ADT1_RABIT
ID ADT1_RABIT Reviewed; 298 AA.
AC O46373;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=ADP/ATP translocase 1 {ECO:0000305};
DE AltName: Full=30 kDa calsequestrin-binding protein {ECO:0000303|PubMed:9794793};
DE Short=30 kDa CSQ-binding protein {ECO:0000303|PubMed:9794793};
DE AltName: Full=ADP,ATP carrier protein 1 {ECO:0000250|UniProtKB:P48962};
DE AltName: Full=Adenine nucleotide translocator 1 {ECO:0000250|UniProtKB:P12235};
DE Short=ANT 1 {ECO:0000250|UniProtKB:P12235};
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:9794793};
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 TISSUE=Skeletal muscle;
RX PubMed=9794793; DOI=10.1042/bj3350541;
RA Yamaguchi N., Kasai M.;
RT "Identification of 30 kDa calsequestrin-binding protein, which regulates
RT calcium release from sarcoplasmic reticulum of rabbit skeletal muscle.";
RL Biochem. J. 335:541-547(1998).
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. Plays a
CC role in mitochondrial uncoupling by acting as a proton transporter:
CC proton transport uncouples the proton flows via the electron transport
CC chain and ATP synthase to reduce the efficiency of ATP production and
CC cause mitochondrial thermogenesis. Proton transporter activity is
CC inhibited by ADP:ATP antiporter activity, suggesting that SLC25A4/ANT1
CC acts as a master regulator of mitochondrial energy output by
CC maintaining a delicate balance between ATP production (ADP:ATP
CC antiporter activity) and thermogenesis (proton transporter activity).
CC Proton transporter activity requires free fatty acids as cofactor, but
CC does not transport it. Probably mediates mitochondrial uncoupling in
CC tissues that do not express UCP1. 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. It is however unclear if SLC25A4/ANT1
CC constitutes a pore-forming component of mPTP or regulates it (By
CC similarity). Acts as a regulator of mitophagy independently of ADP:ATP
CC antiporter activity: promotes mitophagy via interaction with TIMM44,
CC 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 -!- 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 (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:P02722}; 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; AB009386; BAA23777.1; -; mRNA.
DR RefSeq; NP_001076155.1; NM_001082686.1.
DR RefSeq; XP_002715967.1; XM_002715921.3.
DR AlphaFoldDB; O46373; -.
DR SMR; O46373; -.
DR STRING; 9986.ENSOCUP00000002239; -.
DR PRIDE; O46373; -.
DR Ensembl; ENSOCUT00000002593; ENSOCUP00000002239; ENSOCUG00000002594.
DR GeneID; 100009414; -.
DR GeneID; 100349768; -.
DR KEGG; ocu:100009414; -.
DR KEGG; ocu:100349768; -.
DR CTD; 291; -.
DR eggNOG; KOG0749; Eukaryota.
DR GeneTree; ENSGT00940000154622; -.
DR HOGENOM; CLU_015166_12_0_1; -.
DR InParanoid; O46373; -.
DR OMA; YDGIVEC; -.
DR OrthoDB; 870903at2759; -.
DR TreeFam; TF300743; -.
DR Proteomes; UP000001811; Chromosome 2.
DR Bgee; ENSOCUG00000002594; Expressed in heart and 16 other tissues.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS: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: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 2: Evidence at transcript level;
KW Acetylation; Antiport; Membrane; Methylation; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Reference proteome; Repeat;
KW S-nitrosylation; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT CHAIN 2..298
FT /note="ADP/ATP translocase 1"
FT /id="PRO_0000090576"
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-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P02722"
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 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"
SQ SEQUENCE 298 AA; 32901 MW; CAEA32C88164AD78 CRC64;
MSDQALSFLK DFLAGGVAAA VSKTAVAPIE RVKLLLQVQH ASKQISAEKQ YKGIIDCVVR
IPKEQGFLSF WRGNLANVIR YFPTQALNFA FKDKYKQIFL GGVDRHKQFW RYFAGNLASG
GAAGATSLCF VYPLDFARTR LAADVGKGAA QREFSGLGNC LTKIFKSDGL RGLYQGFNVS
VQGIIIYRAA YFGVYDTAKG MLPDPKNVHI IVSWMIAQTV TAVAGLVSYP FDTVRRRMMM
QSGRKGADIM YTGTVDCWKK IAKDEGAKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYV
