VDAC1_RAT
ID VDAC1_RAT Reviewed; 283 AA.
AC Q9Z2L0; A1L125; Q3MHT8; Q5M944; Q5M972; Q6IN28; Q6P9W9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Voltage-dependent anion-selective channel protein 1;
DE Short=VDAC-1;
DE Short=rVDAC1;
DE AltName: Full=Outer mitochondrial membrane protein porin 1;
GN Name=Vdac1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=9714728; DOI=10.1016/s0167-4781(98)00088-8;
RA Anflous K., Blondel O., Bernard A., Khrestchatisky M., Ventura-Clapier R.;
RT "Characterization of rat porin isoforms: cloning of a cardiac type-3
RT variant encoding an additional methionine at its putative N-terminal
RT region.";
RL Biochim. Biophys. Acta 1399:47-50(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Ascitic tumor;
RX PubMed=10998068; DOI=10.1046/j.1432-1327.2000.01687.x;
RA Shinohara Y., Ishida T., Hino M., Yamazaki N., Baba Y., Terada H.;
RT "Characterization of porin isoforms expressed in tumor cells.";
RL Eur. J. Biochem. 267:6067-6073(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Lens;
RA Rae J.L.;
RT "Ion channels in the lens.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Embryonic brain, Heart, Ovary, Pituitary, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-14 AND 135-138, ACETYLATION AT ALA-2, PHOSPHORYLATION
RP AT SER-13 AND SER-137, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=17478130; DOI=10.1016/j.bbapap.2007.03.012;
RA Distler A.M., Kerner J., Hoppel C.L.;
RT "Post-translational modifications of rat liver mitochondrial outer membrane
RT proteins identified by mass spectrometry.";
RL Biochim. Biophys. Acta 1774:628-636(2007).
RN [6]
RP PROTEIN SEQUENCE OF 21-28; 33-53; 64-74; 75-93; 97-109; 121-139; 164-197;
RP 201-218 AND 225-266, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA Lubec G., Chen W.-Q., Afjehi-Sadat L., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF SER-137.
RX PubMed=25628567; DOI=10.3389/fphys.2014.00513;
RA Tewari S.G., Zhou Y., Otto B.J., Dash R.K., Kwok W.M., Beard D.A.;
RT "Markov chain Monte Carlo based analysis of post-translationally modified
RT VDAC gating kinetics.";
RL Front. Physiol. 5:513-513(2014).
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane and
CC also the plasma membrane (By similarity). The channel at the outer
CC mitochondrial membrane allows diffusion of small hydrophilic molecules;
CC in the plasma membrane it is involved in cell volume regulation and
CC apoptosis (By similarity). It adopts an open conformation at low or
CC zero membrane potential and a closed conformation at potentials above
CC 30-40 mV (By similarity). The open state has a weak anion selectivity
CC whereas the closed state is cation-selective (PubMed:25628567). Binds
CC various signaling molecules, including the sphingolipid ceramide, the
CC phospholipid phosphatidylcholine, and the sterol cholesterol (By
CC similarity). In depolarized mitochondria, acts downstream of PRKN and
CC PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by
CC PRKN promotes mitophagy, while monoubiquitination by PRKN decreases
CC mitochondrial calcium influx which ultimately inhibits apoptosis (By
CC similarity). May participate in the formation of the permeability
CC transition pore complex (PTPC) responsible for the release of
CC mitochondrial products that triggers apoptosis (By similarity). May
CC mediate ATP export from cells (By similarity).
CC {ECO:0000250|UniProtKB:P21796, ECO:0000269|PubMed:25628567}.
CC -!- ACTIVITY REGULATION: Inhibited by nitric oxide.
CC {ECO:0000250|UniProtKB:P21796}.
CC -!- SUBUNIT: Homodimer and homotrimer; in response to cyclic AMP or
CC calcium. Interacts with hexokinases including HK1. The HK1-VDAC1
CC complex interacts with ATF2. Interacts with BCL2L1. Interacts with
CC BAK1. Interacts with RTL10/BOP (via BH3 domain). Interacts with
CC amyloid-beta and APP; induces VDAC1 dephosphorylation. Component of the
CC mitochondrial permeability transition pore complex (mPTPC), at least
CC composed of SPG7, VDAC1 and PPIF. Interacts with SPG7, NIPSNAP2 and
CC SLC25A30. Interacts with TMEM41B. Interacts with BCAP31.
CC {ECO:0000250|UniProtKB:P21796}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P21796}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P21796}. Cell membrane
CC {ECO:0000250|UniProtKB:P21796}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P21796}. Membrane raft
CC {ECO:0000250|UniProtKB:P21796}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P21796}.
CC -!- TISSUE SPECIFICITY: Widely expressed. High levels in heart and kidney
CC with lower levels in brain and ascitic tumor. Very low levels in liver.
CC {ECO:0000269|PubMed:10998068}.
CC -!- DOMAIN: Consists mainly of a membrane-spanning beta-barrel formed by 19
CC beta-strands. The helical N-terminus folds back into the pore opening
CC and plays a role in voltage-gated channel activity.
CC {ECO:0000250|UniProtKB:P21796}.
CC -!- PTM: Phosphorylation at Ser-193 by NEK1 promotes the open
CC conformational state preventing excessive mitochondrial membrane
CC permeability and subsequent apoptotic cell death after injury.
CC Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably
CC by preventing ubiquitin-mediated proteasomal degradation.
CC {ECO:0000250|UniProtKB:P21796}.
CC -!- PTM: Ubiquitinated. Undergoes monoubiquitination and polyubiquitination
CC by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas
CC polyubiquitination leads to its degradation and promotes mitophagy.
CC Deubiquitinated by USP30. {ECO:0000250|UniProtKB:P21796}.
CC -!- SIMILARITY: Belongs to the eukaryotic mitochondrial porin family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH60558.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF048828; AAD02476.1; -; mRNA.
DR EMBL; AB039662; BAB13473.1; -; mRNA.
DR EMBL; AF268467; AAF80115.1; -; mRNA.
DR EMBL; BC060558; AAH60558.1; ALT_INIT; mRNA.
DR EMBL; BC072484; AAH72484.2; -; mRNA.
DR EMBL; BC087573; AAH87573.2; -; mRNA.
DR EMBL; BC087657; AAH87657.2; -; mRNA.
DR EMBL; BC104684; AAI04685.2; -; mRNA.
DR EMBL; BC127491; AAI27492.1; -; mRNA.
DR RefSeq; NP_112643.1; NM_031353.1.
DR AlphaFoldDB; Q9Z2L0; -.
DR SMR; Q9Z2L0; -.
DR BioGRID; 249746; 7.
DR CORUM; Q9Z2L0; -.
DR DIP; DIP-37068N; -.
DR IntAct; Q9Z2L0; 9.
DR MINT; Q9Z2L0; -.
DR STRING; 10116.ENSRNOP00000008477; -.
DR CarbonylDB; Q9Z2L0; -.
DR iPTMnet; Q9Z2L0; -.
DR PhosphoSitePlus; Q9Z2L0; -.
DR SwissPalm; Q9Z2L0; -.
DR World-2DPAGE; 0004:Q9Z2L0; -.
DR jPOST; Q9Z2L0; -.
DR PaxDb; Q9Z2L0; -.
DR PRIDE; Q9Z2L0; -.
DR ABCD; Q9Z2L0; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000008477; ENSRNOP00000008477; ENSRNOG00000006375.
DR GeneID; 83529; -.
DR KEGG; rno:83529; -.
DR UCSC; RGD:621575; rat.
DR CTD; 7416; -.
DR RGD; 621575; Vdac1.
DR eggNOG; KOG3126; Eukaryota.
DR GeneTree; ENSGT00950000182869; -.
DR HOGENOM; CLU_044399_2_0_1; -.
DR InParanoid; Q9Z2L0; -.
DR OMA; IKTAYKC; -.
DR OrthoDB; 938262at2759; -.
DR PhylomeDB; Q9Z2L0; -.
DR TreeFam; TF315091; -.
DR Reactome; R-RNO-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-70268; Pyruvate metabolism.
DR PRO; PR:Q9Z2L0; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000006375; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q9Z2L0; RN.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:RGD.
DR GO; GO:0042645; C:mitochondrial nucleoid; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:RGD.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0005253; F:anion channel activity; IDA:RGD.
DR GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
DR GO; GO:0097001; F:ceramide binding; ISO:RGD.
DR GO; GO:0015485; F:cholesterol binding; ISO:RGD.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0031210; F:phosphatidylcholine binding; ISO:RGD.
DR GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0008308; F:voltage-gated anion channel activity; IDA:RGD.
DR GO; GO:0006820; P:anion transport; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0007612; P:learning; ISO:RGD.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0110099; P:negative regulation of calcium import into the mitochondrion; ISO:RGD.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0007270; P:neuron-neuron synaptic transmission; ISO:RGD.
DR GO; GO:1901526; P:positive regulation of mitophagy; ISO:RGD.
DR GO; GO:1905091; P:positive regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; ISO:RGD.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; ISO:RGD.
DR CDD; cd07306; Porin3_VDAC; 1.
DR Gene3D; 2.40.160.10; -; 1.
DR InterPro; IPR023614; Porin_dom_sf.
DR InterPro; IPR001925; Porin_Euk.
DR InterPro; IPR027246; Porin_Euk/Tom40.
DR InterPro; IPR030270; VDAC1.
DR PANTHER; PTHR11743; PTHR11743; 1.
DR PANTHER; PTHR11743:SF13; PTHR11743:SF13; 1.
DR Pfam; PF01459; Porin_3; 1.
DR PRINTS; PR00185; EUKARYTPORIN.
DR PROSITE; PS00558; EUKARYOTIC_PORIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; Cell membrane; Direct protein sequencing;
KW Ion transport; Isopeptide bond; Lipid-binding; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; NAD; Nucleotide-binding; Phosphoprotein;
KW Porin; Reference proteome; Transmembrane; Transmembrane beta strand;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CHAIN 2..283
FT /note="Voltage-dependent anion-selective channel protein 1"
FT /id="PRO_0000050503"
FT TRANSMEM 26..35
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 39..47
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 54..64
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 69..76
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 80..89
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 95..104
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 111..120
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 123..130
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 137..145
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 150..158
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 163..175
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 178..185
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 189..198
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 202..211
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 218..227
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 231..238
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 242..251
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 254..263
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT TRANSMEM 273..282
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT BINDING 242..244
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT BINDING 260..264
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT SITE 73
FT /note="Involved in ceramide and phosphatidylcholine
FT binding. Critical for channel structural stability and
FT gating"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:17478130"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17478130"
FT MOD_RES 19
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 20
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT MOD_RES 20
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60932"
FT MOD_RES 67
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q60932"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT MOD_RES 109
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60932"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17478130"
FT MOD_RES 193
FT /note="Phosphoserine; by NEK1"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q60932"
FT MOD_RES 266
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 12
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 20
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P45880"
FT CROSSLNK 53
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 61
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 109
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 110
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 161
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 266
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CROSSLNK 274
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT MUTAGEN 137
FT /note="S->E: Channel conformation is shifted toward the
FT open state."
FT /evidence="ECO:0000269|PubMed:25628567"
FT CONFLICT 55
FT /note="N -> T (in Ref. 1; AAD02476)"
FT /evidence="ECO:0000305"
FT CONFLICT 83
FT /note="T -> S (in Ref. 1; AAD02476)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="V -> M (in Ref. 1; AAD02476)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="G -> GFDIAGPSIRGALVLGYEG (in Ref. 1; AAD02476)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 283 AA; 30756 MW; D32B05B8A8D75732 CRC64;
MAVPPTYADL GKSARDVFTK GYGFGLIKLD LKTKSENGLE FTSSGSANTE TTKVNGSLET
KYRWTEYGLT FTEKWNTDNT LGTEITVEDQ LARGLKLTFD SSFSPNTGKK NAKIKTGYKR
EHINLGCDVD FDIAGPSIRG ALVLGYEGWL AGYQMNFETS KSRVTQSNFA VGYKTDEFQL
HTNVNDGTEF GGSIYQKVNK KLETAVNLAW TAGNSNTRFG IAAKYQVDPD ACFSAKVNNS
SLIGLGYTQT LKPGIKLTLS ALLDGKNVNA GGHKLGLGLE FQA
