ADT1_RAT
ID ADT1_RAT Reviewed; 298 AA.
AC Q05962;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=ADP/ATP translocase 1 {ECO:0000305};
DE AltName: Full=ADP,ATP carrier protein 1 {ECO:0000250|UniProtKB:P48962};
DE AltName: Full=Adenine nucleotide translocator 1 {ECO:0000303|PubMed:8399300};
DE Short=ANT 1 {ECO:0000303|PubMed:8399300};
DE AltName: Full=Solute carrier family 25 member 4 {ECO:0000305};
GN Name=Slc25a4 {ECO:0000312|RGD:620352};
GN Synonyms=Aac1 {ECO:0000250|UniProtKB:P48962},
GN Ant1 {ECO:0000303|PubMed:8399300};
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 [GENOMIC DNA / MRNA].
RC STRAIN=Sprague-Dawley, and Wistar; TISSUE=Heart, and Liver;
RX PubMed=8399300; DOI=10.1016/0005-2736(93)90248-x;
RA Shinohara Y., Kamida M., Yamazaki N., Terada H.;
RT "Isolation and characterization of cDNA clones and a genomic clone encoding
RT rat mitochondrial adenine nucleotide translocator.";
RL Biochim. Biophys. Acta 1152:192-196(1993).
RN [2]
RP PROTEIN SEQUENCE OF 2-31; 34-43; 73-80 AND 273-280, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT GLY-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Pheochromocytoma;
RA Bienvenut W.V., von Kriegsheim A.F., Kolch W.;
RL Submitted (AUG-2006) to UniProtKB.
RN [3]
RP S-NITROSYLATION [LARGE SCALE ANALYSIS] AT CYS-160, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16418269; DOI=10.1073/pnas.0508412103;
RA Hao G., Derakhshan B., Shi L., Campagne F., Gross S.S.;
RT "SNOSID, a proteomic method for identification of cysteine S-nitrosylation
RT sites in complex protein mixtures.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:1012-1017(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-149 AND SER-150, AND
RP IDENTIFICATION BY 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 [5]
RP METHYLATION AT LYS-52.
RX PubMed=31213526; DOI=10.1074/jbc.ra119.009045;
RA Malecki J., Willemen H.L.D.M., Pinto R., Ho A.Y.Y., Moen A., Eijkelkamp N.,
RA Falnes P.O.;
RT "Human FAM173A is a mitochondrial lysine-specific methyltransferase that
RT targets adenine nucleotide translocase and affects mitochondrial
RT respiration.";
RL J. Biol. Chem. 294:11654-11664(2019).
CC -!- FUNCTION: ADP:ATP antiporter that mediates import of ADP into the
CC mitochondrial matrix for ATP synthesis, and export of ATP out to fuel
CC the cell (By similarity). Cycles between the cytoplasmic-open state (c-
CC state) and the matrix-open state (m-state): operates by the alternating
CC access mechanism with a single substrate-binding site intermittently
CC exposed to either the cytosolic (c-state) or matrix (m-state) side of
CC the inner mitochondrial membrane (By similarity). In addition to its
CC ADP:ATP antiporter activity, also involved in mitochondrial uncoupling
CC and mitochondrial permeability transition pore (mPTP) activity (By
CC similarity). Plays a role in mitochondrial uncoupling by acting as a
CC proton transporter: proton transport uncouples the proton flows via the
CC electron transport chain and ATP synthase to reduce the efficiency of
CC ATP production and cause mitochondrial thermogenesis. Proton
CC transporter activity is inhibited by ADP:ATP antiporter activity,
CC suggesting that SLC25A4/ANT1 acts as a master regulator of
CC mitochondrial energy output by maintaining a delicate balance between
CC ATP production (ADP:ATP antiporter activity) and thermogenesis (proton
CC transporter activity). Proton transporter activity requires free fatty
CC acids as cofactor, but does not transport it (By similarity). Also
CC plays a key role in mPTP opening, a non-specific pore that enables free
CC passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and
CC which contributes to cell death (By similarity). It is however unclear
CC if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or
CC regulates it (By similarity). Acts as a regulator of mitophagy
CC independently of ADP:ATP antiporter activity: promotes mitophagy via
CC interaction with TIMM44, leading to inhibit the presequence translocase
CC TIMM23, thereby promoting stabilization of PINK1 (By similarity).
CC {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P12235,
CC ECO:0000250|UniProtKB:P48962}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP(in) + ATP(out) = ADP(out) + ATP(in); Xref=Rhea:RHEA:34999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P12235};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000250|UniProtKB:P48962};
CC -!- ACTIVITY REGULATION: The matrix-open state (m-state) is inhibited by
CC the membrane-permeable bongkrekic acid (BKA) (By similarity). The
CC cytoplasmic-open state (c-state) is inhibited by the membrane-
CC impermeable toxic inhibitor carboxyatractyloside (CATR) (By
CC similarity). Proton transporter activity is inhibited by ADP:ATP
CC antiporter activity (By similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P12235, ECO:0000250|UniProtKB:P48962}.
CC -!- SUBUNIT: Monomer (By similarity). Found in a complex with ARL2, ARL2BP
CC and SLC25A4/ANT1. Interacts with ARL2BP. Interacts with TIMM44; leading
CC to inhibit the presequence translocase TIMM23, thereby promoting
CC stabilization of PINK1 (By similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P02722, ECO:0000250|UniProtKB:P48962}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P12235}; Multi-pass membrane protein
CC {ECO:0000255}. Membrane {ECO:0000250|UniProtKB:P12235}; Multi-pass
CC membrane protein {ECO:0000255}. Note=The complex formed with ARL2BP,
CC ARL2 and SLC25A4/ANT1 is expressed in mitochondria (By similarity). May
CC localize to non-mitochondrial membranes (By similarity).
CC {ECO:0000250|UniProtKB:P12235, ECO:0000250|UniProtKB:P48962}.
CC -!- DOMAIN: The transmembrane helices are not perpendicular to the plane of
CC the membrane, but cross the membrane at an angle. Odd-numbered
CC transmembrane helices exhibit a sharp kink, due to the presence of a
CC conserved proline residue. {ECO:0000250|UniProtKB:P02722}.
CC -!- PTM: Under cell death induction, transglutaminated by TGM2.
CC Transglutamination leads to formation of covalent cross-links between a
CC glutamine and the epsilon-amino group of a lysine residue, forming
CC polymers. {ECO:0000250|UniProtKB:P48962}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; X61667; CAA43842.1; -; Genomic_DNA.
DR EMBL; D12770; BAA02237.1; -; mRNA.
DR PIR; I60173; I60173.
DR RefSeq; NP_445967.1; NM_053515.1.
DR AlphaFoldDB; Q05962; -.
DR SMR; Q05962; -.
DR BioGRID; 250085; 7.
DR CORUM; Q05962; -.
DR IntAct; Q05962; 7.
DR MINT; Q05962; -.
DR STRING; 10116.ENSRNOP00000014704; -.
DR CarbonylDB; Q05962; -.
DR iPTMnet; Q05962; -.
DR PhosphoSitePlus; Q05962; -.
DR jPOST; Q05962; -.
DR PaxDb; Q05962; -.
DR PRIDE; Q05962; -.
DR GeneID; 85333; -.
DR KEGG; rno:85333; -.
DR CTD; 291; -.
DR RGD; 620352; Slc25a4.
DR eggNOG; KOG0749; Eukaryota.
DR InParanoid; Q05962; -.
DR OrthoDB; 870903at2759; -.
DR PhylomeDB; Q05962; -.
DR Reactome; R-RNO-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR PRO; PR:Q05962; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:CAFA.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:MGI.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005471; F:ATP:ADP antiporter activity; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; ISS:UniProtKB.
DR GO; GO:0015078; F:proton transmembrane transporter activity; ISO:RGD.
DR GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB.
DR GO; GO:0015866; P:ADP transport; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:RGD.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0140021; P:mitochondrial ADP transmembrane transport; ISS:UniProtKB.
DR GO; GO:1990544; P:mitochondrial ATP transmembrane transport; ISS:UniProtKB.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IDA:RGD.
DR GO; GO:1902109; P:negative regulation of mitochondrial membrane permeability involved in apoptotic process; IDA:RGD.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISO:RGD.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IDA:RGD.
DR GO; GO:1901526; P:positive regulation of mitophagy; ISS:UniProtKB.
DR GO; GO:2000277; P:positive regulation of oxidative phosphorylation uncoupler activity; IMP:RGD.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISO:RGD.
DR GO; GO:0070555; P:response to interleukin-1; IEP:RGD.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002113; ADT_euk_type.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR PANTHER; PTHR45635; PTHR45635; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00927; ADPTRNSLCASE.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Acetylation; Antiport; Direct protein sequencing; Membrane; Methylation;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Repeat; S-nitrosylation; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.2"
FT CHAIN 2..298
FT /note="ADP/ATP translocase 1"
FT /id="PRO_0000090577"
FT TOPO_DOM 1..7
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 8..37
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 38..74
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 75..99
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 100..109
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 110..130
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 131..178
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 179..199
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 200..210
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 211..231
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 232..273
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 274..291
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 292..298
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT REPEAT 6..98
FT /note="Solcar 1"
FT REPEAT 111..201
FT /note="Solcar 2"
FT REPEAT 212..297
FT /note="Solcar 3"
FT REGION 235..240
FT /note="Important for transport activity"
FT /evidence="ECO:0000250|UniProtKB:P12235"
FT MOTIF 235..240
FT /note="Nucleotide carrier signature motif"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 80
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 92
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 235
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0000269|Ref.2"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 52
FT /note="N6,N6,N6-trimethyllysine"
FT /evidence="ECO:0000269|PubMed:31213526"
FT MOD_RES 147
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48962"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 160
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0007744|PubMed:16418269"
FT MOD_RES 245
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48962"
FT MOD_RES 272
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48962"
SQ SEQUENCE 298 AA; 32989 MW; 66704FF78C6BC320 CRC64;
MGDQALSFLK DFLAGGIAAA VSKTAVAPIE RVKLLLQVQH ASKQISAEKQ YKGIIDCVVR
IPKEQGFLSF WRGNLANVIR YFPTQALNFA FKDKYKQIFL GGVDRHKQFW RYFAGNLASG
GAAGATSLCF VYPLDFARTR LAADVGKGSS QREFNGLGDC LTKIFKSDGL KGLYQGFSVS
VQGIIIYRAA YFGVYDTAKG MLPDPKNVHI IVSWMIAQSV TAVAGLVSYP FDTVRRRMMM
QSGRKGADIM YTGTVDCWRK IAKDEGRKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYV
