS 1/2/3), AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=7539795; DOI=10.1074/jbc.270.23.13998;
RA Yu W.H., Wolfgang W., Forte M.A.;
RT "Subcellular localization of human voltage-dependent anion channel
RT isoforms.";
RL J. Biol. Chem. 270:13998-14006(1995).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-31, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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.,
RA Buerckstuemmer T., 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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane
CC that allows diffusion of small hydrophilic molecules. The channel
CC adopts an open conformation at low or zero membrane potential and
CC a closed conformation at potentials above 30-40 mV. The open state
CC has a weak anion selectivity whereas the closed state is cation-
CC selective.
CC -!- SUBUNIT: Interacts with hexokinases (By similarity).
CC -!- INTERACTION:
CC Q96A26:FAM162A; NbExp=2; IntAct=EBI-354022, EBI-6123466;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=P45880-3; Sequence=Displayed;
CC Name=1;
CC IsoId=P45880-1; Sequence=VSP_005077;
CC Note=Ref.1 (AAA60144) sequence differs from that shown due to a
CC frameshift in position 303;
CC Name=2;
CC IsoId=P45880-2; Sequence=VSP_005076;
CC Note=Ref.1 (AAA60145) sequence differs from that shown due to a
CC frameshift in position 277;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined.
CC -!- DOMAIN: Consists mainly of a membrane-spanning beta-barrel formed
CC by 19 beta-strands (By similarity).
CC -!- SIMILARITY: Belongs to the eukaryotic mitochondrial porin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH73106.1; Type=Erroneous gene model prediction;
CC Sequence=CAI40910.1; Type=Erroneous gene model prediction;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
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DR EMBL; L08666; AAA60144.1; ALT_FRAME; mRNA.
DR EMBL; L08666; AAA60145.1; ALT_FRAME; mRNA.
DR EMBL; L06328; AAB59457.1; -; mRNA.
DR EMBL; AF152227; AAD40241.1; -; Genomic_DNA.
DR EMBL; AF152220; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152221; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152222; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152223; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152224; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152225; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; AF152226; AAD40241.1; JOINED; Genomic_DNA.
DR EMBL; CR456964; CAG33245.1; -; mRNA.
DR EMBL; AL390034; CAH73108.1; -; Genomic_DNA.
DR EMBL; AL392111; CAH73108.1; JOINED; Genomic_DNA.
DR EMBL; AL392111; CAI40914.1; -; Genomic_DNA.
DR EMBL; AL390034; CAI40914.1; JOINED; Genomic_DNA.
DR EMBL; AL390034; CAH73107.1; -; Genomic_DNA.
DR EMBL; AL392111; CAH73107.1; JOINED; Genomic_DNA.
DR EMBL; AL392111; CAI40911.1; -; Genomic_DNA.
DR EMBL; AL390034; CAI40911.1; JOINED; Genomic_DNA.
DR EMBL; AL390034; CAH73106.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL392111; CAH73106.1; JOINED; Genomic_DNA.
DR EMBL; AL392111; CAI40910.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL390034; CAI40910.1; JOINED; Genomic_DNA.
DR EMBL; BC000165; AAH00165.2; -; mRNA.
DR EMBL; BC012883; AAH12883.2; -; mRNA.
DR EMBL; BC072407; AAH72407.1; -; mRNA.
DR PIR; A45972; A45972.
DR PIR; B44422; B44422.
DR RefSeq; NP_001171712.1; NM_001184783.1.
DR RefSeq; NP_001171752.1; NM_001184823.1.
DR RefSeq; NP_003366.2; NM_003375.3.
DR UniGene; Hs.355927; -.
DR ProteinModelPortal; P45880; -.
DR SMR; P45880; 12-294.
DR IntAct; P45880; 16.
DR MINT; MINT-3016132; -.
DR STRING; 9606.ENSP00000361686; -.
DR ChEMBL; CHEMBL6190; -.
DR DrugBank; DB01375; Dihydroxyaluminium.
DR PhosphoSite; P45880; -.
DR DMDM; 158518391; -.
DR DOSAC-COBS-2DPAGE; P45880; -.
DR OGP; P45880; -.
DR REPRODUCTION-2DPAGE; P45880; -.
DR SWISS-2DPAGE; P45880; -.
DR UCD-2DPAGE; P45880; -.
DR PaxDb; P45880; -.
DR PRIDE; P45880; -.
DR DNASU; 7417; -.
DR Ensembl; ENST00000313132; ENSP00000361635; ENSG00000165637.
DR Ensembl; ENST00000332211; ENSP00000361686; ENSG00000165637.
DR Ensembl; ENST00000543351; ENSP00000443092; ENSG00000165637.
DR GeneID; 7417; -.
DR KEGG; hsa:7417; -.
DR UCSC; uc001jwz.3; human.
DR CTD; 7417; -.
DR GeneCards; GC10P076969; -.
DR H-InvDB; HIX0029994; -.
DR HGNC; HGNC:12672; VDAC2.
DR HPA; HPA043475; -.
DR MIM; 193245; gene.
DR neXtProt; NX_P45880; -.
DR PharmGKB; PA37295; -.
DR eggNOG; NOG243169; -.
DR HOVERGEN; HBG054036; -.
DR KO; K15040; -.
DR OMA; MCVPPSY; -.
DR OrthoDB; EOG7P8P8G; -.
DR GeneWiki; VDAC2; -.
DR GenomeRNAi; 7417; -.
DR NextBio; 29042; -.
DR PRO; PR:P45880; -.
DR ArrayExpress; P45880; -.
DR Bgee; P45880; -.
DR CleanEx; HS_VDAC2; -.
DR Genevestigator; P45880; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:ProtInc.
DR GO; GO:0046930; C:pore complex; IEA:UniProtKB-KW.
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 anion channel activity; TAS:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0032272; P:negative regulation of protein polymerization; IEA:Ensembl.
DR Gene3D; 2.40.160.10; -; 1.
DR InterPro; IPR023614; Porin_dom.
DR InterPro; IPR001925; Porin_Euk.
DR InterPro; IPR027246; Porin_Euk/Tom40.
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; Complete proteome;
KW Direct protein sequencing; Ion transport; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; NAD; Nucleotide-binding; Polymorphism;
KW Porin; Reference proteome; Transmembrane; Transmembrane beta strand;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 294 Voltage-dependent anion-selective channel
FT protein 2.
FT /FTId=PRO_0000050505.
FT TRANSMEM 37 46 Beta stranded; (By similarity).
FT TRANSMEM 50 58 Beta stranded; (By similarity).
FT TRANSMEM 65 75 Beta stranded; (By similarity).
FT TRANSMEM 80 87 Beta stranded; (By similarity).
FT TRANSMEM 91 100 Beta stranded; (By similarity).
FT TRANSMEM 106 115 Beta stranded; (By similarity).
FT TRANSMEM 122 131 Beta stranded; (By similarity).
FT TRANSMEM 134 141 Beta stranded; (By similarity).
FT TRANSMEM 148 156 Beta stranded; (By similarity).
FT TRANSMEM 161 169 Beta stranded; (By similarity).
FT TRANSMEM 174 186 Beta stranded; (By similarity).
FT TRANSMEM 189 196 Beta stranded; (By similarity).
FT TRANSMEM 200 209 Beta stranded; (By similarity).
FT TRANSMEM 213 222 Beta stranded; (By similarity).
FT TRANSMEM 229 238 Beta stranded; (By similarity).
FT TRANSMEM 242 249 Beta stranded; (By similarity).
FT TRANSMEM 253 262 Beta stranded; (By similarity).
FT TRANSMEM 265 274 Beta stranded; (By similarity).
FT TRANSMEM 284 293 Beta stranded; (By similarity).
FT NP_BIND 253 255 NAD (By similarity).
FT NP_BIND 271 275 NAD (By similarity).
FT SITE 84 84 Involved in hexokinase binding (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 31 31 N6-acetyllysine.
FT MOD_RES 120 120 N6-acetyllysine (By similarity).
FT VAR_SEQ 1 11 MATHGQTCARP -> MSWCNELRLPALKQHSIGRGLESHIT
FT (in isoform 1).
FT /FTId=VSP_005077.
FT VAR_SEQ 1 11 Missing (in isoform 2).
FT /FTId=VSP_005076.
FT VARIANT 24 24 A -> V.
FT /FTId=VAR_006380.
SQ SEQUENCE 294 AA; 31567 MW; F4EAE732E653637E CRC64;
MATHGQTCAR PMCIPPSYAD LGKAARDIFN KGFGFGLVKL DVKTKSCSGV EFSTSGSSNT
DTGKVTGTLE TKYKWCEYGL TFTEKWNTDN TLGTEIAIED QICQGLKLTF DTTFSPNTGK
KSGKIKSSYK RECINLGCDV DFDFAGPAIH GSAVFGYEGW LAGYQMTFDS AKSKLTRNNF
AVGYRTGDFQ LHTNVNDGTE FGGSIYQKVC EDLDTSVNLA WTSGTNCTRF GIAAKYQLDP
TASISAKVNN SSLIGVGYTQ TLRPGVKLTL SALVDGKSIN AGGHKVGLAL ELEA
//
MIM
193245
*RECORD*
*FIELD* NO
193245
*FIELD* TI
*193245 VOLTAGE-DEPENDENT ANION CHANNEL 2; VDAC2
*FIELD* TX
CLONING
The voltage-dependent anion channel (VDAC) of the outer mitochondrial
read moremembrane, a small abundant protein found in all eukaryotic kingdoms,
forms a voltage-gated pore when incorporated into planar lipid bilayers.
VDAC is also the site of binding of the metabolic enzymes hexokinase and
glycerol kinase to the mitochondrion in what may be a significant
metabolic regulatory interaction. Blachly-Dyson et al. (1993) identified
and characterized 2 human cDNAs encoding VDAC homologs. To confirm VDAC
function, each human protein was expressed in yeast lacking the
endogenous VDAC gene. Human proteins isolated from yeast mitochondria
formed channels with the characteristics expected of VDAC when
incorporated into planar lipid bilayers. In addition, expression of the
human proteins in such strains complemented phenotypic defects
associated with elimination of the endogenous yeast VDAC gene.
Mitochondria expressing VDAC1 (604492) were capable of specifically
binding hexokinase, whereas mitochondria expressing VDAC2 only bound
hexokinase at background levels. Each human cDNA was expressed in
essentially all human cell lines and tissues examined. Huizing et al.
(1998) studied the human tissue distribution of mitochondrial
transmembrane metabolite carriers by Northern and Western blot analyses.
VDAC2 appeared to be expressed only in the heart.
GENE FUNCTION
Cheng et al. (2003) found that in viable cells, BAK (600516) complexed
with the mitochondrial outer membrane protein VDAC2, a VDAC isoform
present in low abundance that interacts specifically with the inactive
conformer of BAK. Cells deficient in VDAC2, but not cells lacking the
more abundant VDAC1 exhibited enhanced BAK oligomerization and were more
susceptible to apoptotic death. Conversely, overexpression of VDAC2
selectively prevented BAK activation and inhibited the mitochondrial
apoptotic pathway. Death signals activate 'BH3-only' molecules such as
tBID (601997), BIM (603827), or BAD (603167), which displace VDAC2 from
BAK, enabling homooligomerization of BAK and apoptosis. Thus, Cheng et
al. (2003) concluded that VDAC2, an isoform restricted to mammals,
regulates the activity of BAK and provides a connection between
mitochondrial physiology and the core apoptotic pathway.
Yogoda et al. (2007) described the mechanism of action of the selective
antitumor agent erastin, involving the RAS-RAF-MEK signaling pathway
functioning in cell proliferation, differentiation, and survival.
Erastin exhibits greater lethality in human tumor cells harboring
mutations in the oncogenes HRAS (190020), KRAS (190070), or BRAF
(164757). Using affinity purification and mass spectrometry, Yogoda et
al. (2007) discovered that erastin acts through mitochondrial
voltage-dependent anion channels (VDACs), a novel target for anticancer
drugs. Yogoda et al. (2007) showed that erastin treatment of cells
harboring oncogenic RAS causes the appearance of oxidative species and
subsequent death through an oxidative, nonapoptotic mechanism. RNA
interference-mediated knockdown of VDAC2 or VDAC3 (610029) caused
resistance to erastin, implicating these 2 VDAC isoforms in the
mechanism of action of erastin. Moreover, using purified mitochondria
expressing a single VDAC isoform, Yogoda et al. (2007) found that
erastin alters the permeability of the outer mitochondrial membrane.
Finally, using a radiolabeled analog and a filter-binding assay, Yogoda
et al. (2007) showed that erastin binds directly to VDAC2. Yogoda et al.
(2007) concluded that ligands to VDAC proteins can induce nonapoptotic
cell death selectively in some tumor cells harboring activating
mutations in the RAS-RAF-MEK pathway.
MAPPING
By application of the polymerase chain reaction and restriction analysis
to the study of a human/rodent somatic cell mapping panel, Blachly-Dyson
et al. (1994) had mapped the VDAC2 gene to chromosome 21. Messina et al.
(1999) used fluorescence in situ hybridization analysis to map the VDAC2
gene to chromosome 10q22. The homologous murine gene Vdac2 maps on the
proximal region of mouse chromosome 14, a region of synteny between
mouse and human, supporting the results of Messina et al. (1999) that
the correct location of VDAC2 is 10q22.
*FIELD* RF
1. Blachly-Dyson, E.; Baldini, A.; Litt, M.; McCabe, E. R. B.; Forte,
M.: Human genes encoding the voltage-dependent anion channel (VDAC)
of the outer mitochondrial membrane: mapping and identification of
two new isoforms. Genomics 20: 62-67, 1994.
2. Blachly-Dyson, E.; Zambronicz, E. B.; Yu, W. H.; Adams, V.; McCabe,
E. R. B.; Adelman, J.; Colombini, M.; Forte, M.: Cloning and functional
expression in yeast of two human isoforms of the outer mitochondrial
membrane channel, the voltage-dependent anion channel. J. Biol. Chem. 268:
1835-1841, 1993.
3. Cheng, E. H.-Y.; Sheiko, T. V.; Fisher, J. K.; Craigen, W. J.;
Korsmeyer, S. J.: VDAC2 inhibits BAK activation and mitochondrial
apoptosis. Science 301: 513-517, 2003.
4. Huizing, M.; Ruitenbeek, W.; van den Heuvel, L. P.; Dolce, V.;
Iacobazzi, V.; Smeitink, J. A. M.; Palmieri, F.; Trijbels, J. M. F.
: Human mitochondrial transmembrane metabolite carriers: tissue distribution
and its implication for mitochondrial disorders. J. Bioenerg. Biomembr. 30:
277-284, 1998.
5. Messina, A.; Oliva, M.; Rosato, C.; Huizing, M.; Ruitenbeek, W.;
van den Heuvel, L. P.; Forte, M.; Rocchi, M.; De Pinto, V.: Mapping
of the human voltage-dependent action channel isoforms 1 and 2 reconsidered. Biochem.
Biophys. Res. Commun. 255: 707-710, 1999.
6. Yogoda, N.; von Rechenberg, M.; Zaganjor, E.; Bauer, A. J.; Yang,
W. S.; Fridman, D. J.; Wolpaw, A. J.; Smukste, I.; Peltier, J. M.;
Boniface, J. J.; Smith, R.; Lessnick, S. L.; Sahasrabudhe, S.; Stockwell,
B. R.: RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent
anion channels. Nature 447: 864-868, 2007.
*FIELD* CN
Ada Hamosh - updated: 6/29/2007
Ada Hamosh - updated: 7/30/2003
Ada Hamosh - updated: 2/1/2000
Wilson H. Y. Lo - updated: 8/10/1999
*FIELD* CD
Victor A. McKusick: 4/8/1994
*FIELD* ED
alopez: 07/03/2007
alopez: 7/3/2007
terry: 6/29/2007
alopez: 8/4/2003
terry: 7/30/2003
alopez: 2/2/2000
terry: 2/1/2000
carol: 8/10/1999
dkim: 7/17/1998
jason: 6/7/1994
carol: 4/8/1994
*RECORD*
*FIELD* NO
193245
*FIELD* TI
*193245 VOLTAGE-DEPENDENT ANION CHANNEL 2; VDAC2
*FIELD* TX
CLONING
The voltage-dependent anion channel (VDAC) of the outer mitochondrial
read moremembrane, a small abundant protein found in all eukaryotic kingdoms,
forms a voltage-gated pore when incorporated into planar lipid bilayers.
VDAC is also the site of binding of the metabolic enzymes hexokinase and
glycerol kinase to the mitochondrion in what may be a significant
metabolic regulatory interaction. Blachly-Dyson et al. (1993) identified
and characterized 2 human cDNAs encoding VDAC homologs. To confirm VDAC
function, each human protein was expressed in yeast lacking the
endogenous VDAC gene. Human proteins isolated from yeast mitochondria
formed channels with the characteristics expected of VDAC when
incorporated into planar lipid bilayers. In addition, expression of the
human proteins in such strains complemented phenotypic defects
associated with elimination of the endogenous yeast VDAC gene.
Mitochondria expressing VDAC1 (604492) were capable of specifically
binding hexokinase, whereas mitochondria expressing VDAC2 only bound
hexokinase at background levels. Each human cDNA was expressed in
essentially all human cell lines and tissues examined. Huizing et al.
(1998) studied the human tissue distribution of mitochondrial
transmembrane metabolite carriers by Northern and Western blot analyses.
VDAC2 appeared to be expressed only in the heart.
GENE FUNCTION
Cheng et al. (2003) found that in viable cells, BAK (600516) complexed
with the mitochondrial outer membrane protein VDAC2, a VDAC isoform
present in low abundance that interacts specifically with the inactive
conformer of BAK. Cells deficient in VDAC2, but not cells lacking the
more abundant VDAC1 exhibited enhanced BAK oligomerization and were more
susceptible to apoptotic death. Conversely, overexpression of VDAC2
selectively prevented BAK activation and inhibited the mitochondrial
apoptotic pathway. Death signals activate 'BH3-only' molecules such as
tBID (601997), BIM (603827), or BAD (603167), which displace VDAC2 from
BAK, enabling homooligomerization of BAK and apoptosis. Thus, Cheng et
al. (2003) concluded that VDAC2, an isoform restricted to mammals,
regulates the activity of BAK and provides a connection between
mitochondrial physiology and the core apoptotic pathway.
Yogoda et al. (2007) described the mechanism of action of the selective
antitumor agent erastin, involving the RAS-RAF-MEK signaling pathway
functioning in cell proliferation, differentiation, and survival.
Erastin exhibits greater lethality in human tumor cells harboring
mutations in the oncogenes HRAS (190020), KRAS (190070), or BRAF
(164757). Using affinity purification and mass spectrometry, Yogoda et
al. (2007) discovered that erastin acts through mitochondrial
voltage-dependent anion channels (VDACs), a novel target for anticancer
drugs. Yogoda et al. (2007) showed that erastin treatment of cells
harboring oncogenic RAS causes the appearance of oxidative species and
subsequent death through an oxidative, nonapoptotic mechanism. RNA
interference-mediated knockdown of VDAC2 or VDAC3 (610029) caused
resistance to erastin, implicating these 2 VDAC isoforms in the
mechanism of action of erastin. Moreover, using purified mitochondria
expressing a single VDAC isoform, Yogoda et al. (2007) found that
erastin alters the permeability of the outer mitochondrial membrane.
Finally, using a radiolabeled analog and a filter-binding assay, Yogoda
et al. (2007) showed that erastin binds directly to VDAC2. Yogoda et al.
(2007) concluded that ligands to VDAC proteins can induce nonapoptotic
cell death selectively in some tumor cells harboring activating
mutations in the RAS-RAF-MEK pathway.
MAPPING
By application of the polymerase chain reaction and restriction analysis
to the study of a human/rodent somatic cell mapping panel, Blachly-Dyson
et al. (1994) had mapped the VDAC2 gene to chromosome 21. Messina et al.
(1999) used fluorescence in situ hybridization analysis to map the VDAC2
gene to chromosome 10q22. The homologous murine gene Vdac2 maps on the
proximal region of mouse chromosome 14, a region of synteny between
mouse and human, supporting the results of Messina et al. (1999) that
the correct location of VDAC2 is 10q22.
*FIELD* RF
1. Blachly-Dyson, E.; Baldini, A.; Litt, M.; McCabe, E. R. B.; Forte,
M.: Human genes encoding the voltage-dependent anion channel (VDAC)
of the outer mitochondrial membrane: mapping and identification of
two new isoforms. Genomics 20: 62-67, 1994.
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*FIELD* CN
Ada Hamosh - updated: 6/29/2007
Ada Hamosh - updated: 7/30/2003
Ada Hamosh - updated: 2/1/2000
Wilson H. Y. Lo - updated: 8/10/1999
*FIELD* CD
Victor A. McKusick: 4/8/1994
*FIELD* ED
alopez: 07/03/2007
alopez: 7/3/2007
terry: 6/29/2007
alopez: 8/4/2003
terry: 7/30/2003
alopez: 2/2/2000
terry: 2/1/2000
carol: 8/10/1999
dkim: 7/17/1998
jason: 6/7/1994
carol: 4/8/1994