ADT1_BOVIN
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 03-AUG-2022, entry version 174.
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},
GN ANT1 {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; P02722; -.
DR PeptideAtlas; P02722; -.
DR PRIDE; P02722; -.
DR Ensembl; ENSBTAT00000017580; ENSBTAP00000017580; ENSBTAG00000013208.
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; YDGIVEC; -.
DR OrthoDB; 870903at2759; -.
DR TreeFam; TF300743; -.
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 tissues.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS: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; -; 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 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
