ADT2_HUMAN
ID ADT2_HUMAN Reviewed; 298 AA.
AC P05141; B2RCV1; O43350;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 7.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=ADP/ATP translocase 2 {ECO:0000305};
DE AltName: Full=ADP,ATP carrier protein 2 {ECO:0000303|PubMed:3031073};
DE AltName: Full=ADP,ATP carrier protein, fibroblast isoform {ECO:0000303|PubMed:2168878};
DE AltName: Full=Adenine nucleotide translocator 2 {ECO:0000303|PubMed:8918809};
DE Short=ANT 2;
DE AltName: Full=Solute carrier family 25 member 5 {ECO:0000305};
DE Contains:
DE RecName: Full=ADP/ATP translocase 2, N-terminally processed;
GN Name=SLC25A5 {ECO:0000312|HGNC:HGNC:10991};
GN Synonyms=AAC2 {ECO:0000250|UniProtKB:P51881},
GN ANT2 {ECO:0000303|PubMed:8918809};
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 [GENOMIC DNA], AND VARIANT ARG-111.
RC TISSUE=Placenta;
RX PubMed=2168878; DOI=10.1016/s0021-9258(17)46187-4;
RA Ku D.-H., Kagan J., Chen S.-T., Chang C.-D., Baserga R., Wurzel J.;
RT "The human fibroblast adenine nucleotide translocator gene. Molecular
RT cloning and sequence.";
RL J. Biol. Chem. 265:16060-16063(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-111.
RX PubMed=3031073; DOI=10.1016/s0021-9258(18)61355-9;
RA Battini R., Ferrari S., Kaczmarek L., Calabretta B., Chen S.T., Baserga R.;
RT "Molecular cloning of a cDNA for a human ADP/ATP carrier which is growth-
RT regulated.";
RL J. Biol. Chem. 262:4355-4358(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-111.
RX PubMed=8918809; DOI=10.1093/nar/24.20.4034;
RA Chen C.N., Su Y., Baybayan P., Siruno A., Nagaraja R., Mazzarella R.,
RA Schlessinger D., Chen E.;
RT "Ordered shotgun sequencing of a 135 kb Xq25 YAC containing ANT2 and four
RT possible genes, including three confirmed by EST matches.";
RL Nucleic Acids Res. 24:4034-4041(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-111.
RC TISSUE=Eye;
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 PROTEIN SEQUENCE OF 2-31; 34-43; 64-92; 141-147; 189-199 AND 273-296,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 2-23; 32-43; 50-60; 64-92; 81-92; 97-106; 112-138;
RP 172-199; 207-235; 245-259 AND 281-295, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT THR-2, METHYLATION AT LYS-52, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 46-297.
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2, CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH AK4.
RX PubMed=19130895; DOI=10.1016/j.biocel.2008.12.002;
RA Liu R., Stroem A.L., Zhai J., Gal J., Bao S., Gong W., Zhu H.;
RT "Enzymatically inactive adenylate kinase 4 interacts with mitochondrial
RT ADP/ATP translocase.";
RL Int. J. Biochem. Cell Biol. 41:1371-1380(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-105 AND LYS-163, AND
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 [15]
RP FUNCTION, AND IDENTIFICATION IN MMXD COMPLEX.
RX PubMed=20797633; DOI=10.1016/j.molcel.2010.07.029;
RA Ito S., Tan L.J., Andoh D., Narita T., Seki M., Hirano Y., Narita K.,
RA Kuraoka I., Hiraoka Y., Tanaka K.;
RT "MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome
RT segregation.";
RL Mol. Cell 39:632-640(2010).
RN [16]
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 [17]
RP MALONYLATION AT LYS-23; LYS-92; LYS-96 AND LYS-147.
RX PubMed=21908771; DOI=10.1074/mcp.m111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W.,
RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J.,
RA Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-52 AND LYS-147, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [22]
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 [23]
RP METHYLATION AT LYS-52.
RX PubMed=31213526; DOI=10.1074/jbc.ra119.009045;
RA Malecki J., Willemen H.L.D.M., Pinto R., Ho A.Y.Y., Moen A., Eijkelkamp N.,
RA Falnes P.O.;
RT "Human FAM173A is a mitochondrial lysine-specific methyltransferase that
RT targets adenine nucleotide translocase and affects mitochondrial
RT respiration.";
RL J. Biol. Chem. 294:11654-11664(2019).
RN [24]
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).
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 (By similarity).
CC Proton transporter activity is inhibited by ADP:ATP antiporter
CC activity, suggesting that SLC25A5/ANT2 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 (By
CC similarity). Probably mediates mitochondrial uncoupling in tissues that
CC 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 (PubMed:31883789). It is however unclear if
CC SLC25A5/ANT2 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). As part of the
CC mitotic spindle-associated MMXD complex it may play a role in
CC chromosome segregation (PubMed:20797633).
CC {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P51881,
CC ECO:0000269|PubMed:20797633, 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:0000250|UniProtKB:P51881};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000250|UniProtKB:P51881};
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:P51881}.
CC -!- SUBUNIT: Monomer (By similarity). Component of the MMXD complex, which
CC includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5/ANT2
CC (PubMed:20797633). Interacts with AK4 (PubMed:19130895). Interacts with
CC ARHGAP11B, thereby inhibiting the mitochondrial permeability transition
CC pore (mPTP) (PubMed:31883789). Interacts with TIMM44; leading to
CC 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:P51881,
CC ECO:0000269|PubMed:19130895, ECO:0000269|PubMed:20797633,
CC ECO:0000269|PubMed:31883789}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Vpr.
CC {ECO:0000269|PubMed:16120388}.
CC -!- INTERACTION:
CC P05141; Q7Z695: ADCK2; NbExp=4; IntAct=EBI-355133, EBI-21505425;
CC P05141; Q5S007: LRRK2; NbExp=2; IntAct=EBI-355133, EBI-5323863;
CC P05141; Q9Y6E7: SIRT4; NbExp=2; IntAct=EBI-355133, EBI-2606540;
CC P05141; Q8N357: SLC35F6; NbExp=2; IntAct=EBI-355133, EBI-713484;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P02722}; Multi-pass membrane protein
CC {ECO:0000255}. Membrane {ECO:0000269|PubMed:27641616}; Multi-pass
CC membrane protein {ECO:0000255}. Note=May localize to non-mitochondrial
CC membranes. {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: Trimethylated by ANTKMT at Lys-52. {ECO:0000269|PubMed:31213526}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; M57424; AAA51737.1; -; Genomic_DNA.
DR EMBL; J02683; AAA35579.1; -; mRNA.
DR EMBL; L78810; AAB39266.1; -; Genomic_DNA.
DR EMBL; AK315292; BAG37698.1; -; mRNA.
DR EMBL; AC004000; AAB96347.1; -; Genomic_DNA.
DR EMBL; BC056160; AAH56160.1; -; mRNA.
DR EMBL; J03591; AAA36749.1; -; mRNA.
DR CCDS; CCDS14578.1; -.
DR PIR; A29132; A29132.
DR RefSeq; NP_001143.2; NM_001152.4.
DR AlphaFoldDB; P05141; -.
DR SMR; P05141; -.
DR BioGRID; 106789; 319.
DR CORUM; P05141; -.
DR DIP; DIP-33873N; -.
DR IntAct; P05141; 184.
DR MINT; P05141; -.
DR STRING; 9606.ENSP00000360671; -.
DR ChEMBL; CHEMBL3709670; -.
DR DrugBank; DB00720; Clodronic acid.
DR DrugBank; DB01077; Etidronic acid.
DR DrugCentral; P05141; -.
DR TCDB; 2.A.29.1.1; the mitochondrial carrier (mc) family.
DR GlyGen; P05141; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P05141; -.
DR MetOSite; P05141; -.
DR PhosphoSitePlus; P05141; -.
DR SwissPalm; P05141; -.
DR BioMuta; SLC25A5; -.
DR DMDM; 317373597; -.
DR EPD; P05141; -.
DR jPOST; P05141; -.
DR MassIVE; P05141; -.
DR MaxQB; P05141; -.
DR PaxDb; P05141; -.
DR PeptideAtlas; P05141; -.
DR PRIDE; P05141; -.
DR ProteomicsDB; 51804; -.
DR TopDownProteomics; P05141; -.
DR Antibodypedia; 29785; 113 antibodies from 24 providers.
DR DNASU; 292; -.
DR Ensembl; ENST00000317881.9; ENSP00000360671.4; ENSG00000005022.6.
DR GeneID; 292; -.
DR KEGG; hsa:292; -.
DR MANE-Select; ENST00000317881.9; ENSP00000360671.4; NM_001152.5; NP_001143.2.
DR UCSC; uc004erh.5; human.
DR CTD; 292; -.
DR DisGeNET; 292; -.
DR GeneCards; SLC25A5; -.
DR HGNC; HGNC:10991; SLC25A5.
DR HPA; ENSG00000005022; Low tissue specificity.
DR MIM; 300150; gene.
DR neXtProt; NX_P05141; -.
DR OpenTargets; ENSG00000005022; -.
DR PharmGKB; PA35867; -.
DR VEuPathDB; HostDB:ENSG00000005022; -.
DR eggNOG; KOG0749; Eukaryota.
DR GeneTree; ENSGT00940000154400; -.
DR HOGENOM; CLU_015166_12_0_1; -.
DR InParanoid; P05141; -.
DR OMA; GYGKWLA; -.
DR OrthoDB; 870903at2759; -.
DR PhylomeDB; P05141; -.
DR TreeFam; TF300743; -.
DR PathwayCommons; P05141; -.
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; P05141; -.
DR BioGRID-ORCS; 292; 180 hits in 704 CRISPR screens.
DR ChiTaRS; SLC25A5; human.
DR GenomeRNAi; 292; -.
DR Pharos; P05141; Tchem.
DR PRO; PR:P05141; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P05141; protein.
DR Bgee; ENSG00000005022; Expressed in renal medulla and 206 other tissues.
DR Genevisible; P05141; HS.
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; IBA:GO_Central.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0071817; C:MMXD complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0000295; F:adenine nucleotide transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0015207; F:adenine transmembrane transporter activity; TAS:ProtInc.
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:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB.
DR GO; GO:0051503; P:adenine nucleotide transport; IMP:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; 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; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP: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 1: Evidence at protein level;
KW Acetylation; Antiport; Chromosome partition; Direct protein sequencing;
KW Host-virus interaction; Membrane; Methylation; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..298
FT /note="ADP/ATP translocase 2"
FT /id="PRO_0000423220"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000269|Ref.7, ECO:0000269|Ref.8,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..298
FT /note="ADP/ATP translocase 2, N-terminally processed"
FT /id="PRO_0000090579"
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 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 2
FT /note="N-acetylthreonine; in ADP/ATP translocase 2, N-
FT terminally processed"
FT /evidence="ECO:0000269|Ref.7, ECO:0000269|Ref.8,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q09073"
FT MOD_RES 23
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000269|PubMed:21908771"
FT MOD_RES 43
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 52
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:31213526,
FT ECO:0007744|PubMed:24129315"
FT MOD_RES 52
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 52
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 92
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000269|PubMed:21908771"
FT MOD_RES 96
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000269|PubMed:21908771"
FT MOD_RES 105
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 105
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 147
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 147
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21908771"
FT MOD_RES 147
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 147
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 163
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 166
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 268
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 268
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT VARIANT 111
FT /note="L -> R (in dbSNP:rs371749)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2168878, ECO:0000269|PubMed:3031073,
FT ECO:0000269|PubMed:8918809"
FT /id="VAR_030039"
FT CONFLICT 6
FT /note="V -> L (in Ref. 2; AAA35579)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="K -> M (in Ref. 4; BAG37698)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="G -> E (in Ref. 2; AAA35579)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="V -> G (in Ref. 9; AAA36749)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 298 AA; 32852 MW; DC53D083E7217AFE CRC64;
MTDAAVSFAK DFLAGGVAAA ISKTAVAPIE RVKLLLQVQH ASKQITADKQ YKGIIDCVVR
IPKEQGVLSF WRGNLANVIR YFPTQALNFA FKDKYKQIFL GGVDKRTQFW LYFAGNLASG
GAAGATSLCF VYPLDFARTR LAADVGKAGA EREFRGLGDC LVKIYKSDGI KGLYQGFNVS
VQGIIIYRAA YFGIYDTAKG MLPDPKNTHI VISWMIAQTV TAVAGLTSYP FDTVRRRMMM
QSGRKGTDIM YTGTLDCWRK IARDEGGKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYT
