Full text data of VDAC1
VDAC1
(VDAC)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Voltage-dependent anion-selective channel protein 1; VDAC-1; hVDAC1 (Outer mitochondrial membrane protein porin 1; Plasmalemmal porin; Porin 31HL; Porin 31HM)
Voltage-dependent anion-selective channel protein 1; VDAC-1; hVDAC1 (Outer mitochondrial membrane protein porin 1; Plasmalemmal porin; Porin 31HL; Porin 31HM)
UniProt
P21796
ID VDAC1_HUMAN Reviewed; 283 AA.
AC P21796; B3KVK4; D3DQ93; Q5FVE7; Q9UIQ5; Q9UPL0;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Voltage-dependent anion-selective channel protein 1;
DE Short=VDAC-1;
DE Short=hVDAC1;
DE AltName: Full=Outer mitochondrial membrane protein porin 1;
DE AltName: Full=Plasmalemmal porin;
DE AltName: Full=Porin 31HL;
DE AltName: Full=Porin 31HM;
GN Name=VDAC1; Synonyms=VDAC;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pituitary;
RA Blachly-Dyson E., Forte M.A.;
RT "Cloning of human VDAC cDNA.";
RL Biophys. J. 59:216A-216A(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [GENOMIC DNA].
RX PubMed=10772903; DOI=10.1006/bbrc.2000.2487;
RA Messina A., Guarino F., Oliva M., van den Heuvel L.P., Smeitink J.,
RA De Pinto V.;
RT "Characterization of the human porin isoform 1 (HVDAC1) gene by
RT amplification on the whole human genome: a tool for porin deficiency
RT analysis.";
RL Biochem. Biophys. Res. Commun. 270:787-792(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 2-283.
RC TISSUE=Lymphocyte;
RX PubMed=2559745;
RA Kayser H., Kratzin H.D., Thinnes F.P., Goetz H., Schmidt W.E.,
RA Eckart K., Hilschmann N.;
RT "Identification of human porins. II. Characterization and primary
RT structure of a 31-lDa porin from human B lymphocytes (Porin 31HL).";
RL Biol. Chem. Hoppe-Seyler 370:1265-1278(1989).
RN [10]
RP PROTEIN SEQUENCE OF 2-283.
RC TISSUE=Skeletal muscle;
RX PubMed=1657034;
RA Juergens L., Ilsemann P., Kratzin H.D., Hesse D., Eckart K.,
RA Thinnes F.P., Hilschmann N.;
RT "Studies on human porin. IV. The primary structures of 'Porin 31HM'
RT purified from human skeletal muscle membranes and of 'Porin 31HL'
RT derived from human B lymphocyte membranes are identical.";
RL Biol. Chem. Hoppe-Seyler 372:455-463(1991).
RN [11]
RP PROTEIN SEQUENCE OF 2-283.
RC TISSUE=B-cell;
RA Hein A., Kiafard Z., Hesse D., Hesse J.-O., Zimmermann B.,
RA Kratzin H.D., Schulz H., Reiss J., Thinnes F.P., Goetz H.,
RA Hilschmann N.;
RL Submitted (DEC-1997) to UniProtKB.
RN [12]
RP PROTEIN SEQUENCE OF 2-12; 21-61; 64-74; 94-110; 121-139; 162-174;
RP 225-236 AND 257-274, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 75-93; 175-197 AND 201-218, AND MASS 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 [14]
RP MUTAGENESIS.
RX PubMed=7685903; DOI=10.1073/pnas.90.12.5446;
RA Thomas L., Blachly-Dyson E., Colombini M., Forte M.A.;
RT "Mapping of residues forming the voltage sensor of the voltage-
RT dependent anion-selective channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5446-5449(1993).
RN [15]
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 [16]
RP CHARACTERIZATION, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=10661876; DOI=10.1515/BC.1999.189;
RA Stadtmueller U., Eben-Brunnen J., Schmid A., Hesse D., Klebert S.,
RA Kratzin H.D., Hesse J., Zimmermann B., Reymann S., Thinnes F.P.,
RA Benz R., Goetz H., Hilschmann N.;
RT "Mitochondria-derived and extra-mitochondrial human type-1 porin are
RT identical as revealed by amino acid sequencing and
RT electrophysiological characterisation.";
RL Biol. Chem. 380:1461-1466(1999).
RN [17]
RP FUNCTION.
RX PubMed=11845315; DOI=10.1007/s004240100656;
RA Thinnes F.P., Walter G., Hellmann K.P., Hellmann T., Merker R.,
RA Kiafard Z., Eben-Brunnen J., Schwarzer C., Goetz H., Hilschmann N.;
RT "Gadolinium as an opener of the outwardly rectifying Cl(-) channel
RT (ORCC). Is there relevance for cystic fibrosis therapy?";
RL Pflugers Arch. 443:S111-S116(2001).
RN [18]
RP FUNCTION IN APOPTOSIS.
RX PubMed=15033708; DOI=10.1196/annals.1299.022;
RA Verrier F., Mignotte B., Jan G., Brenner C.;
RT "Study of PTPC composition during apoptosis for identification of
RT viral protein target.";
RL Ann. N. Y. Acad. Sci. 1010:126-142(2003).
RN [19]
RP INTERACTION WITH INFLUENZA A VIRUS PB1-F2.
RX PubMed=16201016; DOI=10.1371/journal.ppat.0010004;
RA Zamarin D., Garcia-Sastre A., Xiao X., Wang R., Palese P.;
RT "Influenza virus PB1-F2 protein induces cell death through
RT mitochondrial ANT3 and VDAC1.";
RL PLoS Pathog. 1:40-54(2005).
RN [20]
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 [21]
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 [22]
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 [23]
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 [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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 [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-20 AND LYS-266, AND MASS
RP 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 [26]
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 [27]
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 [28]
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).
RN [29]
RP INTERACTION WITH ATF2 AND HK1.
RX PubMed=22304920; DOI=10.1016/j.cell.2012.01.016;
RA Lau E., Kluger H., Varsano T., Lee K., Scheffler I., Rimm D.L.,
RA Ideker T., Ronai Z.A.;
RT "PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while
RT blocking its apoptotic function at mitochondria.";
RL Cell 148:543-555(2012).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP INTERACTION WITH BOP/C22ORF29.
RX PubMed=23055042; DOI=10.1007/s13238-012-2069-7;
RA Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q.,
RA Pan L., Tang H.;
RT "Human Bop is a novel BH3-only member of the Bcl-2 protein family.";
RL Protein Cell 3:790-801(2012).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (4.1 ANGSTROMS) OF 2-283, AND STRUCTURE BY NMR.
RX PubMed=18832158; DOI=10.1073/pnas.0808115105;
RA Bayrhuber M., Meins T., Habeck M., Becker S., Giller K., Villinger S.,
RA Vonrhein C., Griesinger C., Zweckstetter M., Zeth K.;
RT "Structure of the human voltage-dependent anion channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:15370-15375(2008).
RN [33]
RP STRUCTURE BY NMR, FUNCTION, INTERACTION WITH BCL2L1, AND NADH-BINDING.
RX PubMed=18755977; DOI=10.1126/science.1161302;
RA Hiller S., Garces R.G., Malia T.J., Orekhov V.Y., Colombini M.,
RA Wagner G.;
RT "Solution structure of the integral human membrane protein VDAC-1 in
RT detergent micelles.";
RL Science 321:1206-1210(2008).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane
CC and also the plasma membrane. The channel at the outer
CC mitochondrial membrane allows diffusion of small hydrophilic
CC molecules; in the plasma membrane it is involved in cell volume
CC regulation and apoptosis. It adopts an open conformation at low or
CC zero membrane potential and a closed conformation at potentials
CC above 30-40 mV. The open state has a weak anion selectivity
CC whereas the closed state is cation-selective. May participate in
CC the formation of the permeability transition pore complex (PTPC)
CC responsible for the release of mitochondrial products that
CC triggers apoptosis.
CC -!- SUBUNIT: Interacts with hexokinases (By similarity). Interacts
CC with BCL2L1. Interacts with BOP/C22orf29 (via BH3 domain).
CC Interacts with influenza A virus PB1-F2 protein. Interacts with
CC HK1. The HK1-VDAC1 complex interacts with ATF2 (By similarity).
CC -!- INTERACTION:
CC P19367:HK1; NbExp=2; IntAct=EBI-354158, EBI-713162;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane. Cell membrane.
CC -!- TISSUE SPECIFICITY: Heart, liver and skeletal muscle.
CC -!- DOMAIN: Consists mainly of a membrane-spanning beta-barrel formed
CC by 19 beta-strands. The helical N-terminus folds back into the
CC pore opening and plays a role in voltage-gated channel activity.
CC -!- SIMILARITY: Belongs to the eukaryotic mitochondrial porin family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/VDAC1ID50902ch5q31.html";
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DR EMBL; L06132; AAA61272.1; -; mRNA.
DR EMBL; AJ250032; CAB58127.1; -; Genomic_DNA.
DR EMBL; AJ250033; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250034; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250035; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250036; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250037; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250038; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250039; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AF151097; AAD54939.1; -; Genomic_DNA.
DR EMBL; AF151093; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AF151094; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AF151095; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AF151096; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AC005200; AAC24723.1; -; Genomic_DNA.
DR EMBL; AK122953; BAG53816.1; -; mRNA.
DR EMBL; AC008608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62281.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62282.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62283.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62285.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62286.1; -; Genomic_DNA.
DR EMBL; BC008482; AAH08482.1; -; mRNA.
DR EMBL; BC071168; AAH71168.1; -; mRNA.
DR EMBL; BC090042; AAH90042.1; -; mRNA.
DR PIR; A44422; MMHUP3.
DR RefSeq; NP_003365.1; NM_003374.2.
DR RefSeq; XP_005272132.1; XM_005272075.1.
DR UniGene; Hs.519320; -.
DR PDB; 2JK4; X-ray; 4.10 A; A=2-283.
DR PDB; 2K4T; NMR; -; A=1-283.
DR PDBsum; 2JK4; -.
DR PDBsum; 2K4T; -.
DR ProteinModelPortal; P21796; -.
DR SMR; P21796; 2-283.
DR DIP; DIP-32862N; -.
DR IntAct; P21796; 18.
DR MINT; MINT-5002499; -.
DR STRING; 9606.ENSP00000265333; -.
DR DrugBank; DB01375; Dihydroxyaluminium.
DR PhosphoSite; P21796; -.
DR DMDM; 130683; -.
DR DOSAC-COBS-2DPAGE; P21796; -.
DR OGP; P21796; -.
DR REPRODUCTION-2DPAGE; IPI00216308; -.
DR REPRODUCTION-2DPAGE; P21796; -.
DR UCD-2DPAGE; P21796; -.
DR PaxDb; P21796; -.
DR PeptideAtlas; P21796; -.
DR PRIDE; P21796; -.
DR DNASU; 7416; -.
DR Ensembl; ENST00000265333; ENSP00000265333; ENSG00000213585.
DR Ensembl; ENST00000395044; ENSP00000378484; ENSG00000213585.
DR Ensembl; ENST00000395047; ENSP00000378487; ENSG00000213585.
DR GeneID; 7416; -.
DR KEGG; hsa:7416; -.
DR UCSC; uc003kyp.2; human.
DR CTD; 7416; -.
DR GeneCards; GC05M133307; -.
DR H-InvDB; HIX0056260; -.
DR HGNC; HGNC:12669; VDAC1.
DR HPA; CAB005885; -.
DR MIM; 604492; gene+phenotype.
DR neXtProt; NX_P21796; -.
DR PharmGKB; PA37292; -.
DR eggNOG; NOG243169; -.
DR HOGENOM; HOG000188277; -.
DR HOVERGEN; HBG054036; -.
DR InParanoid; P21796; -.
DR KO; K05862; -.
DR OMA; YGLMFTE; -.
DR PhylomeDB; P21796; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR EvolutionaryTrace; P21796; -.
DR GeneWiki; VDAC1; -.
DR GenomeRNAi; 7416; -.
DR NextBio; 29038; -.
DR PRO; PR:P21796; -.
DR ArrayExpress; P21796; -.
DR Bgee; P21796; -.
DR CleanEx; HS_VDAC1; -.
DR Genevestigator; P21796; -.
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:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046930; C:pore complex; TAS:HGNC.
DR GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR GO; GO:0008308; F:voltage-gated anion channel activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0007270; P:neuron-neuron synaptic transmission; 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 3D-structure; Acetylation; Apoptosis; Cell membrane;
KW Complete proteome; Direct protein sequencing; Host-virus interaction;
KW Ion transport; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Phosphoprotein; Porin; Reference proteome; Transmembrane;
KW Transmembrane beta strand; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 283 Voltage-dependent anion-selective channel
FT protein 1.
FT /FTId=PRO_0000050499.
FT TRANSMEM 26 35 Beta stranded.
FT TRANSMEM 39 47 Beta stranded.
FT TRANSMEM 54 64 Beta stranded.
FT TRANSMEM 69 76 Beta stranded.
FT TRANSMEM 80 89 Beta stranded.
FT TRANSMEM 95 104 Beta stranded.
FT TRANSMEM 111 120 Beta stranded.
FT TRANSMEM 123 130 Beta stranded.
FT TRANSMEM 137 145 Beta stranded.
FT TRANSMEM 150 158 Beta stranded.
FT TRANSMEM 163 175 Beta stranded.
FT TRANSMEM 178 185 Beta stranded.
FT TRANSMEM 189 198 Beta stranded.
FT TRANSMEM 202 211 Beta stranded.
FT TRANSMEM 218 227 Beta stranded.
FT TRANSMEM 231 238 Beta stranded.
FT TRANSMEM 242 251 Beta stranded.
FT TRANSMEM 254 263 Beta stranded.
FT TRANSMEM 273 282 Beta stranded.
FT NP_BIND 242 244 NAD.
FT NP_BIND 260 264 NAD.
FT SITE 73 73 Involved in hexokinase binding (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 13 13 Phosphoserine (By similarity).
FT MOD_RES 20 20 N6-acetyllysine.
FT MOD_RES 67 67 Phosphotyrosine (By similarity).
FT MOD_RES 109 109 N6-acetyllysine (By similarity).
FT MOD_RES 252 252 N6-acetyllysine (By similarity).
FT MOD_RES 266 266 N6-acetyllysine.
FT CONFLICT 225 225 Y -> L (in Ref. 4; CAB58127).
FT TURN 7 10
FT STRAND 26 33
FT TURN 36 38
FT STRAND 40 51
FT STRAND 55 62
FT STRAND 66 76
FT TURN 77 79
FT STRAND 80 88
FT STRAND 95 103
FT TURN 105 107
FT STRAND 110 119
FT STRAND 124 135
FT STRAND 137 146
FT STRAND 149 158
FT TURN 159 162
FT STRAND 167 174
FT STRAND 176 185
FT TURN 186 188
FT STRAND 189 196
FT STRAND 203 211
FT STRAND 217 228
FT STRAND 231 241
FT STRAND 243 250
FT STRAND 252 254
FT STRAND 256 264
FT HELIX 268 270
FT STRAND 274 282
SQ SEQUENCE 283 AA; 30773 MW; 89BA3378B04020D5 CRC64;
MAVPPTYADL GKSARDVFTK GYGFGLIKLD LKTKSENGLE FTSSGSANTE TTKVTGSLET
KYRWTEYGLT FTEKWNTDNT LGTEITVEDQ LARGLKLTFD SSFSPNTGKK NAKIKTGYKR
EHINLGCDMD FDIAGPSIRG ALVLGYEGWL AGYQMNFETA KSRVTQSNFA VGYKTDEFQL
HTNVNDGTEF GGSIYQKVNK KLETAVNLAW TAGNSNTRFG IAAKYQIDPD ACFSAKVNNS
SLIGLGYTQT LKPGIKLTLS ALLDGKNVNA GGHKLGLGLE FQA
//
ID VDAC1_HUMAN Reviewed; 283 AA.
AC P21796; B3KVK4; D3DQ93; Q5FVE7; Q9UIQ5; Q9UPL0;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Voltage-dependent anion-selective channel protein 1;
DE Short=VDAC-1;
DE Short=hVDAC1;
DE AltName: Full=Outer mitochondrial membrane protein porin 1;
DE AltName: Full=Plasmalemmal porin;
DE AltName: Full=Porin 31HL;
DE AltName: Full=Porin 31HM;
GN Name=VDAC1; Synonyms=VDAC;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pituitary;
RA Blachly-Dyson E., Forte M.A.;
RT "Cloning of human VDAC cDNA.";
RL Biophys. J. 59:216A-216A(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [GENOMIC DNA].
RX PubMed=10772903; DOI=10.1006/bbrc.2000.2487;
RA Messina A., Guarino F., Oliva M., van den Heuvel L.P., Smeitink J.,
RA De Pinto V.;
RT "Characterization of the human porin isoform 1 (HVDAC1) gene by
RT amplification on the whole human genome: a tool for porin deficiency
RT analysis.";
RL Biochem. Biophys. Res. Commun. 270:787-792(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 2-283.
RC TISSUE=Lymphocyte;
RX PubMed=2559745;
RA Kayser H., Kratzin H.D., Thinnes F.P., Goetz H., Schmidt W.E.,
RA Eckart K., Hilschmann N.;
RT "Identification of human porins. II. Characterization and primary
RT structure of a 31-lDa porin from human B lymphocytes (Porin 31HL).";
RL Biol. Chem. Hoppe-Seyler 370:1265-1278(1989).
RN [10]
RP PROTEIN SEQUENCE OF 2-283.
RC TISSUE=Skeletal muscle;
RX PubMed=1657034;
RA Juergens L., Ilsemann P., Kratzin H.D., Hesse D., Eckart K.,
RA Thinnes F.P., Hilschmann N.;
RT "Studies on human porin. IV. The primary structures of 'Porin 31HM'
RT purified from human skeletal muscle membranes and of 'Porin 31HL'
RT derived from human B lymphocyte membranes are identical.";
RL Biol. Chem. Hoppe-Seyler 372:455-463(1991).
RN [11]
RP PROTEIN SEQUENCE OF 2-283.
RC TISSUE=B-cell;
RA Hein A., Kiafard Z., Hesse D., Hesse J.-O., Zimmermann B.,
RA Kratzin H.D., Schulz H., Reiss J., Thinnes F.P., Goetz H.,
RA Hilschmann N.;
RL Submitted (DEC-1997) to UniProtKB.
RN [12]
RP PROTEIN SEQUENCE OF 2-12; 21-61; 64-74; 94-110; 121-139; 162-174;
RP 225-236 AND 257-274, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 75-93; 175-197 AND 201-218, AND MASS 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 [14]
RP MUTAGENESIS.
RX PubMed=7685903; DOI=10.1073/pnas.90.12.5446;
RA Thomas L., Blachly-Dyson E., Colombini M., Forte M.A.;
RT "Mapping of residues forming the voltage sensor of the voltage-
RT dependent anion-selective channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5446-5449(1993).
RN [15]
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 [16]
RP CHARACTERIZATION, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=10661876; DOI=10.1515/BC.1999.189;
RA Stadtmueller U., Eben-Brunnen J., Schmid A., Hesse D., Klebert S.,
RA Kratzin H.D., Hesse J., Zimmermann B., Reymann S., Thinnes F.P.,
RA Benz R., Goetz H., Hilschmann N.;
RT "Mitochondria-derived and extra-mitochondrial human type-1 porin are
RT identical as revealed by amino acid sequencing and
RT electrophysiological characterisation.";
RL Biol. Chem. 380:1461-1466(1999).
RN [17]
RP FUNCTION.
RX PubMed=11845315; DOI=10.1007/s004240100656;
RA Thinnes F.P., Walter G., Hellmann K.P., Hellmann T., Merker R.,
RA Kiafard Z., Eben-Brunnen J., Schwarzer C., Goetz H., Hilschmann N.;
RT "Gadolinium as an opener of the outwardly rectifying Cl(-) channel
RT (ORCC). Is there relevance for cystic fibrosis therapy?";
RL Pflugers Arch. 443:S111-S116(2001).
RN [18]
RP FUNCTION IN APOPTOSIS.
RX PubMed=15033708; DOI=10.1196/annals.1299.022;
RA Verrier F., Mignotte B., Jan G., Brenner C.;
RT "Study of PTPC composition during apoptosis for identification of
RT viral protein target.";
RL Ann. N. Y. Acad. Sci. 1010:126-142(2003).
RN [19]
RP INTERACTION WITH INFLUENZA A VIRUS PB1-F2.
RX PubMed=16201016; DOI=10.1371/journal.ppat.0010004;
RA Zamarin D., Garcia-Sastre A., Xiao X., Wang R., Palese P.;
RT "Influenza virus PB1-F2 protein induces cell death through
RT mitochondrial ANT3 and VDAC1.";
RL PLoS Pathog. 1:40-54(2005).
RN [20]
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 [21]
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 [22]
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 [23]
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 [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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 [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-20 AND LYS-266, AND MASS
RP 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 [26]
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 [27]
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 [28]
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).
RN [29]
RP INTERACTION WITH ATF2 AND HK1.
RX PubMed=22304920; DOI=10.1016/j.cell.2012.01.016;
RA Lau E., Kluger H., Varsano T., Lee K., Scheffler I., Rimm D.L.,
RA Ideker T., Ronai Z.A.;
RT "PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while
RT blocking its apoptotic function at mitochondria.";
RL Cell 148:543-555(2012).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP INTERACTION WITH BOP/C22ORF29.
RX PubMed=23055042; DOI=10.1007/s13238-012-2069-7;
RA Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q.,
RA Pan L., Tang H.;
RT "Human Bop is a novel BH3-only member of the Bcl-2 protein family.";
RL Protein Cell 3:790-801(2012).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (4.1 ANGSTROMS) OF 2-283, AND STRUCTURE BY NMR.
RX PubMed=18832158; DOI=10.1073/pnas.0808115105;
RA Bayrhuber M., Meins T., Habeck M., Becker S., Giller K., Villinger S.,
RA Vonrhein C., Griesinger C., Zweckstetter M., Zeth K.;
RT "Structure of the human voltage-dependent anion channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:15370-15375(2008).
RN [33]
RP STRUCTURE BY NMR, FUNCTION, INTERACTION WITH BCL2L1, AND NADH-BINDING.
RX PubMed=18755977; DOI=10.1126/science.1161302;
RA Hiller S., Garces R.G., Malia T.J., Orekhov V.Y., Colombini M.,
RA Wagner G.;
RT "Solution structure of the integral human membrane protein VDAC-1 in
RT detergent micelles.";
RL Science 321:1206-1210(2008).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane
CC and also the plasma membrane. The channel at the outer
CC mitochondrial membrane allows diffusion of small hydrophilic
CC molecules; in the plasma membrane it is involved in cell volume
CC regulation and apoptosis. It adopts an open conformation at low or
CC zero membrane potential and a closed conformation at potentials
CC above 30-40 mV. The open state has a weak anion selectivity
CC whereas the closed state is cation-selective. May participate in
CC the formation of the permeability transition pore complex (PTPC)
CC responsible for the release of mitochondrial products that
CC triggers apoptosis.
CC -!- SUBUNIT: Interacts with hexokinases (By similarity). Interacts
CC with BCL2L1. Interacts with BOP/C22orf29 (via BH3 domain).
CC Interacts with influenza A virus PB1-F2 protein. Interacts with
CC HK1. The HK1-VDAC1 complex interacts with ATF2 (By similarity).
CC -!- INTERACTION:
CC P19367:HK1; NbExp=2; IntAct=EBI-354158, EBI-713162;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane. Cell membrane.
CC -!- TISSUE SPECIFICITY: Heart, liver and skeletal muscle.
CC -!- DOMAIN: Consists mainly of a membrane-spanning beta-barrel formed
CC by 19 beta-strands. The helical N-terminus folds back into the
CC pore opening and plays a role in voltage-gated channel activity.
CC -!- SIMILARITY: Belongs to the eukaryotic mitochondrial porin family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/VDAC1ID50902ch5q31.html";
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DR EMBL; L06132; AAA61272.1; -; mRNA.
DR EMBL; AJ250032; CAB58127.1; -; Genomic_DNA.
DR EMBL; AJ250033; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250034; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250035; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250036; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250037; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250038; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AJ250039; CAB58127.1; JOINED; Genomic_DNA.
DR EMBL; AF151097; AAD54939.1; -; Genomic_DNA.
DR EMBL; AF151093; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AF151094; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AF151095; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AF151096; AAD54939.1; JOINED; Genomic_DNA.
DR EMBL; AC005200; AAC24723.1; -; Genomic_DNA.
DR EMBL; AK122953; BAG53816.1; -; mRNA.
DR EMBL; AC008608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62281.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62282.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62283.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62285.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62286.1; -; Genomic_DNA.
DR EMBL; BC008482; AAH08482.1; -; mRNA.
DR EMBL; BC071168; AAH71168.1; -; mRNA.
DR EMBL; BC090042; AAH90042.1; -; mRNA.
DR PIR; A44422; MMHUP3.
DR RefSeq; NP_003365.1; NM_003374.2.
DR RefSeq; XP_005272132.1; XM_005272075.1.
DR UniGene; Hs.519320; -.
DR PDB; 2JK4; X-ray; 4.10 A; A=2-283.
DR PDB; 2K4T; NMR; -; A=1-283.
DR PDBsum; 2JK4; -.
DR PDBsum; 2K4T; -.
DR ProteinModelPortal; P21796; -.
DR SMR; P21796; 2-283.
DR DIP; DIP-32862N; -.
DR IntAct; P21796; 18.
DR MINT; MINT-5002499; -.
DR STRING; 9606.ENSP00000265333; -.
DR DrugBank; DB01375; Dihydroxyaluminium.
DR PhosphoSite; P21796; -.
DR DMDM; 130683; -.
DR DOSAC-COBS-2DPAGE; P21796; -.
DR OGP; P21796; -.
DR REPRODUCTION-2DPAGE; IPI00216308; -.
DR REPRODUCTION-2DPAGE; P21796; -.
DR UCD-2DPAGE; P21796; -.
DR PaxDb; P21796; -.
DR PeptideAtlas; P21796; -.
DR PRIDE; P21796; -.
DR DNASU; 7416; -.
DR Ensembl; ENST00000265333; ENSP00000265333; ENSG00000213585.
DR Ensembl; ENST00000395044; ENSP00000378484; ENSG00000213585.
DR Ensembl; ENST00000395047; ENSP00000378487; ENSG00000213585.
DR GeneID; 7416; -.
DR KEGG; hsa:7416; -.
DR UCSC; uc003kyp.2; human.
DR CTD; 7416; -.
DR GeneCards; GC05M133307; -.
DR H-InvDB; HIX0056260; -.
DR HGNC; HGNC:12669; VDAC1.
DR HPA; CAB005885; -.
DR MIM; 604492; gene+phenotype.
DR neXtProt; NX_P21796; -.
DR PharmGKB; PA37292; -.
DR eggNOG; NOG243169; -.
DR HOGENOM; HOG000188277; -.
DR HOVERGEN; HBG054036; -.
DR InParanoid; P21796; -.
DR KO; K05862; -.
DR OMA; YGLMFTE; -.
DR PhylomeDB; P21796; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR EvolutionaryTrace; P21796; -.
DR GeneWiki; VDAC1; -.
DR GenomeRNAi; 7416; -.
DR NextBio; 29038; -.
DR PRO; PR:P21796; -.
DR ArrayExpress; P21796; -.
DR Bgee; P21796; -.
DR CleanEx; HS_VDAC1; -.
DR Genevestigator; P21796; -.
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:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046930; C:pore complex; TAS:HGNC.
DR GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR GO; GO:0008308; F:voltage-gated anion channel activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0007270; P:neuron-neuron synaptic transmission; 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 3D-structure; Acetylation; Apoptosis; Cell membrane;
KW Complete proteome; Direct protein sequencing; Host-virus interaction;
KW Ion transport; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Phosphoprotein; Porin; Reference proteome; Transmembrane;
KW Transmembrane beta strand; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 283 Voltage-dependent anion-selective channel
FT protein 1.
FT /FTId=PRO_0000050499.
FT TRANSMEM 26 35 Beta stranded.
FT TRANSMEM 39 47 Beta stranded.
FT TRANSMEM 54 64 Beta stranded.
FT TRANSMEM 69 76 Beta stranded.
FT TRANSMEM 80 89 Beta stranded.
FT TRANSMEM 95 104 Beta stranded.
FT TRANSMEM 111 120 Beta stranded.
FT TRANSMEM 123 130 Beta stranded.
FT TRANSMEM 137 145 Beta stranded.
FT TRANSMEM 150 158 Beta stranded.
FT TRANSMEM 163 175 Beta stranded.
FT TRANSMEM 178 185 Beta stranded.
FT TRANSMEM 189 198 Beta stranded.
FT TRANSMEM 202 211 Beta stranded.
FT TRANSMEM 218 227 Beta stranded.
FT TRANSMEM 231 238 Beta stranded.
FT TRANSMEM 242 251 Beta stranded.
FT TRANSMEM 254 263 Beta stranded.
FT TRANSMEM 273 282 Beta stranded.
FT NP_BIND 242 244 NAD.
FT NP_BIND 260 264 NAD.
FT SITE 73 73 Involved in hexokinase binding (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 13 13 Phosphoserine (By similarity).
FT MOD_RES 20 20 N6-acetyllysine.
FT MOD_RES 67 67 Phosphotyrosine (By similarity).
FT MOD_RES 109 109 N6-acetyllysine (By similarity).
FT MOD_RES 252 252 N6-acetyllysine (By similarity).
FT MOD_RES 266 266 N6-acetyllysine.
FT CONFLICT 225 225 Y -> L (in Ref. 4; CAB58127).
FT TURN 7 10
FT STRAND 26 33
FT TURN 36 38
FT STRAND 40 51
FT STRAND 55 62
FT STRAND 66 76
FT TURN 77 79
FT STRAND 80 88
FT STRAND 95 103
FT TURN 105 107
FT STRAND 110 119
FT STRAND 124 135
FT STRAND 137 146
FT STRAND 149 158
FT TURN 159 162
FT STRAND 167 174
FT STRAND 176 185
FT TURN 186 188
FT STRAND 189 196
FT STRAND 203 211
FT STRAND 217 228
FT STRAND 231 241
FT STRAND 243 250
FT STRAND 252 254
FT STRAND 256 264
FT HELIX 268 270
FT STRAND 274 282
SQ SEQUENCE 283 AA; 30773 MW; 89BA3378B04020D5 CRC64;
MAVPPTYADL GKSARDVFTK GYGFGLIKLD LKTKSENGLE FTSSGSANTE TTKVTGSLET
KYRWTEYGLT FTEKWNTDNT LGTEITVEDQ LARGLKLTFD SSFSPNTGKK NAKIKTGYKR
EHINLGCDMD FDIAGPSIRG ALVLGYEGWL AGYQMNFETA KSRVTQSNFA VGYKTDEFQL
HTNVNDGTEF GGSIYQKVNK KLETAVNLAW TAGNSNTRFG IAAKYQIDPD ACFSAKVNNS
SLIGLGYTQT LKPGIKLTLS ALLDGKNVNA GGHKLGLGLE FQA
//
MIM
604492
*RECORD*
*FIELD* NO
604492
*FIELD* TI
*604492 VOLTAGE-DEPENDENT ANION CHANNEL 1; VDAC1
;;PORIN;;
OMP2, YEAST, HUMAN COMPLEMENT OF
read more*FIELD* TX
DESCRIPTION
The voltage-dependent anion channel (VDAC) of the outer mitochondrial
membrane is a small, abundant outer membrane pore-forming protein found
in the outer membranes of all eukaryotic mitochondria. The VDAC protein
is thought to form the major pathway for movement of adenine nucleotides
through the outer membrane and to be the mitochondrial binding site for
hexokinase (see 142600) and glycerol kinase (GK; 300474) (summary by
Blachly-Dyson et al., 1993). At low transmembrane voltage, VDAC is open
for anions such as phosphate, chloride, and adenine nucleotides. At
higher transmembrane voltage, VDAC functions as a selective channel for
cations and uncharged molecules. These features make VDAC likely to play
a role in mitochondrial energy metabolism (summary by Huizing et al.,
1996).
CLONING
Blachly-Dyson et al. (1993) identified and characterized 2 human cDNAs
encoding VDAC homologs, which they called HVDAC1 and HVDAC2 (VDAC2;
193245). Each human cDNA was expressed in essentially all human cell
lines and tissues examined.
Huizing et al. (1998) studied by Northern and Western blot analyses the
human tissue distribution of mitochondrial transmembrane metabolite
carriers. They found that VDAC1 mRNA has a ubiquitous distribution, with
most pronounced expression in heart, liver, and skeletal muscle, whereas
the VDAC2 (193245) isoform appears to be expressed only in the heart.
GENE STRUCTURE
Messina et al. (2000) determined that the VDAC1 gene contains 9 exons
and spans about 33 kb. The first exon is noncoding. The promoter region
lacks a canonical TATA box, but it is GC rich and has a sterol repressor
element and binding sites for SRY (480000) and NRF2 (NFE2L2; 600492).
MAPPING
Blachly-Dyson et al. (1994) had mapped the VDAC1 to chromosome Xq13-q21;
however, screening the human chromosome X cosmid library by Messina et
al. (1999) resulted in the isolation only of processed pseudogenes,
finely mapped to Xq22 and Xp11.2. By fluorescence in situ hybridization
of a pool of 3 probes designed to VDAC1, Messina et al. (1999) mapped
the VDAC1 gene to chromosome 5q31. The homologous mouse gene resides on
proximal chromosome 11, in a region showing homology of synteny with
human 5q31.
GENE FUNCTION
Blachly-Dyson et al. (1993) found that mitochondria expressing VDAC1
were capable of specifically binding hexokinase, whereas mitochondria
expressing VDAC2 only bound hexokinase at background levels. They
expressed the 2 human VDAC isoforms in yeast lacking the endogenous VDAC
gene. The human proteins isolated from yeast mitochondria formed
channels with the characteristics expected of VDAC when incorporated
into planar lipid bilayers. Furthermore, expression of the human
proteins in the deficient strains complemented phenotypic defects
associated with elimination of the endogenous yeast VDAC gene. The
mutant of S. cerevisiae was known as omp2.
The existence of multiple genes encoding VDAC isoforms in mammals was
not unexpected. Antibodies generated to VDAC1 purified from mitochondria
appeared to crossreact immunocytochemically with the plasma membrane.
Biochemical and physiologic studies had also suggested that VDAC-like
proteins may be present in the plasma membrane. Lewis et al. (1994) used
post-embedding immunolabeling to investigate the presence of VDAC in the
semitendinosus muscle of the cane toad Bufo marinus and found labeling
not only of the outer mitochondrial membrane but also of the
sarcoplasmic reticulum, indicating the presence of a VDAC-like protein
in the sarcoplasmic reticulum. Lewis et al. (1994) suggested that the
various VDAC isoforms may differ in their subcellular localization or
cell type and developmental expression pattern.
Bathori et al. (1999) used biochemical and electrophysiologic techniques
to detect and characterize porin, or VDAC1, within isolated caveolae and
caveolae-like domains. Porin purified from caveolae had molecular (i.e.,
immunologic reactivity and chromatographic behavior) and
electrophysiologic properties indistinguishable from those of
mitochondrial porin. Thus, Bathori et al. (1999) concluded that VDAC1 is
able to be incorporated into both the plasma membrane and the
mitochondrial outer membrane.
During transduction of an apoptotic signal into the cell, there is an
alteration in the permeability of the membranes of the cell's
mitochondria, which causes the translocation of the apoptogenic protein
cytochrome c into the cytoplasm, which in turn activates death-driving
proteolytic proteins known as caspases (see 147678). The BCL2 family of
proteins, whose members may be antiapoptotic or proapoptotic, regulates
cell death by controlling this mitochondrial membrane permeability
during apoptosis. Shimizu et al. (1999) created liposomes that carried
the mitochondrial porin channel VDAC to show that the recombinant
proapoptotic proteins Bax (600040) and Bak (600516) accelerate the
opening of VDAC, whereas the antiapoptotic protein BCLXL (600039) closes
VDAC by binding to it directly. Bax and Bak allow cytochrome c to pass
through VDAC out of liposomes, but passage is prevented by BCLXL. In
agreement with this, VDAC1-deficient mitochondria from a mutant yeast
did not exhibit a Bax/Bak-induced loss in membrane potential and
cytochrome c release, both of which were inhibited by BCLXL. Shimizu et
al. (1999) concluded that the BCL2 family of proteins bind to the VDAC
in order to regulate the mitochondrial membrane potential and the
release of cytochrome c during apoptosis.
Geisler et al. (2010) identified VDAC1 as a target for parkin (PARK2;
602544)-mediated polyubiquitination and mitophagy in mitochondria
damaged by dissipation of the membrane potential. Parkinson disease
(600116)-associated PARK2 mutations interrupted this process, suggesting
a role for interference of mitophagy in the pathogenesis of Parkinson
disease.
BIOCHEMICAL FEATURES
- Crystal Structure
Hiller et al. (2008) presented the nuclear magnetic resonance solutions
structure of recombinant human VDAC1 reconstituted in detergent
micelles. It forms a 19-stranded beta barrel with the first and last
strand parallel. The hydrophobic outside perimeter of the barrel is
covered by detergent molecules in a beltlike fashion. In the presence of
cholesterol, recombinant VDAC1 can form voltage-gated channels in
phospholipid bilayers similar to those of the native protein. NMR
measurements revealed the binding sites of VDAC1 for the BCL2 protein
BCLXL, for reduced beta-nicotinamide adenine dinucleotide, and for
cholesterol. BCLXL interacts with the VDAC barrel laterally at strands
17 and 18.
ANIMAL MODEL
Anflous-Pharayra et al. (2007) found that Vdac1 -/- mice were viable and
exhibited mild growth retardation. Soleus muscle from Vdac1 -/- mice
showed reduced hexokinase-2 (HK2; 601125) protein content and activity
and impaired glucose tolerance, but normal exercise tolerance, compared
with wildtype.
*FIELD* RF
1. Anflous-Pharayra, K.; Cai, Z.-J.; Craigen, W. J.: VDAC1 serves
as a mitochondrial binding site for hexokinase in oxidative muscles. Biochim.
Biphys. Acta 1767: 136-142, 2007.
2. Bathori, G.; Parolini, I.; Tombola, F.; Szabo, I.; Messina, A.;
Oliva, M.; De Pinto, V.; Lisanti, M.; Sargiacomo, M.; Zoratti, M.
: Porin is present in the plasma membrane where it is concentrated
in caveolae and caveolae-related domains. J. Biol. Chem. 274: 29607-29612,
1999.
3. 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.
4. 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.
5. Geisler, S.; Holmstrom, K. M.; Skujat, D.; Fiesel, F. C.; Rothfuss,
O. C.; Kahle, P. J.; Springer, W.: PINK1/Parkin-mediated mitophagy
is dependent on VDAC1 and p62/SQSTM1. Nature Cell Biol. 12: 119-131,
2010.
6. Hiller, S.; Garces, R. G.; Malia, T. J.; Orekhov, V. Y.; Colombini,
M.; Wagner, G.: Solution structure of the integral human membrane
protein VDAC-1 in detergent micelles. Science 321: 1206-1210, 2008.
7. Huizing, M.; Ruitenbeek, W.; Thinnes, F. P.; DePinto, V.; Wendel,
U.; Trijbels, F. J. M.; Smit, L. M. E.; Ter Laak, H. J.; Van Den Heuvel,
L. P.: Deficiency of the voltage-dependent anion channel: a novel
cause of mitochondriopathy. Pediat. Res. 39: 760-765, 1996.
8. 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.
9. Lewis, T. M.; Roberts, M. L.; Bretag, A. H.: Immunolabelling for
VDAC, the mitochondrial voltage-dependent anion channel, on sarcoplasmic
reticulum from amphibian skeletal muscle. Neurosci. Lett. 181: 83-86,
1994.
10. Messina, A.; Guarino, F.; Oliva, M.; van den Heuvel, L. P.; Smeitink,
J.; De Pinto, V.: Characterization of the human porin isoform 1 (HVDAC1)
gene by amplification on the whole human genome: a tool for porin
deficiency analysis. Biochem. Biophys. Res. Commun. 270: 787-792,
2000.
11. 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.
12. Shimizu, S.; Narita, M.; Tsujimoto, Y.: Bcl-2 family proteins
regulate the release of apoptogenic cytochrome c by the mitochondrial
channel VDAC. Nature 399: 483-487, 1999. Note: Erratum: Nature 407:
767 only, 2000.
*FIELD* CN
Patricia A. Hartz - updated: 2/21/2012
Cassandra L. Kniffin - updated: 4/5/2010
Ada Hamosh - updated: 9/24/2008
*FIELD* CD
Ada Hamosh: 2/2/2000
*FIELD* ED
terry: 10/03/2012
carol: 3/9/2012
ckniffin: 3/8/2012
mgross: 3/6/2012
terry: 2/21/2012
carol: 3/15/2011
wwang: 4/12/2010
ckniffin: 4/5/2010
alopez: 9/29/2008
alopez: 9/24/2008
terry: 9/24/2008
joanna: 3/17/2004
joanna: 1/22/2004
joanna: 10/17/2001
alopez: 2/2/2000
*RECORD*
*FIELD* NO
604492
*FIELD* TI
*604492 VOLTAGE-DEPENDENT ANION CHANNEL 1; VDAC1
;;PORIN;;
OMP2, YEAST, HUMAN COMPLEMENT OF
read more*FIELD* TX
DESCRIPTION
The voltage-dependent anion channel (VDAC) of the outer mitochondrial
membrane is a small, abundant outer membrane pore-forming protein found
in the outer membranes of all eukaryotic mitochondria. The VDAC protein
is thought to form the major pathway for movement of adenine nucleotides
through the outer membrane and to be the mitochondrial binding site for
hexokinase (see 142600) and glycerol kinase (GK; 300474) (summary by
Blachly-Dyson et al., 1993). At low transmembrane voltage, VDAC is open
for anions such as phosphate, chloride, and adenine nucleotides. At
higher transmembrane voltage, VDAC functions as a selective channel for
cations and uncharged molecules. These features make VDAC likely to play
a role in mitochondrial energy metabolism (summary by Huizing et al.,
1996).
CLONING
Blachly-Dyson et al. (1993) identified and characterized 2 human cDNAs
encoding VDAC homologs, which they called HVDAC1 and HVDAC2 (VDAC2;
193245). Each human cDNA was expressed in essentially all human cell
lines and tissues examined.
Huizing et al. (1998) studied by Northern and Western blot analyses the
human tissue distribution of mitochondrial transmembrane metabolite
carriers. They found that VDAC1 mRNA has a ubiquitous distribution, with
most pronounced expression in heart, liver, and skeletal muscle, whereas
the VDAC2 (193245) isoform appears to be expressed only in the heart.
GENE STRUCTURE
Messina et al. (2000) determined that the VDAC1 gene contains 9 exons
and spans about 33 kb. The first exon is noncoding. The promoter region
lacks a canonical TATA box, but it is GC rich and has a sterol repressor
element and binding sites for SRY (480000) and NRF2 (NFE2L2; 600492).
MAPPING
Blachly-Dyson et al. (1994) had mapped the VDAC1 to chromosome Xq13-q21;
however, screening the human chromosome X cosmid library by Messina et
al. (1999) resulted in the isolation only of processed pseudogenes,
finely mapped to Xq22 and Xp11.2. By fluorescence in situ hybridization
of a pool of 3 probes designed to VDAC1, Messina et al. (1999) mapped
the VDAC1 gene to chromosome 5q31. The homologous mouse gene resides on
proximal chromosome 11, in a region showing homology of synteny with
human 5q31.
GENE FUNCTION
Blachly-Dyson et al. (1993) found that mitochondria expressing VDAC1
were capable of specifically binding hexokinase, whereas mitochondria
expressing VDAC2 only bound hexokinase at background levels. They
expressed the 2 human VDAC isoforms in yeast lacking the endogenous VDAC
gene. The human proteins isolated from yeast mitochondria formed
channels with the characteristics expected of VDAC when incorporated
into planar lipid bilayers. Furthermore, expression of the human
proteins in the deficient strains complemented phenotypic defects
associated with elimination of the endogenous yeast VDAC gene. The
mutant of S. cerevisiae was known as omp2.
The existence of multiple genes encoding VDAC isoforms in mammals was
not unexpected. Antibodies generated to VDAC1 purified from mitochondria
appeared to crossreact immunocytochemically with the plasma membrane.
Biochemical and physiologic studies had also suggested that VDAC-like
proteins may be present in the plasma membrane. Lewis et al. (1994) used
post-embedding immunolabeling to investigate the presence of VDAC in the
semitendinosus muscle of the cane toad Bufo marinus and found labeling
not only of the outer mitochondrial membrane but also of the
sarcoplasmic reticulum, indicating the presence of a VDAC-like protein
in the sarcoplasmic reticulum. Lewis et al. (1994) suggested that the
various VDAC isoforms may differ in their subcellular localization or
cell type and developmental expression pattern.
Bathori et al. (1999) used biochemical and electrophysiologic techniques
to detect and characterize porin, or VDAC1, within isolated caveolae and
caveolae-like domains. Porin purified from caveolae had molecular (i.e.,
immunologic reactivity and chromatographic behavior) and
electrophysiologic properties indistinguishable from those of
mitochondrial porin. Thus, Bathori et al. (1999) concluded that VDAC1 is
able to be incorporated into both the plasma membrane and the
mitochondrial outer membrane.
During transduction of an apoptotic signal into the cell, there is an
alteration in the permeability of the membranes of the cell's
mitochondria, which causes the translocation of the apoptogenic protein
cytochrome c into the cytoplasm, which in turn activates death-driving
proteolytic proteins known as caspases (see 147678). The BCL2 family of
proteins, whose members may be antiapoptotic or proapoptotic, regulates
cell death by controlling this mitochondrial membrane permeability
during apoptosis. Shimizu et al. (1999) created liposomes that carried
the mitochondrial porin channel VDAC to show that the recombinant
proapoptotic proteins Bax (600040) and Bak (600516) accelerate the
opening of VDAC, whereas the antiapoptotic protein BCLXL (600039) closes
VDAC by binding to it directly. Bax and Bak allow cytochrome c to pass
through VDAC out of liposomes, but passage is prevented by BCLXL. In
agreement with this, VDAC1-deficient mitochondria from a mutant yeast
did not exhibit a Bax/Bak-induced loss in membrane potential and
cytochrome c release, both of which were inhibited by BCLXL. Shimizu et
al. (1999) concluded that the BCL2 family of proteins bind to the VDAC
in order to regulate the mitochondrial membrane potential and the
release of cytochrome c during apoptosis.
Geisler et al. (2010) identified VDAC1 as a target for parkin (PARK2;
602544)-mediated polyubiquitination and mitophagy in mitochondria
damaged by dissipation of the membrane potential. Parkinson disease
(600116)-associated PARK2 mutations interrupted this process, suggesting
a role for interference of mitophagy in the pathogenesis of Parkinson
disease.
BIOCHEMICAL FEATURES
- Crystal Structure
Hiller et al. (2008) presented the nuclear magnetic resonance solutions
structure of recombinant human VDAC1 reconstituted in detergent
micelles. It forms a 19-stranded beta barrel with the first and last
strand parallel. The hydrophobic outside perimeter of the barrel is
covered by detergent molecules in a beltlike fashion. In the presence of
cholesterol, recombinant VDAC1 can form voltage-gated channels in
phospholipid bilayers similar to those of the native protein. NMR
measurements revealed the binding sites of VDAC1 for the BCL2 protein
BCLXL, for reduced beta-nicotinamide adenine dinucleotide, and for
cholesterol. BCLXL interacts with the VDAC barrel laterally at strands
17 and 18.
ANIMAL MODEL
Anflous-Pharayra et al. (2007) found that Vdac1 -/- mice were viable and
exhibited mild growth retardation. Soleus muscle from Vdac1 -/- mice
showed reduced hexokinase-2 (HK2; 601125) protein content and activity
and impaired glucose tolerance, but normal exercise tolerance, compared
with wildtype.
*FIELD* RF
1. Anflous-Pharayra, K.; Cai, Z.-J.; Craigen, W. J.: VDAC1 serves
as a mitochondrial binding site for hexokinase in oxidative muscles. Biochim.
Biphys. Acta 1767: 136-142, 2007.
2. Bathori, G.; Parolini, I.; Tombola, F.; Szabo, I.; Messina, A.;
Oliva, M.; De Pinto, V.; Lisanti, M.; Sargiacomo, M.; Zoratti, M.
: Porin is present in the plasma membrane where it is concentrated
in caveolae and caveolae-related domains. J. Biol. Chem. 274: 29607-29612,
1999.
3. 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.
4. 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.
5. Geisler, S.; Holmstrom, K. M.; Skujat, D.; Fiesel, F. C.; Rothfuss,
O. C.; Kahle, P. J.; Springer, W.: PINK1/Parkin-mediated mitophagy
is dependent on VDAC1 and p62/SQSTM1. Nature Cell Biol. 12: 119-131,
2010.
6. Hiller, S.; Garces, R. G.; Malia, T. J.; Orekhov, V. Y.; Colombini,
M.; Wagner, G.: Solution structure of the integral human membrane
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*FIELD* CN
Patricia A. Hartz - updated: 2/21/2012
Cassandra L. Kniffin - updated: 4/5/2010
Ada Hamosh - updated: 9/24/2008
*FIELD* CD
Ada Hamosh: 2/2/2000
*FIELD* ED
terry: 10/03/2012
carol: 3/9/2012
ckniffin: 3/8/2012
mgross: 3/6/2012
terry: 2/21/2012
carol: 3/15/2011
wwang: 4/12/2010
ckniffin: 4/5/2010
alopez: 9/29/2008
alopez: 9/24/2008
terry: 9/24/2008
joanna: 3/17/2004
joanna: 1/22/2004
joanna: 10/17/2001
alopez: 2/2/2000