ID   TXTP_HUMAN              Reviewed;         311 AA.
AC   P53007; A8K8E8; Q9BSK6;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   11-FEB-2002, sequence version 2.
DT   27-MAR-2024, entry version 210.
DE   RecName: Full=Tricarboxylate transport protein, mitochondrial;
DE   AltName: Full=Citrate transport protein;
DE            Short=CTP;
DE   AltName: Full=Mitochondrial citrate carrier {ECO:0000303|PubMed:29238895};
DE            Short=CIC {ECO:0000303|PubMed:29238895};
DE   AltName: Full=Solute carrier family 25 member 1;
DE   AltName: Full=Tricarboxylate carrier protein;
DE   Flags: Precursor;
GN   Name=SLC25A1; Synonyms=SLC20A3;
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=8666394; DOI=10.1006/geno.1995.9982;
RA   Heisterkamp N., Mulder M.P., Langeveld A., ten Hoeve J., Wang Z., Roe B.,
RA   Groffen J.;
RT   "Localization of the human mitochondrial citrate transporter protein gene
RT   to chromosome 22q11 in the DiGeorge syndrome critical region.";
RL   Genomics 29:451-456(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   TISSUE=Brain;
RX   PubMed=8660975; DOI=10.1006/geno.1996.0191;
RA   Goldmuntz E., Wang Z., Roe B.A., Budarf M.L.;
RT   "Cloning, genomic organization, and chromosomal localization of human
RT   citrate transport protein to the DiGeorge/velocardiofacial syndrome minimal
RT   critical region.";
RL   Genomics 33:271-276(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   [5]
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   [6]
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [8]
RP   FUNCTION, INVOLVEMENT IN CMS23, AND VARIANT CMS23 GLN-247.
RX   PubMed=26870663; DOI=10.3233/jnd-140021;
RA   Chaouch A., Porcelli V., Cox D., Edvardson S., Scarcia P., De Grassi A.,
RA   Pierri C.L., Cossins J., Laval S.H., Griffin H., Mueller J.S.,
RA   Evangelista T., Toepf A., Abicht A., Huebner A., von der Hagen M.,
RA   Bushby K., Straub V., Horvath R., Elpeleg O., Palace J., Senderek J.,
RA   Beeson D., Palmieri L., Lochmueller H.;
RT   "Mutations in the mitochondrial citrate carrier SLC25A1 are associated with
RT   impaired neuromuscular transmission.";
RL   J. Neuromuscul. Dis. 1:75-90(2014).
RN   [9]
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   [10]
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   [11]
RP   FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP   CHARACTERIZATION OF VARIANTS D2L2AD LEU-45; ASP-130; GLN-144; TRP-193;
RP   HIS-198; THR-202; CYS-282; GLY-282; HIS-282 AND CYS-297, AND
RP   CHARACTERIZATION OF VARIANT CMS23 GLN-247.
RX   PubMed=29031613; DOI=10.1016/j.bbabio.2017.10.002;
RA   Majd H., King M.S., Smith A.C., Kunji E.R.S.;
RT   "Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1
RT   lead to impaired citrate export required for lipid, dolichol, ubiquinone
RT   and sterol synthesis.";
RL   Biochim. Biophys. Acta 1859:1-7(2018).
RN   [12]
RP   FUNCTION, TRANSPORTER ACTIVITY, VARIANTS D2L2AD THR-28; ASN-40; LYS-47;
RP   ASP-93; TRP-193 AND ARG-262, AND CHARACTERIZATION OF VARIANTS D2L2AD
RP   THR-28; ASN-40; LYS-47; ASP-93; TRP-193; 256-TYR--ASP-311 DEL AND ARG-262.
RX   PubMed=29238895; DOI=10.1007/s10545-017-0106-7;
RA   Pop A., Williams M., Struys E.A., Monne M., Jansen E.E.W., De Grassi A.,
RA   Kanhai W.A., Scarcia P., Ojeda M.R.F., Porcelli V., van Dooren S.J.M.,
RA   Lennertz P., Nota B., Abdenur J.E., Coman D., Das A.M., El-Gharbawy A.,
RA   Nuoffer J.M., Polic B., Santer R., Weinhold N., Zuccarelli B., Palmieri F.,
RA   Palmieri L., Salomons G.S.;
RT   "An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional
RT   analysis of CIC variants.";
RL   J. Inherit. Metab. Dis. 41:169-180(2018).
RN   [13]
RP   VARIANTS D2L2AD LEU-45; GLN-144; ARG-167; TRP-193; THR-202;
RP   256-TYR--ASP-311 DEL; CYS-282; GLY-282 AND CYS-297, AND CHARACTERIZATION OF
RP   VARIANT D2L2AD 256-TYR--ASP-311 DEL.
RX   PubMed=23561848; DOI=10.1016/j.ajhg.2013.03.009;
RA   Nota B., Struys E.A., Pop A., Jansen E.E., Fernandez Ojeda M.R.,
RA   Kanhai W.A., Kranendijk M., van Dooren S.J., Bevova M.R., Sistermans E.A.,
RA   Nieuwint A.W., Barth M., Ben-Omran T., Hoffmann G.F., de Lonlay P.,
RA   McDonald M.T., Meberg A., Muntau A.C., Nuoffer J.M., Parini R., Read M.H.,
RA   Renneberg A., Santer R., Strahleck T., van Schaftingen E.,
RA   van der Knaap M.S., Jakobs C., Salomons G.S.;
RT   "Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes
RT   combined D-2- and L-2-hydroxyglutaric aciduria.";
RL   Am. J. Hum. Genet. 92:627-631(2013).
RN   [14]
RP   VARIANTS D2L2AD ASP-130 AND HIS-282.
RX   PubMed=23393310; DOI=10.1136/jmedgenet-2012-101485;
RA   Edvardson S., Porcelli V., Jalas C., Soiferman D., Kellner Y., Shaag A.,
RA   Korman S.H., Pierri C.L., Scarcia P., Fraenkel N.D., Segel R.,
RA   Schechter A., Frumkin A., Pines O., Saada A., Palmieri L., Elpeleg O.;
RT   "Agenesis of corpus callosum and optic nerve hypoplasia due to mutations in
RT   SLC25A1 encoding the mitochondrial citrate transporter.";
RL   J. Med. Genet. 50:240-245(2013).
RN   [15]
RP   VARIANT D2L2AD LEU-45.
RX   PubMed=25614306; DOI=10.1007/8904_2014_378;
RA   Prasun P., Young S., Salomons G., Werneke A., Jiang Y.H., Struys E.,
RA   Paige M., Avantaggiati M.L., McDonald M.;
RT   "Expanding the clinical spectrum of mitochondrial citrate carrier (SLC25A1)
RT   deficiency: Facial dysmorphism in siblings with epileptic encephalopathy
RT   and combined D,L-2-hydroxyglutaric aciduria.";
RL   JIMD Rep. 19:111-115(2015).
RN   [16]
RP   VARIANT D2L2AD HIS-198.
RX   PubMed=27306203; DOI=10.1007/8904_2016_536;
RG   FORGE Canada Consortium;
RA   Smith A., McBride S., Marcadier J.L., Michaud J., Al-Dirbashi O.Y.,
RA   Schwartzentruber J., Beaulieu C.L., Katz S.L., Majewski J., Bulman D.E.,
RA   Geraghty M.T., Harper M.E., Chakraborty P., Lines M.A.;
RT   "Severe neonatal presentation of mitochondrial citrate carrier (SLC25A1)
RT   deficiency.";
RL   JIMD Rep. 30:73-79(2016).
RN   [17]
RP   VARIANT D2L2AD SER-238.
RX   PubMed=29226520; DOI=10.1002/ajmg.a.38574;
RA   Cohen I., Staretz-Chacham O., Wormser O., Perez Y., Saada A., Kadir R.,
RA   Birk O.S.;
RT   "A novel homozygous SLC25A1 mutation with impaired mitochondrial complex V:
RT   Possible phenotypic expansion.";
RL   Am. J. Med. Genet. A 176:330-336(2018).
CC   -!- FUNCTION: Mitochondrial electroneutral antiporter that exports citrate
CC       from the mitochondria into the cytosol in exchange for malate
CC       (PubMed:29031613, PubMed:29238895). Also able to mediate the exchange
CC       of citrate for isocitrate, phosphoenolpyruvate, cis-aconitate and to a
CC       lesser extend cis-aconitate, maleate and succinate (PubMed:29031613).
CC       In the cytoplasm citrate is important in the regulation of glycolysis
CC       through a feedback mechanism and in the production of acetyl-CoA which
CC       is needed for the synthesis of fatty acids, sterols, prostaglandins,
CC       dolichol and coenzyme Q (CoQ). Required for proper neuromuscular
CC       junction formation (Probable). {ECO:0000269|PubMed:29031613,
CC       ECO:0000269|PubMed:29238895, ECO:0000305|PubMed:26870663}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-malate(in) + citrate(out) = (S)-malate(out) + citrate(in);
CC         Xref=Rhea:RHEA:72483, ChEBI:CHEBI:15589, ChEBI:CHEBI:16947;
CC         Evidence={ECO:0000269|PubMed:29031613, ECO:0000305|PubMed:29238895};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=citrate(out) + D-threo-isocitrate(in) = citrate(in) + D-threo-
CC         isocitrate(out); Xref=Rhea:RHEA:72471, ChEBI:CHEBI:15562,
CC         ChEBI:CHEBI:16947; Evidence={ECO:0000269|PubMed:29031613};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=citrate(out) + succinate(in) = citrate(in) + succinate(out);
CC         Xref=Rhea:RHEA:28835, ChEBI:CHEBI:16947, ChEBI:CHEBI:30031;
CC         Evidence={ECO:0000269|PubMed:29031613};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cis-aconitate(in) + citrate(out) = cis-aconitate(out) +
CC         citrate(in); Xref=Rhea:RHEA:72475, ChEBI:CHEBI:16383,
CC         ChEBI:CHEBI:16947; Evidence={ECO:0000269|PubMed:29031613};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=citrate(out) + trans-aconitate(in) = citrate(in) + trans-
CC         aconitate(out); Xref=Rhea:RHEA:72479, ChEBI:CHEBI:15708,
CC         ChEBI:CHEBI:16947; Evidence={ECO:0000269|PubMed:29031613};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=citrate(out) + phosphoenolpyruvate(in) = citrate(in) +
CC         phosphoenolpyruvate(out); Xref=Rhea:RHEA:72487, ChEBI:CHEBI:16947,
CC         ChEBI:CHEBI:58702; Evidence={ECO:0000269|PubMed:29031613};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=citrate(out) + maleate(in) = citrate(in) + maleate(out);
CC         Xref=Rhea:RHEA:72491, ChEBI:CHEBI:16947, ChEBI:CHEBI:30780;
CC         Evidence={ECO:0000269|PubMed:29031613};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=7.5 uM for citrate {ECO:0000269|PubMed:29031613};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:Q8JZU2}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- PTM: Possesses a short cleavable presequence, which, however, is found
CC       to be dispensable both for targeting to mitochondria and insertion into
CC       the inner membrane. However, the presequence is required to keep
CC       SLC25A1 in a soluble state and thus in an import-competent state.
CC       Mature SLC25A1 lacking the presequence is prone to aggregation.
CC       {ECO:0000250|UniProtKB:P32089}.
CC   -!- DISEASE: Combined D-2- and L-2-hydroxyglutaric aciduria (D2L2AD)
CC       [MIM:615182]: An autosomal recessive neurometabolic disorder
CC       characterized by neonatal-onset encephalopathy with severe muscular
CC       weakness, intractable seizures, respiratory distress, and lack of
CC       psychomotor development resulting in early death. Brain imaging shows
CC       abnormalities including enlarged ventricles, delayed myelination, and
CC       germinal layer cysts. {ECO:0000269|PubMed:23393310,
CC       ECO:0000269|PubMed:23561848, ECO:0000269|PubMed:25614306,
CC       ECO:0000269|PubMed:27306203, ECO:0000269|PubMed:29031613,
CC       ECO:0000269|PubMed:29226520, ECO:0000269|PubMed:29238895}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Myasthenic syndrome, congenital, 23, presynaptic (CMS23)
CC       [MIM:618197]: A form of congenital myasthenic syndrome, a group of
CC       disorders characterized by failure of neuromuscular transmission,
CC       including pre-synaptic, synaptic, and post-synaptic disorders that are
CC       not of autoimmune origin. Clinical features include easy fatigability
CC       and muscle weakness. CMS23 inheritance is autosomal recessive.
CC       {ECO:0000269|PubMed:26870663, ECO:0000269|PubMed:29031613}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC       {ECO:0000305}.
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DR   EMBL; U25147; AAB08515.1; -; mRNA.
DR   EMBL; L76134; AAL40091.1; -; Genomic_DNA.
DR   EMBL; L75823; AAL40090.1; -; mRNA.
DR   EMBL; AK292313; BAF85002.1; -; mRNA.
DR   EMBL; BC004980; AAH04980.1; -; mRNA.
DR   EMBL; BC008061; AAH08061.1; -; mRNA.
DR   CCDS; CCDS13758.1; -.
DR   PIR; G01789; G01789.
DR   RefSeq; NP_005975.1; NM_005984.4.
DR   AlphaFoldDB; P53007; -.
DR   SMR; P53007; -.
DR   BioGRID; 112464; 263.
DR   IntAct; P53007; 104.
DR   MINT; P53007; -.
DR   STRING; 9606.ENSP00000215882; -.
DR   DrugBank; DB09154; Sodium citrate.
DR   GuidetoPHARMACOLOGY; 1051; -.
DR   TCDB; 2.A.29.7.2; the mitochondrial carrier (mc) family.
DR   GlyGen; P53007; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P53007; -.
DR   PhosphoSitePlus; P53007; -.
DR   SwissPalm; P53007; -.
DR   BioMuta; SLC25A1; -.
DR   DMDM; 20141931; -.
DR   CPTAC; CPTAC-586; -.
DR   CPTAC; CPTAC-587; -.
DR   EPD; P53007; -.
DR   jPOST; P53007; -.
DR   MassIVE; P53007; -.
DR   MaxQB; P53007; -.
DR   PaxDb; 9606-ENSP00000215882; -.
DR   PeptideAtlas; P53007; -.
DR   ProteomicsDB; 56567; -.
DR   Pumba; P53007; -.
DR   TopDownProteomics; P53007; -.
DR   Antibodypedia; 22859; 180 antibodies from 23 providers.
DR   DNASU; 6576; -.
DR   Ensembl; ENST00000215882.10; ENSP00000215882.5; ENSG00000100075.10.
DR   GeneID; 6576; -.
DR   KEGG; hsa:6576; -.
DR   MANE-Select; ENST00000215882.10; ENSP00000215882.5; NM_005984.5; NP_005975.1.
DR   UCSC; uc002zoz.6; human.
DR   AGR; HGNC:10979; -.
DR   CTD; 6576; -.
DR   DisGeNET; 6576; -.
DR   GeneCards; SLC25A1; -.
DR   GeneReviews; SLC25A1; -.
DR   HGNC; HGNC:10979; SLC25A1.
DR   HPA; ENSG00000100075; Tissue enhanced (liver).
DR   MalaCards; SLC25A1; -.
DR   MIM; 190315; gene.
DR   MIM; 615182; phenotype.
DR   MIM; 618197; phenotype.
DR   neXtProt; NX_P53007; -.
DR   OpenTargets; ENSG00000100075; -.
DR   Orphanet; 356978; D,L-2-hydroxyglutaric aciduria.
DR   Orphanet; 98914; Presynaptic congenital myasthenic syndromes.
DR   PharmGKB; PA35855; -.
DR   VEuPathDB; HostDB:ENSG00000100075; -.
DR   eggNOG; KOG0756; Eukaryota.
DR   GeneTree; ENSGT00550000074856; -.
DR   HOGENOM; CLU_015166_5_1_1; -.
DR   InParanoid; P53007; -.
DR   OMA; AWYAGCT; -.
DR   OrthoDB; 5473154at2759; -.
DR   PhylomeDB; P53007; -.
DR   TreeFam; TF105786; -.
DR   PathwayCommons; P53007; -.
DR   Reactome; R-HSA-70263; Gluconeogenesis.
DR   Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis.
DR   SignaLink; P53007; -.
DR   SIGNOR; P53007; -.
DR   BioGRID-ORCS; 6576; 81 hits in 1160 CRISPR screens.
DR   ChiTaRS; SLC25A1; human.
DR   GeneWiki; SLC25A1; -.
DR   GenomeRNAi; 6576; -.
DR   Pharos; P53007; Tbio.
DR   PRO; PR:P53007; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; P53007; Protein.
DR   Bgee; ENSG00000100075; Expressed in endometrium epithelium and 194 other cell types or tissues.
DR   ExpressionAtlas; P53007; baseline and differential.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR   GO; GO:0071913; F:citrate secondary active transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0015137; F:citrate transmembrane transporter activity; TAS:UniProtKB.
DR   GO; GO:0015142; F:tricarboxylic acid transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0046949; P:fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR   GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR   GO; GO:0006843; P:mitochondrial citrate transmembrane transport; IDA:UniProtKB.
DR   Gene3D; 1.50.40.10; Mitochondrial carrier domain; 1.
DR   InterPro; IPR002067; Mit_carrier.
DR   InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR   InterPro; IPR023395; Mt_carrier_dom_sf.
DR   InterPro; IPR049563; TXTP-like.
DR   PANTHER; PTHR45788; SUCCINATE/FUMARATE MITOCHONDRIAL TRANSPORTER-RELATED; 1.
DR   PANTHER; PTHR45788:SF4; TRICARBOXYLATE TRANSPORT PROTEIN, MITOCHONDRIAL; 1.
DR   Pfam; PF00153; Mito_carr; 3.
DR   PRINTS; PR00926; MITOCARRIER.
DR   SUPFAM; SSF103506; Mitochondrial carrier; 1.
DR   PROSITE; PS50920; SOLCAR; 3.
DR   Genevisible; P53007; HS.
PE   1: Evidence at protein level;
KW   Antiport; Congenital myasthenic syndrome; Disease variant; Membrane;
KW   Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW   Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT   PROPEP          1..13
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250|UniProtKB:P32089"
FT                   /id="PRO_0000456575"
FT   CHAIN           14..311
FT                   /note="Tricarboxylate transport protein, mitochondrial"
FT                   /id="PRO_0000019262"
FT   TRANSMEM        29..46
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        86..105
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        129..143
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        183..202
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        224..241
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        278..297
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   REPEAT          23..111
FT                   /note="Solcar 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT   REPEAT          122..208
FT                   /note="Solcar 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT   REPEAT          218..303
FT                   /note="Solcar 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT   MOD_RES         156
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         28
FT                   /note="A -> T (in D2L2AD; uncertain significance; very mild
FT                   decrease of citrate transport rates)"
FT                   /evidence="ECO:0000269|PubMed:29238895"
FT                   /id="VAR_081661"
FT   VARIANT         40
FT                   /note="I -> N (in D2L2AD; reduced rates of citrate
FT                   transport)"
FT                   /evidence="ECO:0000269|PubMed:29238895"
FT                   /id="VAR_081662"
FT   VARIANT         45
FT                   /note="P -> L (in D2L2AD; severely reduced rates of citrate
FT                   transport)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:25614306, ECO:0000269|PubMed:29031613"
FT                   /id="VAR_069490"
FT   VARIANT         47
FT                   /note="E -> K (in D2L2AD; severely reduced rates of citrate
FT                   transport; dbSNP:rs1555923307)"
FT                   /evidence="ECO:0000269|PubMed:29238895"
FT                   /id="VAR_081663"
FT   VARIANT         93
FT                   /note="G -> D (in D2L2AD; severely reduced rates of citrate
FT                   transport)"
FT                   /evidence="ECO:0000269|PubMed:29238895"
FT                   /id="VAR_081664"
FT   VARIANT         130
FT                   /note="G -> D (in D2L2AD; severely reduced rates of citrate
FT                   transport; dbSNP:rs368647424)"
FT                   /evidence="ECO:0000269|PubMed:23393310,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_081665"
FT   VARIANT         144
FT                   /note="E -> Q (in D2L2AD; abolishes citrate transport)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_069491"
FT   VARIANT         167
FT                   /note="G -> R (in D2L2AD)"
FT                   /evidence="ECO:0000269|PubMed:23561848"
FT                   /id="VAR_069492"
FT   VARIANT         193
FT                   /note="S -> W (in D2L2AD; reduced rates of citrate
FT                   transport; dbSNP:rs781925968)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:29031613, ECO:0000269|PubMed:29238895"
FT                   /id="VAR_069493"
FT   VARIANT         198
FT                   /note="R -> H (in D2L2AD; severely reduced rates of citrate
FT                   transport; dbSNP:rs1331417017)"
FT                   /evidence="ECO:0000269|PubMed:27306203,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_077511"
FT   VARIANT         202
FT                   /note="M -> T (in D2L2AD; reduced rates of citrate
FT                   transport; dbSNP:rs782335811)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_069494"
FT   VARIANT         238
FT                   /note="N -> S (in D2L2AD; disease phenotype may include
FT                   decreased activity of mitochondrial respiratory chain
FT                   complex V)"
FT                   /evidence="ECO:0000269|PubMed:29226520"
FT                   /id="VAR_081666"
FT   VARIANT         247
FT                   /note="R -> Q (in CMS23; reduced rates of citrate
FT                   transport; dbSNP:rs781908532)"
FT                   /evidence="ECO:0000269|PubMed:26870663,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_081667"
FT   VARIANT         256..311
FT                   /note="Missing (in D2L2AD; no protein detected by Western
FT                   blot in patient fibroblasts; severely reduced rates of
FT                   citrate transport)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:29238895"
FT                   /id="VAR_081668"
FT   VARIANT         262
FT                   /note="C -> R (in D2L2AD; reduced rates of citrate
FT                   transport)"
FT                   /evidence="ECO:0000269|PubMed:29238895"
FT                   /id="VAR_081669"
FT   VARIANT         282
FT                   /note="R -> C (in D2L2AD; abolishes citrate transport;
FT                   dbSNP:rs431905509)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_069495"
FT   VARIANT         282
FT                   /note="R -> G (in D2L2AD; abolishes citrate transport;
FT                   dbSNP:rs431905509)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_069496"
FT   VARIANT         282
FT                   /note="R -> H (in D2L2AD; abolishes citrate transport;
FT                   dbSNP:rs431905510)"
FT                   /evidence="ECO:0000269|PubMed:23393310,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_081670"
FT   VARIANT         297
FT                   /note="Y -> C (in D2L2AD; reduced rates of citrate
FT                   transport)"
FT                   /evidence="ECO:0000269|PubMed:23561848,
FT                   ECO:0000269|PubMed:29031613"
FT                   /id="VAR_069497"
FT   CONFLICT        26
FT                   /note="G -> E (in Ref. 1; AAB08515)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   311 AA;  34013 MW;  F1341629924953D6 CRC64;
     MPAPRAPRAL AAAAPASGKA KLTHPGKAIL AGGLAGGIEI CITFPTEYVK TQLQLDERSH
     PPRYRGIGDC VRQTVRSHGV LGLYRGLSSL LYGSIPKAAV RFGMFEFLSN HMRDAQGRLD
     STRGLLCGLG AGVAEAVVVV CPMETIKVKF IHDQTSPNPK YRGFFHGVRE IVREQGLKGT
     YQGLTATVLK QGSNQAIRFF VMTSLRNWYR GDNPNKPMNP LITGVFGAIA GAASVFGNTP
     LDVIKTRMQG LEAHKYRNTW DCGLQILKKE GLKAFYKGTV PRLGRVCLDV AIVFVIYDEV
     VKLLNKVWKT D
//