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 27-MAR-2024, entry version 245. 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, GN ECO:0000312|HGNC:HGNC:10990}; GN Synonyms=AAC1 {ECO:0000250|UniProtKB:P48962}, ANT1 GN {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 328. DR DIP; DIP-33116N; -. DR IntAct; P12235; 53. 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 MoonProt; 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; 9606-ENSP00000281456; -. DR PeptideAtlas; P12235; -. DR ProteomicsDB; 52836; -. DR Pumba; P12235; -. DR TopDownProteomics; P12235; -. DR Antibodypedia; 28911; 199 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 AGR; HGNC:10990; -. 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; AWWMAGN; -. DR OrthoDB; 1330359at2759; -. 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; 14 hits in 1168 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 209 other cell types or tissues. DR ExpressionAtlas; P12235; baseline and differential. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB. DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. 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; 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. DR Genevisible; P12235; HS. 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 //