VDAC1_RABIT
ID VDAC1_RABIT Reviewed; 283 AA.
AC Q9TT15;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Voltage-dependent anion-selective channel protein 1;
DE Short=VDAC-1;
DE AltName: Full=Outer mitochondrial membrane protein porin 1;
GN Name=VDAC1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Corneal endothelium;
RA Rae J.L.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Forms a channel through the mitochondrial outer membrane and
CC also the plasma membrane. The channel at the outer mitochondrial
CC membrane allows diffusion of small hydrophilic molecules; in the plasma
CC membrane it is involved in cell volume regulation and apoptosis. It
CC adopts an open conformation at low or zero membrane potential and a
CC closed conformation at potentials above 30-40 mV. The open state has a
CC weak anion selectivity whereas the closed state is cation-selective.
CC Binds various signaling molecules, including the sphingolipid ceramide,
CC the phospholipid phosphatidylcholine, and the sterol cholesterol. In
CC depolarized mitochondria, acts downstream of PRKN and PINK1 to promote
CC mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes
CC mitophagy, while monoubiquitination by PRKN decreases mitochondrial
CC calcium influx which ultimately inhibits apoptosis. May participate in
CC the formation of the permeability transition pore complex (PTPC)
CC responsible for the release of mitochondrial products that triggers
CC apoptosis. May mediate ATP export from cells.
CC {ECO:0000250|UniProtKB:P21796}.
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 -!- 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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF209725; AAF22835.1; -; mRNA.
DR RefSeq; NP_001075544.1; NM_001082075.1.
DR RefSeq; XP_008253053.1; XM_008254831.2.
DR AlphaFoldDB; Q9TT15; -.
DR BMRB; Q9TT15; -.
DR SMR; Q9TT15; -.
DR STRING; 9986.ENSOCUP00000008083; -.
DR PRIDE; Q9TT15; -.
DR Ensembl; ENSOCUT00000009371; ENSOCUP00000008083; ENSOCUG00000009369.
DR GeneID; 100008751; -.
DR KEGG; ocu:100008751; -.
DR CTD; 7416; -.
DR eggNOG; KOG3126; Eukaryota.
DR GeneTree; ENSGT00950000182869; -.
DR HOGENOM; CLU_044399_2_0_1; -.
DR InParanoid; Q9TT15; -.
DR OMA; IKTAYKC; -.
DR OrthoDB; 938262at2759; -.
DR TreeFam; TF315091; -.
DR Proteomes; UP000001811; Chromosome 3.
DR Bgee; ENSOCUG00000009369; Expressed in skeletal muscle tissue and 15 other tissues.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; 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; ISS:UniProtKB.
DR GO; GO:0006820; P:anion transport; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Apoptosis; Cell membrane; Ion transport; Isopeptide bond;
KW Lipid-binding; Membrane; Mitochondrion; Mitochondrion outer membrane; NAD;
KW Nucleotide-binding; Phosphoprotein; Porin; Reference proteome;
KW Transmembrane; Transmembrane beta strand; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P21796"
FT CHAIN 2..283
FT /note="Voltage-dependent anion-selective channel protein 1"
FT /id="PRO_0000050502"
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:0000250|UniProtKB:P21796"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2L0"
FT MOD_RES 19
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60932"
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 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"
SQ SEQUENCE 283 AA; 30741 MW; 9CAE6D8D50A18BD5 CRC64;
MAVPPTYADL GKSARDVFTK GYGFGLIKLD LKTKSENGLE FTSSGSANTE TTKVTGSLET
KYRWTEYGLT FTEKWNTDNT LGTEITVEDQ LARGLKLTFD SSFSPNTGKK NAKIKTGYKR
EHINLGCDVD FDIAGPSIRG ALVLGYEGWL AGYQMNFETA KSRVTQSNFA VGYKTDEFQL
HTNVNDGTEF GGSIYQKVNK KLETAVNLAW TAGNSNTRFG IAAKYQIDPD ACFSAKVNNS
SLIGLGYTQT LKPGIKLTLS ALLDGKNVNA GGHKLGLGLE FQA
