Full text data of VDAC3
VDAC3
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Voltage-dependent anion-selective channel protein 3; VDAC-3; hVDAC3 (Outer mitochondrial membrane protein porin 3)
Voltage-dependent anion-selective channel protein 3; VDAC-3; hVDAC3 (Outer mitochondrial membrane protein porin 3)
Comments
Isoform Q9Y277-2 was detected.
Isoform Q9Y277-2 was detected.
UniProt
Q9Y277
ID VDAC3_HUMAN Reviewed; 283 AA.
AC Q9Y277; Q9UIS0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 119.
DE RecName: Full=Voltage-dependent anion-selective channel protein 3;
DE Short=VDAC-3;
DE Short=hVDAC3;
DE AltName: Full=Outer mitochondrial membrane protein porin 3;
GN Name=VDAC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9781040; DOI=10.1038/sj.ejhg.5200198;
RA Rahmani Z., Maunoury C., Siddiqui A.;
RT "Isolation of a novel human voltage-dependent anion channel gene.";
RL Eur. J. Hum. Genet. 6:337-340(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-
RT length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-253.
RX PubMed=10501981; DOI=10.1007/s003359901158;
RA Decker W.K., Bowles K.R., Schatte E.C., Towbin J.A., Craigen W.J.;
RT "Revised fine mapping of the human voltage-dependent anion channel
RT loci by radiation hybrid analysis.";
RL Mamm. Genome 10:1041-1042(1999).
RN [5]
RP ALTERNATIVE SPLICING.
RX PubMed=10833333; DOI=10.1006/mgme.2000.2987;
RA Decker W.K., Craigen W.J.;
RT "The tissue-specific, alternatively spliced single ATG exon of the
RT type 3 voltage-dependent anion channel gene does not create a
RT truncated protein isoform in vivo.";
RL Mol. Genet. Metab. 70:69-74(2000).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT CYS-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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-20 AND LYS-90, 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
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).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane
CC that allows diffusion of small hydrophilic molecules (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y277-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y277-2; Sequence=VSP_005079;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest in testis.
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 -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U90943; AAB93872.1; -; mRNA.
DR EMBL; AF038962; AAC39876.1; -; mRNA.
DR EMBL; BC056870; AAH56870.1; -; mRNA.
DR EMBL; AH008073; AAD49610.1; -; Genomic_DNA.
DR RefSeq; NP_001129166.1; NM_001135694.2.
DR RefSeq; NP_005653.3; NM_005662.6.
DR UniGene; Hs.699301; -.
DR ProteinModelPortal; Q9Y277; -.
DR SMR; Q9Y277; 5-283.
DR IntAct; Q9Y277; 8.
DR MINT; MINT-1395020; -.
DR STRING; 9606.ENSP00000388732; -.
DR DrugBank; DB01375; Dihydroxyaluminium.
DR PhosphoSite; Q9Y277; -.
DR DMDM; 12643945; -.
DR UCD-2DPAGE; Q9Y277; -.
DR PaxDb; Q9Y277; -.
DR PeptideAtlas; Q9Y277; -.
DR PRIDE; Q9Y277; -.
DR DNASU; 7419; -.
DR Ensembl; ENST00000022615; ENSP00000022615; ENSG00000078668.
DR Ensembl; ENST00000521158; ENSP00000428845; ENSG00000078668.
DR GeneID; 7419; -.
DR KEGG; hsa:7419; -.
DR UCSC; uc003xpc.3; human.
DR CTD; 7419; -.
DR GeneCards; GC08P042266; -.
DR HGNC; HGNC:12674; VDAC3.
DR HPA; HPA026864; -.
DR MIM; 610029; gene.
DR neXtProt; NX_Q9Y277; -.
DR PharmGKB; PA37297; -.
DR eggNOG; NOG243169; -.
DR HOGENOM; HOG000188277; -.
DR HOVERGEN; HBG054036; -.
DR InParanoid; Q9Y277; -.
DR KO; K15041; -.
DR PhylomeDB; Q9Y277; -.
DR ChiTaRS; VDAC3; human.
DR GeneWiki; VDAC3; -.
DR GenomeRNAi; 7419; -.
DR NextBio; 29048; -.
DR PRO; PR:Q9Y277; -.
DR ArrayExpress; Q9Y277; -.
DR Bgee; Q9Y277; -.
DR CleanEx; HS_VDAC3; -.
DR Genevestigator; Q9Y277; -.
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:0015853; P:adenine transport; TAS:ProtInc.
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; Ion transport;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; NAD;
KW Nucleotide-binding; Phosphoprotein; Porin; Reference proteome;
KW Transmembrane; Transmembrane beta strand; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 283 Voltage-dependent anion-selective channel
FT protein 3.
FT /FTId=PRO_0000050512.
FT TRANSMEM 26 35 Beta stranded; (By similarity).
FT TRANSMEM 39 47 Beta stranded; (By similarity).
FT TRANSMEM 54 64 Beta stranded; (By similarity).
FT TRANSMEM 69 76 Beta stranded; (By similarity).
FT TRANSMEM 80 89 Beta stranded; (By similarity).
FT TRANSMEM 95 104 Beta stranded; (By similarity).
FT TRANSMEM 111 120 Beta stranded; (By similarity).
FT TRANSMEM 123 130 Beta stranded; (By similarity).
FT TRANSMEM 137 145 Beta stranded; (By similarity).
FT TRANSMEM 150 158 Beta stranded; (By similarity).
FT TRANSMEM 163 175 Beta stranded; (By similarity).
FT TRANSMEM 178 185 Beta stranded; (By similarity).
FT TRANSMEM 189 198 Beta stranded; (By similarity).
FT TRANSMEM 202 211 Beta stranded; (By similarity).
FT TRANSMEM 218 227 Beta stranded; (By similarity).
FT TRANSMEM 231 238 Beta stranded; (By similarity).
FT TRANSMEM 242 251 Beta stranded; (By similarity).
FT TRANSMEM 254 263 Beta stranded; (By similarity).
FT TRANSMEM 273 282 Beta stranded; (By similarity).
FT NP_BIND 242 244 NAD (By similarity).
FT NP_BIND 260 264 NAD (By similarity).
FT MOD_RES 2 2 N-acetylcysteine.
FT MOD_RES 20 20 N6-acetyllysine.
FT MOD_RES 90 90 N6-acetyllysine.
FT MOD_RES 241 241 Phosphoserine (By similarity).
FT VAR_SEQ 39 39 V -> VM (in isoform 2).
FT /FTId=VSP_005079.
SQ SEQUENCE 283 AA; 30659 MW; E03CBCEDA72A9783 CRC64;
MCNTPTYCDL GKAAKDVFNK GYGFGMVKID LKTKSCSGVE FSTSGHAYTD TGKASGNLET
KYKVCNYGLT FTQKWNTDNT LGTEISWENK LAEGLKLTLD TIFVPNTGKK SGKLKASYKR
DCFSVGSNVD IDFSGPTIYG WAVLAFEGWL AGYQMSFDTA KSKLSQNNFA LGYKAADFQL
HTHVNDGTEF GGSIYQKVNE KIETSINLAW TAGSNNTRFG IAAKYMLDCR TSLSAKVNNA
SLIGLGYTQT LRPGVKLTLS ALIDGKNFSA GGHKVGLGFE LEA
//
ID VDAC3_HUMAN Reviewed; 283 AA.
AC Q9Y277; Q9UIS0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 119.
DE RecName: Full=Voltage-dependent anion-selective channel protein 3;
DE Short=VDAC-3;
DE Short=hVDAC3;
DE AltName: Full=Outer mitochondrial membrane protein porin 3;
GN Name=VDAC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9781040; DOI=10.1038/sj.ejhg.5200198;
RA Rahmani Z., Maunoury C., Siddiqui A.;
RT "Isolation of a novel human voltage-dependent anion channel gene.";
RL Eur. J. Hum. Genet. 6:337-340(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-
RT length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-253.
RX PubMed=10501981; DOI=10.1007/s003359901158;
RA Decker W.K., Bowles K.R., Schatte E.C., Towbin J.A., Craigen W.J.;
RT "Revised fine mapping of the human voltage-dependent anion channel
RT loci by radiation hybrid analysis.";
RL Mamm. Genome 10:1041-1042(1999).
RN [5]
RP ALTERNATIVE SPLICING.
RX PubMed=10833333; DOI=10.1006/mgme.2000.2987;
RA Decker W.K., Craigen W.J.;
RT "The tissue-specific, alternatively spliced single ATG exon of the
RT type 3 voltage-dependent anion channel gene does not create a
RT truncated protein isoform in vivo.";
RL Mol. Genet. Metab. 70:69-74(2000).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT CYS-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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-20 AND LYS-90, 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
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).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane
CC that allows diffusion of small hydrophilic molecules (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y277-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y277-2; Sequence=VSP_005079;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest in testis.
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 -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U90943; AAB93872.1; -; mRNA.
DR EMBL; AF038962; AAC39876.1; -; mRNA.
DR EMBL; BC056870; AAH56870.1; -; mRNA.
DR EMBL; AH008073; AAD49610.1; -; Genomic_DNA.
DR RefSeq; NP_001129166.1; NM_001135694.2.
DR RefSeq; NP_005653.3; NM_005662.6.
DR UniGene; Hs.699301; -.
DR ProteinModelPortal; Q9Y277; -.
DR SMR; Q9Y277; 5-283.
DR IntAct; Q9Y277; 8.
DR MINT; MINT-1395020; -.
DR STRING; 9606.ENSP00000388732; -.
DR DrugBank; DB01375; Dihydroxyaluminium.
DR PhosphoSite; Q9Y277; -.
DR DMDM; 12643945; -.
DR UCD-2DPAGE; Q9Y277; -.
DR PaxDb; Q9Y277; -.
DR PeptideAtlas; Q9Y277; -.
DR PRIDE; Q9Y277; -.
DR DNASU; 7419; -.
DR Ensembl; ENST00000022615; ENSP00000022615; ENSG00000078668.
DR Ensembl; ENST00000521158; ENSP00000428845; ENSG00000078668.
DR GeneID; 7419; -.
DR KEGG; hsa:7419; -.
DR UCSC; uc003xpc.3; human.
DR CTD; 7419; -.
DR GeneCards; GC08P042266; -.
DR HGNC; HGNC:12674; VDAC3.
DR HPA; HPA026864; -.
DR MIM; 610029; gene.
DR neXtProt; NX_Q9Y277; -.
DR PharmGKB; PA37297; -.
DR eggNOG; NOG243169; -.
DR HOGENOM; HOG000188277; -.
DR HOVERGEN; HBG054036; -.
DR InParanoid; Q9Y277; -.
DR KO; K15041; -.
DR PhylomeDB; Q9Y277; -.
DR ChiTaRS; VDAC3; human.
DR GeneWiki; VDAC3; -.
DR GenomeRNAi; 7419; -.
DR NextBio; 29048; -.
DR PRO; PR:Q9Y277; -.
DR ArrayExpress; Q9Y277; -.
DR Bgee; Q9Y277; -.
DR CleanEx; HS_VDAC3; -.
DR Genevestigator; Q9Y277; -.
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:0015853; P:adenine transport; TAS:ProtInc.
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; Ion transport;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; NAD;
KW Nucleotide-binding; Phosphoprotein; Porin; Reference proteome;
KW Transmembrane; Transmembrane beta strand; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 283 Voltage-dependent anion-selective channel
FT protein 3.
FT /FTId=PRO_0000050512.
FT TRANSMEM 26 35 Beta stranded; (By similarity).
FT TRANSMEM 39 47 Beta stranded; (By similarity).
FT TRANSMEM 54 64 Beta stranded; (By similarity).
FT TRANSMEM 69 76 Beta stranded; (By similarity).
FT TRANSMEM 80 89 Beta stranded; (By similarity).
FT TRANSMEM 95 104 Beta stranded; (By similarity).
FT TRANSMEM 111 120 Beta stranded; (By similarity).
FT TRANSMEM 123 130 Beta stranded; (By similarity).
FT TRANSMEM 137 145 Beta stranded; (By similarity).
FT TRANSMEM 150 158 Beta stranded; (By similarity).
FT TRANSMEM 163 175 Beta stranded; (By similarity).
FT TRANSMEM 178 185 Beta stranded; (By similarity).
FT TRANSMEM 189 198 Beta stranded; (By similarity).
FT TRANSMEM 202 211 Beta stranded; (By similarity).
FT TRANSMEM 218 227 Beta stranded; (By similarity).
FT TRANSMEM 231 238 Beta stranded; (By similarity).
FT TRANSMEM 242 251 Beta stranded; (By similarity).
FT TRANSMEM 254 263 Beta stranded; (By similarity).
FT TRANSMEM 273 282 Beta stranded; (By similarity).
FT NP_BIND 242 244 NAD (By similarity).
FT NP_BIND 260 264 NAD (By similarity).
FT MOD_RES 2 2 N-acetylcysteine.
FT MOD_RES 20 20 N6-acetyllysine.
FT MOD_RES 90 90 N6-acetyllysine.
FT MOD_RES 241 241 Phosphoserine (By similarity).
FT VAR_SEQ 39 39 V -> VM (in isoform 2).
FT /FTId=VSP_005079.
SQ SEQUENCE 283 AA; 30659 MW; E03CBCEDA72A9783 CRC64;
MCNTPTYCDL GKAAKDVFNK GYGFGMVKID LKTKSCSGVE FSTSGHAYTD TGKASGNLET
KYKVCNYGLT FTQKWNTDNT LGTEISWENK LAEGLKLTLD TIFVPNTGKK SGKLKASYKR
DCFSVGSNVD IDFSGPTIYG WAVLAFEGWL AGYQMSFDTA KSKLSQNNFA LGYKAADFQL
HTHVNDGTEF GGSIYQKVNE KIETSINLAW TAGSNNTRFG IAAKYMLDCR TSLSAKVNNA
SLIGLGYTQT LRPGVKLTLS ALIDGKNFSA GGHKVGLGFE LEA
//
MIM
610029
*RECORD*
*FIELD* NO
610029
*FIELD* TI
*610029 VOLTAGE-DEPENDENT ANION CHANNEL 3; VDAC3
*FIELD* TX
DESCRIPTION
VDAC3 belongs to a group of mitochondrial membrane channels involved in
read moretranslocation of adenine nucleotides through the outer membrane. These
channels may also function as a mitochondrial binding site for
hexokinase (see HK1; 142600) and glycerol kinase (GK; 300474) (Rahmani
et al., 1998).
CLONING
By PCR of a human liver cDNA library, Rahmani et al. (1998) cloned
VDAC3. The deduced 283-amino acid protein is 67% identical to VDAC1
(604492) and 73% identical to VDAC2 (193245). Northern blot analysis
detected a 1.4-kb transcript in all tissues examined, with high
expression in testis. SDS-PAGE of transfected COS-1 cells showed
epitope-tagged VDAC3 at about 30 kD.
GENE FUNCTION
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 (193245) or VDAC3 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
Using FISH, Rahmani et al. (1998) mapped the VDAC3 gene to chromosome
8p11.2. They stated that the mouse Vdac3 gene maps to a proximal region
of chromosome 8 that shares homology of synteny with human chromosome
8p.
ANIMAL MODEL
Sampson et al. (2001) found that Vdac3-null mice were born at the
expected mendelian ratio. Mutant females were fertile, but males were
not due to markedly reduced sperm motility. The majority of epididymal
axonemes showed structural defects, most commonly loss of a single
microtubule doublet at a conserved position within the axoneme. In
testicular sperm, the defect was only rarely observed, suggesting that
instability of a normally formed axoneme occurred during sperm
maturation. In contrast, tracheal epithelial cilia showed no structural
abnormalities, but there was a reduced number of ciliated cells. In
skeletal muscle, mitochondria were abnormally shaped, and the activities
of respiratory chain complex enzymes were reduced. Citrate synthase (CS;
118950) activity was unchanged, suggesting an absence of mitochondrial
proliferation that commonly occurs in response to respiratory chain
defects.
Anflous-Pharayra et al. (2007) found that Vdac3 -/- mice were
indistinguishable from wildtype. Soleus muscle from Vdac3 -/- mice
showed normal hexokinase-2 (HK2; 601125) protein content and activity
and normal glucose and exercise tolerance. Knockout of both Vdac3 and
Vdac1 resulted in partial lethality in utero, and live-born mice showed
a growth defect more pronounced than that of Vdac1 -/- mice.
Double-knockout mice also showed reduced glucose tolerance, similar to
Vdac1 -/- mice.
*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. Rahmani, Z.; Maunoury, C.; Siddiqui, A.: Isolation of a novel
human voltage-dependent anion channel gene. Europ. J. Hum. Genet. 6:
334-340, 1998.
3. Sampson, M. J.; Decker, W. K.; Beaudet, A. L.; Ruitenbeek, W.;
Armstrong, D.; Hicks, M. J.; Craigen, W. J.: Immotile sperm and infertility
in mice lacking mitochondrial voltage-dependent anion channel type
3. J. Biol. Chem. 276: 39206-39212, 2001.
4. 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
Patricia A. Hartz - updated: 2/21/2012
Ada Hamosh - updated: 6/29/2007
*FIELD* CD
Patricia A. Hartz: 4/7/2006
*FIELD* ED
mgross: 03/06/2012
terry: 2/21/2012
alopez: 7/3/2007
terry: 6/29/2007
mgross: 4/7/2006
*RECORD*
*FIELD* NO
610029
*FIELD* TI
*610029 VOLTAGE-DEPENDENT ANION CHANNEL 3; VDAC3
*FIELD* TX
DESCRIPTION
VDAC3 belongs to a group of mitochondrial membrane channels involved in
read moretranslocation of adenine nucleotides through the outer membrane. These
channels may also function as a mitochondrial binding site for
hexokinase (see HK1; 142600) and glycerol kinase (GK; 300474) (Rahmani
et al., 1998).
CLONING
By PCR of a human liver cDNA library, Rahmani et al. (1998) cloned
VDAC3. The deduced 283-amino acid protein is 67% identical to VDAC1
(604492) and 73% identical to VDAC2 (193245). Northern blot analysis
detected a 1.4-kb transcript in all tissues examined, with high
expression in testis. SDS-PAGE of transfected COS-1 cells showed
epitope-tagged VDAC3 at about 30 kD.
GENE FUNCTION
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 (193245) or VDAC3 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
Using FISH, Rahmani et al. (1998) mapped the VDAC3 gene to chromosome
8p11.2. They stated that the mouse Vdac3 gene maps to a proximal region
of chromosome 8 that shares homology of synteny with human chromosome
8p.
ANIMAL MODEL
Sampson et al. (2001) found that Vdac3-null mice were born at the
expected mendelian ratio. Mutant females were fertile, but males were
not due to markedly reduced sperm motility. The majority of epididymal
axonemes showed structural defects, most commonly loss of a single
microtubule doublet at a conserved position within the axoneme. In
testicular sperm, the defect was only rarely observed, suggesting that
instability of a normally formed axoneme occurred during sperm
maturation. In contrast, tracheal epithelial cilia showed no structural
abnormalities, but there was a reduced number of ciliated cells. In
skeletal muscle, mitochondria were abnormally shaped, and the activities
of respiratory chain complex enzymes were reduced. Citrate synthase (CS;
118950) activity was unchanged, suggesting an absence of mitochondrial
proliferation that commonly occurs in response to respiratory chain
defects.
Anflous-Pharayra et al. (2007) found that Vdac3 -/- mice were
indistinguishable from wildtype. Soleus muscle from Vdac3 -/- mice
showed normal hexokinase-2 (HK2; 601125) protein content and activity
and normal glucose and exercise tolerance. Knockout of both Vdac3 and
Vdac1 resulted in partial lethality in utero, and live-born mice showed
a growth defect more pronounced than that of Vdac1 -/- mice.
Double-knockout mice also showed reduced glucose tolerance, similar to
Vdac1 -/- mice.
*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. Rahmani, Z.; Maunoury, C.; Siddiqui, A.: Isolation of a novel
human voltage-dependent anion channel gene. Europ. J. Hum. Genet. 6:
334-340, 1998.
3. Sampson, M. J.; Decker, W. K.; Beaudet, A. L.; Ruitenbeek, W.;
Armstrong, D.; Hicks, M. J.; Craigen, W. J.: Immotile sperm and infertility
in mice lacking mitochondrial voltage-dependent anion channel type
3. J. Biol. Chem. 276: 39206-39212, 2001.
4. 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
Patricia A. Hartz - updated: 2/21/2012
Ada Hamosh - updated: 6/29/2007
*FIELD* CD
Patricia A. Hartz: 4/7/2006
*FIELD* ED
mgross: 03/06/2012
terry: 2/21/2012
alopez: 7/3/2007
terry: 6/29/2007
mgross: 4/7/2006