ID   ADT1_BOVIN              Reviewed;         298 AA.
AC   P02722;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=ADP/ATP translocase 1 {ECO:0000303|PubMed:2540808};
DE   AltName: Full=ADP,ATP carrier protein 1 {ECO:0000303|PubMed:7076130};
DE   AltName: Full=ADP,ATP carrier protein, heart isoform T1 {ECO:0000303|PubMed:2540808};
DE   AltName: Full=Adenine nucleotide translocator 1 {ECO:0000303|PubMed:2540808};
DE            Short=ANT 1 {ECO:0000303|PubMed:2540808};
DE   AltName: Full=Solute carrier family 25 member 4 {ECO:0000305};
GN   Name=SLC25A4 {ECO:0000250|UniProtKB:P12235};
GN   Synonyms=AAC1 {ECO:0000250|UniProtKB:P48962}, ANT1
GN   {ECO:0000303|PubMed:2540808};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=2540808; DOI=10.1021/bi00428a069;
RA   Powell S.J., Medd S.M., Runswick M.J., Walker J.E.;
RT   "Two bovine genes for mitochondrial ADP/ATP translocase expressed
RT   differences in various tissues.";
RL   Biochemistry 28:866-873(1989).
RN   [2]
RP   PROTEIN SEQUENCE OF 2-298, AND ACETYLATION AT SER-2.
RX   PubMed=7076130;
RA   Aquila H., Misra D., Eulitz M., Klingenberg M.;
RT   "Complete amino acid sequence of the ADP/ATP carrier from beef heart
RT   mitochondria.";
RL   Hoppe-Seyler's Z. Physiol. Chem. 363:345-349(1982).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 208-298.
RX   PubMed=3017341; DOI=10.1016/s0006-291x(86)80574-5;
RA   Rasmussen U.B., Wohlrab H.;
RT   "Bovine cardiac mitochondrial ADP/ATP-carrier: two distinct mRNAs and an
RT   unusually short 3'-noncoding sequence.";
RL   Biochem. Biophys. Res. Commun. 138:850-857(1986).
RN   [4]
RP   FUNCTION.
RX   PubMed=7961643; DOI=10.1016/s0021-9258(18)46989-x;
RA   Brustovetsky N., Klingenberg M.;
RT   "The reconstituted ADP/ATP carrier can mediate H+ transport by free fatty
RT   acids, which is further stimulated by mersalyl.";
RL   J. Biol. Chem. 269:27329-27336(1994).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH INHIBITOR, TISSUE
RP   SPECIFICITY, SUBCELLULAR LOCATION, TOPOLOGY, AND DOMAIN.
RX   PubMed=14603310; DOI=10.1038/nature02056;
RA   Pebay-Peyroula E., Dahout-Gonzalez C., Kahn R., Trezeguet V.,
RA   Lauquin G.J.-M., Brandolin G.;
RT   "Structure of mitochondrial ADP/ATP carrier in complex with
RT   carboxyatractyloside.";
RL   Nature 426:39-44(2003).
RN   [6] {ECO:0007744|PDB:2C3E}
RP   X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2-298, TISSUE SPECIFICITY,
RP   SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, AND DOMAIN.
RX   PubMed=16226253; DOI=10.1016/j.febslet.2005.09.061;
RA   Nury H., Dahout-Gonzalez C., Trezeguet V., Lauquin G., Brandolin G.,
RA   Pebay-Peyroula E.;
RT   "Structural basis for lipid-mediated interactions between mitochondrial
RT   ADP/ATP carrier monomers.";
RL   FEBS Lett. 579:6031-6036(2005).
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 (PubMed:7961643).
CC       Proton transporter activity is inhibited by ADP:ATP antiporter
CC       activity, 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) (By similarity). Proton transporter activity
CC       requires free fatty acids as cofactor, but does not transport it
CC       (PubMed:7961643). Probably mediates mitochondrial uncoupling in tissues
CC       that do not express UCP1 (By similarity). Also plays a key role in mPTP
CC       opening, a non-specific pore that enables free passage of the
CC       mitochondrial membranes to solutes of up to 1.5 kDa, and which
CC       contributes to cell death (By similarity). It is however unclear if
CC       SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates
CC       it (By similarity). Acts as a regulator of mitophagy independently of
CC       ADP:ATP antiporter activity: promotes mitophagy via interaction with
CC       TIMM44, leading to inhibit the presequence translocase TIMM23, thereby
CC       promoting stabilization of PINK1 (By similarity).
CC       {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P48962,
CC       ECO:0000269|PubMed:7961643}.
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:P48962};
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). The cytoplasmic-open
CC       state (c-state) is inhibited by the membrane-impermeable toxic
CC       inhibitor carboxyatractyloside (CATR) (By similarity). Proton
CC       transporter activity is inhibited by ADP:ATP antiporter activity (By
CC       similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC       ECO:0000250|UniProtKB:P48962}.
CC   -!- SUBUNIT: Monomer (PubMed:16226253). Found in a complex with ARL2,
CC       ARL2BP and SLC25A4/ANT1. Interacts with ARL2BP. Interacts with TIMM44;
CC       leading to inhibit the presequence translocase TIMM23, thereby
CC       promoting stabilization of PINK1 (By similarity).
CC       {ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:16226253}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000305|PubMed:14603310, ECO:0000305|PubMed:16226253}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:14603310,
CC       ECO:0000269|PubMed:16226253}. Membrane {ECO:0000250|UniProtKB:P12235};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:14603310,
CC       ECO:0000269|PubMed:16226253}. Note=The complex formed with ARL2BP, ARL2
CC       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   -!- TISSUE SPECIFICITY: Detected in heart muscle (at protein level)
CC       (PubMed:14603310, PubMed:16226253). Detected in heart (PubMed:2540808).
CC       {ECO:0000269|PubMed:14603310, ECO:0000269|PubMed:16226253,
CC       ECO:0000269|PubMed:2540808}.
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:0000269|PubMed:14603310,
CC       ECO:0000269|PubMed:16226253}.
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; M13783; AAA30363.1; -; mRNA.
DR   EMBL; M24102; AAA30768.1; -; mRNA.
DR   PIR; A43646; XWBO.
DR   RefSeq; NP_777083.1; NM_174658.2.
DR   PDB; 1OKC; X-ray; 2.20 A; A=2-298.
DR   PDB; 2C3E; X-ray; 2.80 A; A=2-298.
DR   PDBsum; 1OKC; -.
DR   PDBsum; 2C3E; -.
DR   AlphaFoldDB; P02722; -.
DR   SMR; P02722; -.
DR   IntAct; P02722; 1.
DR   STRING; 9913.ENSBTAP00000017580; -.
DR   iPTMnet; P02722; -.
DR   PaxDb; 9913-ENSBTAP00000017580; -.
DR   PeptideAtlas; P02722; -.
DR   Ensembl; ENSBTAT00000017580.3; ENSBTAP00000017580.2; ENSBTAG00000013208.3.
DR   GeneID; 282478; -.
DR   KEGG; bta:282478; -.
DR   CTD; 291; -.
DR   VEuPathDB; HostDB:ENSBTAG00000013208; -.
DR   VGNC; VGNC:34765; SLC25A4.
DR   eggNOG; KOG0749; Eukaryota.
DR   GeneTree; ENSGT00940000154622; -.
DR   HOGENOM; CLU_015166_12_0_1; -.
DR   InParanoid; P02722; -.
DR   OMA; AWWMAGN; -.
DR   OrthoDB; 1330359at2759; -.
DR   TreeFam; TF300743; -.
DR   Reactome; R-BTA-1268020; Mitochondrial protein import.
DR   Reactome; R-BTA-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR   EvolutionaryTrace; P02722; -.
DR   Proteomes; UP000009136; Chromosome 27.
DR   Bgee; ENSBTAG00000013208; Expressed in cardiac ventricle and 103 other cell types or tissues.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR   GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR   GO; GO:0005471; F:ATP:ADP antiporter activity; ISS:UniProtKB.
DR   GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; ISS:UniProtKB.
DR   GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB.
DR   GO; GO:0015866; P:ADP transport; ISS:UniProtKB.
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:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IBA:GO_Central.
DR   GO; GO:1901526; P:positive regulation of mitophagy; ISS:UniProtKB.
DR   GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB.
DR   Gene3D; 1.50.40.10; Mitochondrial carrier domain; 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; ADP,ATP CARRIER PROTEIN 1-RELATED-RELATED; 1.
DR   PANTHER; PTHR45635:SF32; ADP_ATP TRANSLOCASE 1; 1.
DR   Pfam; PF00153; Mito_carr; 3.
DR   PRINTS; PR00927; ADPTRNSLCASE.
DR   PRINTS; PR00926; MITOCARRIER.
DR   SUPFAM; SSF103506; Mitochondrial carrier; 1.
DR   PROSITE; PS50920; SOLCAR; 3.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Antiport; Direct protein sequencing; Membrane;
KW   Methylation; 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|PubMed:7076130"
FT   CHAIN           2..298
FT                   /note="ADP/ATP translocase 1"
FT                   /id="PRO_0000090573"
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:0000269|PubMed:14603310,
FT                   ECO:0000269|PubMed:16226253"
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:0000269|PubMed:14603310,
FT                   ECO:0000269|PubMed:16226253"
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:0000269|PubMed:14603310,
FT                   ECO:0000269|PubMed:16226253"
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:0000269|PubMed:14603310,
FT                   ECO:0000269|PubMed:16226253"
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:0000269|PubMed:14603310,
FT                   ECO:0000269|PubMed:16226253"
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:0000269|PubMed:14603310,
FT                   ECO:0000269|PubMed:16226253"
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:0000305"
FT   BINDING         80
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000305|PubMed:14603310"
FT   BINDING         92
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000305|PubMed:14603310"
FT   BINDING         235
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000305|PubMed:14603310"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000269|PubMed:7076130"
FT   MOD_RES         7
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05962"
FT   MOD_RES         52
FT                   /note="N6,N6,N6-trimethyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05962"
FT   MOD_RES         52
FT                   /note="N6-methyllysine"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         147
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P48962"
FT   MOD_RES         160
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05962"
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"
FT   HELIX           5..25
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           27..38
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           39..41
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           47..49
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           54..65
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           67..71
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   TURN            72..74
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           75..100
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   TURN            105..107
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           109..143
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   TURN            149..151
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           157..168
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           170..173
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   TURN            174..176
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           177..200
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           204..206
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           210..239
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   TURN            240..243
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           246..248
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           254..265
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           267..271
FT                   /evidence="ECO:0007829|PDB:1OKC"
FT   HELIX           274..292
FT                   /evidence="ECO:0007829|PDB:1OKC"
SQ   SEQUENCE   298 AA;  32967 MW;  AAE851F8406479C2 CRC64;
     MSDQALSFLK DFLAGGVAAA ISKTAVAPIE RVKLLLQVQH ASKQISAEKQ YKGIIDCVVR
     IPKEQGFLSF WRGNLANVIR YFPTQALNFA FKDKYKQIFL GGVDRHKQFW RYFAGNLASG
     GAAGATSLCF VYPLDFARTR LAADVGKGAA QREFTGLGNC ITKIFKSDGL RGLYQGFNVS
     VQGIIIYRAA YFGVYDTAKG MLPDPKNVHI IVSWMIAQTV TAVAGLVSYP FDTVRRRMMM
     QSGRKGADIM YTGTVDCWRK IAKDEGPKAF FKGAWSNVLR GMGGAFVLVL YDEIKKFV
//