ADT1_HUMAN
ID ADT1_HUMAN Reviewed; 298 AA.
AC P12235; D3DP59;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=ADP/ATP translocase 1 {ECO:0000305};
DE AltName: Full=ADP,ATP carrier protein 1 {ECO:0000250|UniProtKB:P48962};
DE AltName: Full=ADP,ATP carrier protein, heart/skeletal muscle isoform T1 {ECO:0000303|PubMed:2541251};
DE AltName: Full=Adenine nucleotide translocator 1 {ECO:0000303|PubMed:2823266};
DE Short=ANT 1 {ECO:0000303|PubMed:2823266};
DE AltName: Full=Solute carrier family 25 member 4 {ECO:0000305};
GN Name=SLC25A4 {ECO:0000303|PubMed:25732997, ECO:0000312|HGNC:HGNC:10990};
GN Synonyms=AAC1 {ECO:0000250|UniProtKB:P48962},
GN ANT1 {ECO:0000303|PubMed:2823266};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2823266; DOI=10.1073/pnas.84.21.7580;
RA Neckelmann N., Li K., Wade R.P., Shuster R., Wallace D.C.;
RT "cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a
RT leader peptide, divergence from a fibroblast translocator cDNA, and
RT coevolution with mitochondrial DNA genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7580-7584(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2541251; DOI=10.1016/0022-2836(89)90477-4;
RA Cozens A.L., Runswick M.J., Walker J.E.;
RT "DNA sequences of two expressed nuclear genes for human mitochondrial
RT ADP/ATP translocase.";
RL J. Mol. Biol. 206:261-280(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2547778; DOI=10.1016/s0021-9258(18)71632-3;
RA Li K., Warner C.K., Hodge J.A., Minoshima S., Kudoh J., Fukuyama R.,
RA Maekawa M., Shimizu Y., Shimizu N., Wallace D.C.;
RT "A human muscle adenine nucleotide translocator gene has four exons, is
RT located on chromosome 4, and is differentially expressed.";
RL J. Biol. Chem. 264:13998-14004(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=20843780; DOI=10.1093/nar/gkq750;
RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R.,
RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M.,
RA Speed T.P., Scharfe C.;
RT "Identification of rare DNA variants in mitochondrial disorders with
RT improved array-based sequencing.";
RL Nucleic Acids Res. 39:44-58(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, Mammary gland, and PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-37.
RC TISSUE=Liver;
RX PubMed=2829183; DOI=10.1073/pnas.85.2.377;
RA Houldsworth J., Attardi G.;
RT "Two distinct genes for ADP/ATP translocase are expressed at the mRNA level
RT in adult human liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:377-381(1988).
RN [8]
RP PROTEIN SEQUENCE OF 2-31; 34-43; 64-92; 141-147; 189-199 AND 273-296,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT GLY-2, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [9]
RP INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION).
RX PubMed=16120388; DOI=10.1016/j.mito.2004.06.012;
RA Deniaud A., Brenner C., Kroemer G.;
RT "Mitochondrial membrane permeabilization by HIV-1 Vpr.";
RL Mitochondrion 4:223-233(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP AND CHARACTERIZATION OF VARIANTS PEOA2 PRO-114 AND MET-289.
RX PubMed=21586654; DOI=10.1093/hmg/ddr200;
RA Kawamata H., Tiranti V., Magrane J., Chinopoulos C., Manfredi G.;
RT "adPEO mutations in ANT1 impair ADP-ATP translocation in muscle
RT mitochondria.";
RL Hum. Mol. Genet. 20:2964-2974(2011).
RN [13]
RP INVOLVEMENT IN MTDPS12B.
RX PubMed=22187496; DOI=10.1136/jmedgenet-2011-100504;
RA Echaniz-Laguna A., Chassagne M., Ceresuela J., Rouvet I., Padet S.,
RA Acquaviva C., Nataf S., Vinzio S., Bozon D., Mousson de Camaret B.;
RT "Complete loss of expression of the ANT1 gene causing cardiomyopathy and
RT myopathy.";
RL J. Med. Genet. 49:146-150(2012).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP FUNCTION, INVOLVEMENT IN MTDPS12A, VARIANTS MTDPS12A HIS-80 AND GLY-235,
RP CHARACTERIZATION OF VARIANTS MTDPS12A HIS-80 AND GLY-235, CHARACTERIZATION
RP OF VARIANTS PEOA2 ASP-90; PRO-98; GLY-104 AND PRO-114, AND CHARACTERIZATION
RP OF VARIANTS MTDPS12B ASP-123 AND PRO-236.
RX PubMed=27693233; DOI=10.1016/j.ajhg.2016.08.014;
RA Thompson K., Majd H., Dallabona C., Reinson K., King M.S., Alston C.L.,
RA He L., Lodi T., Jones S.A., Fattal-Valevski A., Fraenkel N.D., Saada A.,
RA Haham A., Isohanni P., Vara R., Barbosa I.A., Simpson M.A., Deshpande C.,
RA Puusepp S., Bonnen P.E., Rodenburg R.J., Suomalainen A., Ounap K.,
RA Elpeleg O., Ferrero I., McFarland R., Kunji E.R., Taylor R.W.;
RT "Recurrent de novo dominant mutations in SLC25A4 cause severe early-onset
RT mitochondrial disease and loss of mitochondrial DNA copy number.";
RL Am. J. Hum. Genet. 99:860-876(2016).
RN [16]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=27641616; DOI=10.1038/srep33516;
RA Marginedas-Freixa I., Hattab C., Bouyer G., Halle F., Chene A.,
RA Lefevre S.D., Cambot M., Cueff A., Schmitt M., Gamain B., Lacapere J.J.,
RA Egee S., Bihel F., Le Van Kim C., Ostuni M.A.;
RT "TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to
RT the inhibition of P. falciparum growth in human blood.";
RL Sci. Rep. 6:33516-33516(2016).
RN [17]
RP FUNCTION, AND INTERACTION WITH ARHGAP11B.
RX PubMed=31883789; DOI=10.1016/j.neuron.2019.11.027;
RA Namba T., Doczi J., Pinson A., Xing L., Kalebic N., Wilsch-Braeuninger M.,
RA Long K.R., Vaid S., Lauer J., Bogdanova A., Borgonovo B., Shevchenko A.,
RA Keller P., Drechsel D., Kurzchalia T., Wimberger P., Chinopoulos C.,
RA Huttner W.B.;
RT "Human-specific ARHGAP11B acts in mitochondria to expand neocortical
RT progenitors by glutaminolysis.";
RL Neuron 105:867-881(2020).
RN [18]
RP VARIANTS PEOA2 PRO-114 AND MET-289.
RX PubMed=10926541; DOI=10.1126/science.289.5480.782;
RA Kaukonen J., Juselius J.K., Tiranti V., Kyttala A., Zeviani M., Comi G.P.,
RA Keranen J., Peltonen L., Suomalainen A.;
RT "Role of adenine nucleotide translocator 1 in mtDNA maintenance.";
RL Science 289:782-785(2000).
RN [19]
RP VARIANT PEOA2 PRO-98.
RX PubMed=11756613; DOI=10.1212/wnl.57.12.2295;
RA Napoli L., Bordoni A., Zeviani M., Hadjigeorgiou G.M., Sciacco M.,
RA Tiranti V., Terentiou A., Moggio M., Papadimitriou A., Scarlato G.,
RA Comi G.P.;
RT "A novel missense adenine nucleotide translocator-1 gene mutation in a
RT Greek adPEO family.";
RL Neurology 57:2295-2298(2001).
RN [20]
RP VARIANT PEOA2 GLY-104.
RX PubMed=12112115; DOI=10.1002/ana.10172;
RA Komaki H., Fukazawa T., Houzen H., Yoshida K., Nonaka I., Goto Y.;
RT "A novel D104G mutation in the adenine nucleotide translocator 1 gene in
RT autosomal dominant progressive external ophthalmoplegia patients with
RT mitochondrial DNA with multiple deletions.";
RL Ann. Neurol. 51:645-648(2002).
RN [21]
RP VARIANT PEOA2 MET-289.
RX PubMed=12707443; DOI=10.1212/01.wnl.0000056088.09408.3c;
RA Agostino A., Valletta L., Chinnery P.F., Ferrari G., Carrara F.,
RA Taylor R.W., Schaefer A.M., Turnbull D.M., Tiranti V., Zeviani M.;
RT "Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external
RT ophthalmoplegia (PEO).";
RL Neurology 60:1354-1356(2003).
RN [22]
RP VARIANT MTDPS12B ASP-123.
RX PubMed=16155110; DOI=10.1093/hmg/ddi341;
RA Palmieri L., Alberio S., Pisano I., Lodi T., Meznaric-Petrusa M., Zidar J.,
RA Santoro A., Scarcia P., Fontanesi F., Lamantea E., Ferrero I., Zeviani M.;
RT "Complete loss-of-function of the heart/muscle-specific adenine nucleotide
RT translocator is associated with mitochondrial myopathy and
RT cardiomyopathy.";
RL Hum. Mol. Genet. 14:3079-3088(2005).
RN [23]
RP VARIANT PEOA2 ASP-90.
RX PubMed=15792871; DOI=10.1016/j.nmd.2004.12.004;
RA Deschauer M., Hudson G., Mueller T., Taylor R.W., Chinnery P.F., Zierz S.;
RT "A novel ANT1 gene mutation with probable germline mosaicism in autosomal
RT dominant progressive external ophthalmoplegia.";
RL Neuromuscul. Disord. 15:311-315(2005).
RN [24]
RP VARIANTS PEOA2 PRO-98 AND PRO-114.
RX PubMed=18575922; DOI=10.1007/s00415-008-0926-3;
RA Virgilio R., Ronchi D., Hadjigeorgiou G.M., Bordoni A., Saladino F.,
RA Moggio M., Adobbati L., Kafetsouli D., Tsironi E., Previtali S.,
RA Papadimitriou A., Bresolin N., Comi G.P.;
RT "Novel Twinkle (PEO1) gene mutations in Mendelian progressive external
RT ophthalmoplegia.";
RL J. Neurol. 255:1384-1391(2008).
RN [25]
RP VARIANT MTDPS12B PRO-236.
RX PubMed=25732997; DOI=10.1007/8904_2015_409;
RA Koerver-Keularts I.M., de Visser M., Bakker H.D., Wanders R.J.,
RA Vansenne F., Scholte H.R., Dorland L., Nicolaes G.A., Spaapen L.M.,
RA Smeets H.J., Hendrickx A.T., van den Bosch B.J.;
RT "Two novel mutations in the SLC25A4 gene in a patient with mitochondrial
RT myopathy.";
RL JIMD Rep. 22:39-45(2015).
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 (PubMed:21586654, PubMed:27693233). Cycles between the
CC cytoplasmic-open state (c-state) and the matrix-open state (m-state):
CC operates by the alternating access mechanism with a single substrate-
CC binding site intermittently exposed to either the cytosolic (c-state)
CC or matrix (m-state) side of the inner mitochondrial membrane (By
CC similarity). In addition to its ADP:ATP antiporter activity, also
CC involved in mitochondrial uncoupling and mitochondrial permeability
CC transition pore (mPTP) activity (PubMed:31883789). Plays a role in
CC mitochondrial uncoupling by acting as a proton transporter: proton
CC transport uncouples the proton flows via the electron transport chain
CC and ATP synthase to reduce the efficiency of ATP production and cause
CC mitochondrial thermogenesis (By similarity). Proton transporter
CC activity is inhibited by ADP:ATP antiporter activity, suggesting that
CC SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output
CC by maintaining a delicate balance between ATP production (ADP:ATP
CC antiporter activity) and thermogenesis (proton transporter activity)
CC (By similarity). Proton transporter activity requires free fatty acids
CC as cofactor, but does not transport it (By similarity). Also plays a
CC key role in mPTP opening, a non-specific pore that enables free passage
CC of the mitochondrial membranes to solutes of up to 1.5 kDa, and which
CC contributes to cell death (PubMed:31883789). 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:21586654, ECO:0000269|PubMed:27693233,
CC ECO:0000269|PubMed:31883789}.
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:0000269|PubMed:21586654};
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)
CC (PubMed:21586654). Proton transporter activity is inhibited by ADP:ATP
CC antiporter activity (By similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:21586654}.
CC -!- SUBUNIT: Monomer (By similarity). Found in a complex with ARL2, ARL2BP
CC and SLC25A4/ANT1 (By similarity). Interacts with ARL2BP (By
CC similarity). Interacts with ARHGAP11B, thereby inhibiting the
CC mitochondrial permeability transition pore (mPTP) (PubMed:31883789).
CC Interacts 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:P02722,
CC ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:31883789}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Vpr.
CC {ECO:0000269|PubMed:16120388}.
CC -!- INTERACTION:
CC P12235; Q5S007: LRRK2; NbExp=2; IntAct=EBI-359074, EBI-5323863;
CC P12235; P22736-1: NR4A1; NbExp=2; IntAct=EBI-359074, EBI-16085263;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:21586654}; Multi-pass membrane protein
CC {ECO:0000255}. Membrane {ECO:0000269|PubMed:27641616}; 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 (PubMed:27641616).
CC {ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:27641616}.
CC -!- TISSUE SPECIFICITY: Expressed in erythrocytes (at protein level).
CC {ECO:0000269|PubMed:27641616}.
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 -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA
CC deletions, autosomal dominant, 2 (PEOA2) [MIM:609283]: A disorder
CC characterized by progressive weakness of ocular muscles and levator
CC muscle of the upper eyelid. In a minority of cases, it is associated
CC with skeletal myopathy, which predominantly involves axial or proximal
CC muscles and which causes abnormal fatigability and even permanent
CC muscle weakness. Ragged-red fibers and atrophy are found on muscle
CC biopsy. A large proportion of chronic ophthalmoplegias are associated
CC with other symptoms, leading to a multisystemic pattern of this
CC disease. Additional symptoms are variable, and may include cataracts,
CC hearing loss, sensory axonal neuropathy, ataxia, depression,
CC hypogonadism, and parkinsonism. {ECO:0000269|PubMed:10926541,
CC ECO:0000269|PubMed:11756613, ECO:0000269|PubMed:12112115,
CC ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:15792871,
CC ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:21586654,
CC ECO:0000269|PubMed:27693233}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type
CC (MTDPS12B) [MIM:615418]: An autosomal recessive mitochondrial disorder
CC characterized by childhood onset of slowly progressive hypertrophic
CC cardiomyopathy and generalized skeletal myopathy resulting in exercise
CC intolerance and, in some patients, muscle weakness and atrophy.
CC Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and
CC accumulation of abnormal mitochondria. {ECO:0000269|PubMed:16155110,
CC ECO:0000269|PubMed:22187496, ECO:0000269|PubMed:25732997,
CC ECO:0000269|PubMed:27693233}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type
CC (MTDPS12A) [MIM:617184]: An autosomal dominant mitochondrial disorder
CC characterized by severe hypotonia due to mitochondrial dysfunction
CC apparent at birth. Affected infants have respiratory insufficiency
CC requiring mechanical ventilation and have poor or no motor development.
CC Many die in infancy, and those that survive have profound hypotonia
CC with significant muscle weakness and inability to walk independently.
CC Some patients develop hypertrophic cardiomyopathy. Muscle samples show
CC mtDNA depletion and severe combined mitochondrial respiratory chain
CC deficiencies. {ECO:0000269|PubMed:27693233}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; J02966; AAA61223.1; -; mRNA.
DR EMBL; J04982; AAA51736.1; -; Genomic_DNA.
DR EMBL; HQ206346; ADP92294.1; -; Genomic_DNA.
DR EMBL; HQ206347; ADP92295.1; -; Genomic_DNA.
DR EMBL; HQ206348; ADP92296.1; -; Genomic_DNA.
DR EMBL; HQ206349; ADP92297.1; -; Genomic_DNA.
DR EMBL; HQ206350; ADP92298.1; -; Genomic_DNA.
DR EMBL; HQ206351; ADP92299.1; -; Genomic_DNA.
DR EMBL; HQ206352; ADP92300.1; -; Genomic_DNA.
DR EMBL; HQ206353; ADP92301.1; -; Genomic_DNA.
DR EMBL; HQ206354; ADP92302.1; -; Genomic_DNA.
DR EMBL; HQ206355; ADP92303.1; -; Genomic_DNA.
DR EMBL; HQ206356; ADP92304.1; -; Genomic_DNA.
DR EMBL; HQ206357; ADP92305.1; -; Genomic_DNA.
DR EMBL; HQ206358; ADP92306.1; -; Genomic_DNA.
DR EMBL; HQ206359; ADP92307.1; -; Genomic_DNA.
DR EMBL; HQ206360; ADP92308.1; -; Genomic_DNA.
DR EMBL; HQ206361; ADP92309.1; -; Genomic_DNA.
DR EMBL; HQ206362; ADP92310.1; -; Genomic_DNA.
DR EMBL; HQ206363; ADP92311.1; -; Genomic_DNA.
DR EMBL; HQ206364; ADP92312.1; -; Genomic_DNA.
DR EMBL; HQ206365; ADP92313.1; -; Genomic_DNA.
DR EMBL; HQ206366; ADP92314.1; -; Genomic_DNA.
DR EMBL; HQ206367; ADP92315.1; -; Genomic_DNA.
DR EMBL; HQ206368; ADP92316.1; -; Genomic_DNA.
DR EMBL; HQ206369; ADP92317.1; -; Genomic_DNA.
DR EMBL; HQ206370; ADP92318.1; -; Genomic_DNA.
DR EMBL; HQ206371; ADP92319.1; -; Genomic_DNA.
DR EMBL; HQ206372; ADP92320.1; -; Genomic_DNA.
DR EMBL; HQ206373; ADP92321.1; -; Genomic_DNA.
DR EMBL; HQ206374; ADP92322.1; -; Genomic_DNA.
DR EMBL; HQ206375; ADP92323.1; -; Genomic_DNA.
DR EMBL; HQ206376; ADP92324.1; -; Genomic_DNA.
DR EMBL; HQ206377; ADP92325.1; -; Genomic_DNA.
DR EMBL; HQ206378; ADP92326.1; -; Genomic_DNA.
DR EMBL; HQ206379; ADP92327.1; -; Genomic_DNA.
DR EMBL; HQ206380; ADP92328.1; -; Genomic_DNA.
DR EMBL; HQ206381; ADP92329.1; -; Genomic_DNA.
DR EMBL; HQ206382; ADP92330.1; -; Genomic_DNA.
DR EMBL; HQ206383; ADP92331.1; -; Genomic_DNA.
DR EMBL; HQ206384; ADP92332.1; -; Genomic_DNA.
DR EMBL; HQ206385; ADP92333.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04655.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04656.1; -; Genomic_DNA.
DR EMBL; BC008664; AAH08664.1; -; mRNA.
DR EMBL; BC061589; AAH61589.1; -; mRNA.
DR EMBL; BC063643; AAH63643.1; -; mRNA.
DR EMBL; J03593; AAA36751.1; -; mRNA.
DR CCDS; CCDS34114.1; -.
DR PIR; A44778; A44778.
DR RefSeq; NP_001142.2; NM_001151.3.
DR AlphaFoldDB; P12235; -.
DR SMR; P12235; -.
DR BioGRID; 106788; 311.
DR DIP; DIP-33116N; -.
DR IntAct; P12235; 51.
DR MINT; P12235; -.
DR STRING; 9606.ENSP00000281456; -.
DR DrugBank; DB01736; [3-(Dodecanoylamino)Propyl](Hydroxy)Dimethylammonium.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB02426; Carboxyatractyloside.
DR DrugBank; DB00720; Clodronic acid.
DR DrugBank; DB04178; Di-Stearoyl-3-Sn-Phosphatidylcholine.
DR DrugBank; DB01077; Etidronic acid.
DR DrugBank; DB03429; Tetrastearoyl cardiolipin.
DR DrugCentral; P12235; -.
DR TCDB; 2.A.29.1.2; the mitochondrial carrier (mc) family.
DR GlyGen; P12235; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P12235; -.
DR MetOSite; P12235; -.
DR PhosphoSitePlus; P12235; -.
DR SwissPalm; P12235; -.
DR BioMuta; SLC25A4; -.
DR DMDM; 113455; -.
DR EPD; P12235; -.
DR jPOST; P12235; -.
DR MassIVE; P12235; -.
DR MaxQB; P12235; -.
DR PaxDb; P12235; -.
DR PeptideAtlas; P12235; -.
DR PRIDE; P12235; -.
DR ProteomicsDB; 52836; -.
DR TopDownProteomics; P12235; -.
DR Antibodypedia; 28911; 167 antibodies from 24 providers.
DR DNASU; 291; -.
DR Ensembl; ENST00000281456.11; ENSP00000281456.5; ENSG00000151729.11.
DR GeneID; 291; -.
DR KEGG; hsa:291; -.
DR MANE-Select; ENST00000281456.11; ENSP00000281456.5; NM_001151.4; NP_001142.2.
DR UCSC; uc003ixd.4; human.
DR CTD; 291; -.
DR DisGeNET; 291; -.
DR GeneCards; SLC25A4; -.
DR HGNC; HGNC:10990; SLC25A4.
DR HPA; ENSG00000151729; Group enriched (heart muscle, skeletal muscle, tongue).
DR MalaCards; SLC25A4; -.
DR MIM; 103220; gene.
DR MIM; 609283; phenotype.
DR MIM; 615418; phenotype.
DR MIM; 617184; phenotype.
DR neXtProt; NX_P12235; -.
DR OpenTargets; ENSG00000151729; -.
DR Orphanet; 254892; Autosomal dominant progressive external ophthalmoplegia.
DR Orphanet; 1369; Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome.
DR PharmGKB; PA35866; -.
DR VEuPathDB; HostDB:ENSG00000151729; -.
DR eggNOG; KOG0749; Eukaryota.
DR GeneTree; ENSGT00940000154622; -.
DR InParanoid; P12235; -.
DR OMA; YDGIVEC; -.
DR OrthoDB; 870903at2759; -.
DR PhylomeDB; P12235; -.
DR TreeFam; TF300743; -.
DR PathwayCommons; P12235; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR Reactome; R-HSA-180897; Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization.
DR Reactome; R-HSA-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR SignaLink; P12235; -.
DR SIGNOR; P12235; -.
DR BioGRID-ORCS; 291; 12 hits in 1081 CRISPR screens.
DR ChiTaRS; SLC25A4; human.
DR GeneWiki; SLC25A4; -.
DR GenomeRNAi; 291; -.
DR Pharos; P12235; Tbio.
DR PRO; PR:P12235; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P12235; protein.
DR Bgee; ENSG00000151729; Expressed in left ventricle myocardium and 207 other tissues.
DR ExpressionAtlas; P12235; baseline and differential.
DR Genevisible; P12235; HS.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0015207; F:adenine transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0005471; F:ATP:ADP antiporter activity; IDA:UniProtKB.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; ISS:UniProtKB.
DR GO; GO:0015078; F:proton transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB.
DR GO; GO:0015866; P:ADP transport; IMP:UniProtKB.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IEA:Ensembl.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR GO; GO:0140021; P:mitochondrial ADP transmembrane transport; IDA:UniProtKB.
DR GO; GO:1990544; P:mitochondrial ATP transmembrane transport; IDA:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; TAS:ProtInc.
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; IMP:BHF-UCL.
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 Acetylation; Antiport; Cardiomyopathy; Direct protein sequencing;
KW Disease variant; Host-virus interaction; Membrane; Methylation;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Primary mitochondrial disease; Progressive external ophthalmoplegia;
KW Reference proteome; Repeat; S-nitrosylation; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8"
FT CHAIN 2..298
FT /note="ADP/ATP translocase 1"
FT /id="PRO_0000090574"
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:0000269|PubMed:27693233"
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.8"
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"
FT VARIANT 80
FT /note="R -> H (in MTDPS12A; decreased function in ADP
FT transport; dbSNP:rs886041081)"
FT /evidence="ECO:0000269|PubMed:27693233"
FT /id="VAR_078071"
FT VARIANT 90
FT /note="A -> D (in PEOA2; decreased function in ADP
FT transport)"
FT /evidence="ECO:0000269|PubMed:15792871,
FT ECO:0000269|PubMed:27693233"
FT /id="VAR_038814"
FT VARIANT 98
FT /note="L -> P (in PEOA2; decreased function in ADP
FT transport; dbSNP:rs104893876)"
FT /evidence="ECO:0000269|PubMed:11756613,
FT ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:27693233"
FT /id="VAR_022459"
FT VARIANT 104
FT /note="D -> G (in PEOA2; decreased function in ADP
FT transport; dbSNP:rs28999114)"
FT /evidence="ECO:0000269|PubMed:12112115,
FT ECO:0000269|PubMed:27693233"
FT /id="VAR_022460"
FT VARIANT 114
FT /note="A -> P (in PEOA2; decreased function in ADP
FT transport; inverted direction of ADP:ATP transport, with
FT ATP entering the mitochondrial matrix; dbSNP:rs104893873)"
FT /evidence="ECO:0000269|PubMed:10926541,
FT ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:21586654,
FT ECO:0000269|PubMed:27693233"
FT /id="VAR_012111"
FT VARIANT 123
FT /note="A -> D (in MTDPS12B; loss of function in ADP
FT transport; dbSNP:rs121912683)"
FT /evidence="ECO:0000269|PubMed:16155110,
FT ECO:0000269|PubMed:27693233"
FT /id="VAR_038815"
FT VARIANT 235
FT /note="R -> G (in MTDPS12A; severely decreased function in
FT ADP transport; dbSNP:rs886041082)"
FT /evidence="ECO:0000269|PubMed:27693233"
FT /id="VAR_078072"
FT VARIANT 236
FT /note="R -> P (in MTDPS12B; loss of function in ADP
FT transport; dbSNP:rs770816416)"
FT /evidence="ECO:0000269|PubMed:25732997,
FT ECO:0000269|PubMed:27693233"
FT /id="VAR_078073"
FT VARIANT 289
FT /note="V -> M (in PEOA2; inverted direction of ADP:ATP
FT transport, with ATP entering the mitochondrial matrix;
FT dbSNP:rs104893874)"
FT /evidence="ECO:0000269|PubMed:10926541,
FT ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:21586654"
FT /id="VAR_012112"
FT CONFLICT 16
FT /note="G -> A (in Ref. 1; AAA61223)"
FT /evidence="ECO:0000305"
FT CONFLICT 147..149
FT /note="KGA -> RR (in Ref. 1; AAA61223)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="V -> L (in Ref. 1; AAA61223)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 298 AA; 33064 MW; 59F0DFAEC4E7CFBB CRC64;
MGDHAWSFLK DFLAGGVAAA VSKTAVAPIE RVKLLLQVQH ASKQISAEKQ YKGIIDCVVR
IPKEQGFLSF WRGNLANVIR YFPTQALNFA FKDKYKQLFL GGVDRHKQFW RYFAGNLASG
GAAGATSLCF VYPLDFARTR LAADVGKGAA QREFHGLGDC IIKIFKSDGL RGLYQGFNVS
VQGIIIYRAA YFGVYDTAKG MLPDPKNVHI FVSWMIAQSV TAVAGLVSYP FDTVRRRMMM
QSGRKGADIM YTGTVDCWRK IAKDEGAKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYV
