ID ODC_HUMAN Reviewed; 299 AA. AC Q9BQT8; A8K0L0; G3V4L5; Q3MJ99; DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 24-JAN-2024, entry version 166. DE RecName: Full=Mitochondrial 2-oxodicarboxylate carrier; DE Short=ODC {ECO:0000303|PubMed:11083877}; DE AltName: Full=Mitochondrial 2-oxoadipate carrier {ECO:0000303|PubMed:11083877}; DE AltName: Full=Solute carrier family 25 member 21; GN Name=SLC25A21; Synonyms=ODC; 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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP TRANSPORT ACTIVITY. RC TISSUE=Liver; RX PubMed=11083877; DOI=10.1074/jbc.m009607200; RA Fiermonte G., Dolce V., Palmieri L., Ventura M., Runswick M.J., RA Palmieri F., Walker J.E.; RT "Identification of the human mitochondrial oxodicarboxylate carrier. RT Bacterial expression, reconstitution, functional characterization, tissue RT distribution and chromosomal location."; RL J. Biol. Chem. 276:8225-8230(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Cerebellum; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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=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 [6] RP VARIANT MTDPS18 ARG-232, INVOLVEMENT IN MTDPS18, CHARACTERIZATION OF RP VARIANT MTDPS18 ARG-232, AND FUNCTION. RX PubMed=29517768; DOI=10.1038/gim.2017.251; RA Boczonadi V., King M.S., Smith A.C., Olahova M., Bansagi B., Roos A., RA Eyassu F., Borchers C., Ramesh V., Lochmueller H., Polvikoski T., RA Whittaker R.G., Pyle A., Griffin H., Taylor R.W., Chinnery P.F., RA Robinson A.J., Kunji E.R.S., Horvath R.; RT "Mitochondrial oxodicarboxylate carrier deficiency is associated with RT mitochondrial DNA depletion and spinal muscular atrophy-like disease."; RL Genet. Med. 20:1224-1235(2018). CC -!- FUNCTION: Transports dicarboxylates across the inner membranes of CC mitochondria by a counter-exchange mechanism (PubMed:11083877). Can CC transport 2-oxoadipate (2-oxohexanedioate), 2-oxoglutarate, adipate CC (hexanedioate), glutarate, and to a lesser extent, pimelate CC (heptanedioate), 2-oxopimelate (2-oxoheptanedioate), 2-aminoadipate (2- CC aminohexanedioate), oxaloacetate, and citrate (PubMed:11083877). Plays CC a central role in catabolism of lysine, hydroxylysine, and tryptophan, CC by transporting common metabolite intermediates (such as 2-oxoadipate) CC into the mitochondria, where it is converted into acetyl-CoA and can CC enter the citric acid (TCA) cycle (Probable). CC {ECO:0000269|PubMed:11083877, ECO:0000305|PubMed:11083877, CC ECO:0000305|PubMed:29517768}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoadipate(in) + 2-oxoglutarate(out) = 2-oxoadipate(out) + CC 2-oxoglutarate(in); Xref=Rhea:RHEA:71739, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:57499; Evidence={ECO:0000269|PubMed:11083877}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate(out) + hexanedioate(in) = 2-oxoglutarate(in) + CC hexanedioate(out); Xref=Rhea:RHEA:71743, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:17128; Evidence={ECO:0000269|PubMed:11083877}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate(out) + L-2-aminoadipate(in) = 2- CC oxoglutarate(in) + L-2-aminoadipate(out); Xref=Rhea:RHEA:71747, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:58672; CC Evidence={ECO:0000269|PubMed:11083877}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate(out) + glutarate(in) = 2-oxoglutarate(in) + CC glutarate(out); Xref=Rhea:RHEA:71751, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:30921; Evidence={ECO:0000269|PubMed:11083877}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate(out) + 2-oxoheptanedioate(in) = 2- CC oxoglutarate(in) + 2-oxoheptanedioate(out); Xref=Rhea:RHEA:71755, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:72701; CC Evidence={ECO:0000269|PubMed:11083877}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate(out) + heptanedioate(in) = 2-oxoglutarate(in) + CC heptanedioate(out); Xref=Rhea:RHEA:71759, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:36165; Evidence={ECO:0000269|PubMed:11083877}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate(out) + citrate(in) = 2-oxoglutarate(in) + CC citrate(out); Xref=Rhea:RHEA:71763, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16947; Evidence={ECO:0000269|PubMed:11083877}; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane CC protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BQT8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BQT8-2; Sequence=VSP_046690; CC -!- TISSUE SPECIFICITY: Expressed in placenta, gall bladder and colon. CC {ECO:0000269|PubMed:11083877}. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 18 (MTDPS18) CC [MIM:618811]: An autosomal recessive mitochondrial disorder CC characterized by early-onset progressive weakness and atrophy of the CC distal limb muscles, loss of ambulation, and atrophy of the intrinsic CC hand muscles with clawed hands. Additional features include scoliosis, CC hypo- or hyperreflexia, and decreased pulmonary vital capacity. CC Examination of skeletal muscle shows mitochondrial respiratory chain CC deficiencies involving complexes I and IV, associated with mtDNA CC depletion. {ECO:0000269|PubMed:29517768}. Note=The disease may be CC caused 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; AJ278148; CAC27562.1; -; mRNA. DR EMBL; AK289575; BAF82264.1; -; mRNA. DR EMBL; AL079303; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL079304; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL121775; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL162464; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC101521; AAI01522.1; -; mRNA. DR EMBL; BC113365; AAI13366.1; -; mRNA. DR CCDS; CCDS55913.1; -. [Q9BQT8-2] DR CCDS; CCDS9663.1; -. [Q9BQT8-1] DR RefSeq; NP_001164641.1; NM_001171170.1. [Q9BQT8-2] DR RefSeq; NP_085134.1; NM_030631.3. [Q9BQT8-1] DR AlphaFoldDB; Q9BQT8; -. DR SMR; Q9BQT8; -. DR BioGRID; 124629; 19. DR IntAct; Q9BQT8; 8. DR STRING; 9606.ENSP00000329452; -. DR BindingDB; Q9BQT8; -. DR ChEMBL; CHEMBL4680040; -. DR DrugBank; DB09154; Sodium citrate. DR TCDB; 2.A.29.2.4; the mitochondrial carrier (mc) family. DR iPTMnet; Q9BQT8; -. DR PhosphoSitePlus; Q9BQT8; -. DR BioMuta; SLC25A21; -. DR EPD; Q9BQT8; -. DR jPOST; Q9BQT8; -. DR MassIVE; Q9BQT8; -. DR MaxQB; Q9BQT8; -. DR PaxDb; 9606-ENSP00000329452; -. DR PeptideAtlas; Q9BQT8; -. DR ProteomicsDB; 33264; -. DR ProteomicsDB; 78721; -. [Q9BQT8-1] DR Pumba; Q9BQT8; -. DR Antibodypedia; 32; 175 antibodies from 28 providers. DR DNASU; 89874; -. DR Ensembl; ENST00000331299.6; ENSP00000329452.5; ENSG00000183032.12. [Q9BQT8-1] DR Ensembl; ENST00000555449.5; ENSP00000451873.1; ENSG00000183032.12. [Q9BQT8-2] DR GeneID; 89874; -. DR KEGG; hsa:89874; -. DR MANE-Select; ENST00000331299.6; ENSP00000329452.5; NM_030631.4; NP_085134.1. DR UCSC; uc001wtz.3; human. [Q9BQT8-1] DR AGR; HGNC:14411; -. DR CTD; 89874; -. DR DisGeNET; 89874; -. DR GeneCards; SLC25A21; -. DR HGNC; HGNC:14411; SLC25A21. DR HPA; ENSG00000183032; Tissue enhanced (bone). DR MalaCards; SLC25A21; -. DR MIM; 607571; gene. DR MIM; 618811; phenotype. DR neXtProt; NX_Q9BQT8; -. DR OpenTargets; ENSG00000183032; -. DR PharmGKB; PA37880; -. DR VEuPathDB; HostDB:ENSG00000183032; -. DR eggNOG; KOG0754; Eukaryota. DR GeneTree; ENSGT00730000111119; -. DR HOGENOM; CLU_015166_5_2_1; -. DR InParanoid; Q9BQT8; -. DR OMA; LPFQYQF; -. DR OrthoDB; 314985at2759; -. DR PhylomeDB; Q9BQT8; -. DR TreeFam; TF314035; -. DR PathwayCommons; Q9BQT8; -. DR Reactome; R-HSA-71064; Lysine catabolism. DR SignaLink; Q9BQT8; -. DR BioGRID-ORCS; 89874; 8 hits in 1172 CRISPR screens. DR ChiTaRS; SLC25A21; human. DR GeneWiki; SLC25A21; -. DR GenomeRNAi; 89874; -. DR Pharos; Q9BQT8; Tchem. DR PRO; PR:Q9BQT8; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9BQT8; Protein. DR Bgee; ENSG00000183032; Expressed in primordial germ cell in gonad and 98 other cell types or tissues. DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:FlyBase. DR GO; GO:0015139; F:alpha-ketoglutarate transmembrane transporter activity; IDA:FlyBase. DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW. DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW. DR GO; GO:0006554; P:lysine catabolic process; TAS:Reactome. DR GO; GO:1990550; P:mitochondrial alpha-ketoglutarate transmembrane transport; IMP:FlyBase. DR Gene3D; 1.50.40.10; Mitochondrial carrier domain; 2. DR InterPro; IPR002067; Mit_carrier. DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier. DR InterPro; IPR023395; Mt_carrier_dom_sf. DR PANTHER; PTHR46356; MITOCHONDRIAL 2-OXODICARBOXYLATE CARRIER; 1. DR PANTHER; PTHR46356:SF1; MITOCHONDRIAL 2-OXODICARBOXYLATE CARRIER; 1. DR Pfam; PF00153; Mito_carr; 3. DR PRINTS; PR00926; MITOCARRIER. DR SUPFAM; SSF103506; Mitochondrial carrier; 1. DR PROSITE; PS50920; SOLCAR; 3. DR Genevisible; Q9BQT8; HS. PE 1: Evidence at protein level; KW Alternative splicing; Antiport; Disease variant; Lipid transport; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease; KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..299 FT /note="Mitochondrial 2-oxodicarboxylate carrier" FT /id="PRO_0000090644" FT TRANSMEM 17..37 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TRANSMEM 70..89 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TRANSMEM 113..133 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TRANSMEM 167..187 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TRANSMEM 205..225 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TRANSMEM 277..297 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT REPEAT 11..100 FT /note="Solcar 1" FT REPEAT 107..196 FT /note="Solcar 2" FT REPEAT 205..294 FT /note="Solcar 3" FT VAR_SEQ 299 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046690" FT VARIANT 232 FT /note="K -> R (in MTDPS18; loss of 2-oxoglutarate FT transporter activity; dbSNP:rs1389068504)" FT /evidence="ECO:0000269|PubMed:29517768" FT /id="VAR_083870" FT VARIANT 299 FT /note="W -> C (in dbSNP:rs17104991)" FT /id="VAR_050131" SQ SEQUENCE 299 AA; 33303 MW; 69A259400328AE19 CRC64; MSAKPEVSLV REASRQIVAG GSAGLVEICL MHPLDVVKTR FQIQRCATDP NSYKSLVDSF RMIFQMEGLF GFYKGILPPI LAETPKRAVK FFTFEQYKKL LGYVSLSPAL TFAIAGLGSG LTEAIVVNPF EVVKVGLQAN RNTFAEQPST VGYARQIIKK EGWGLQGLNK GLTATLGRHG VFNMVYFGFY YNVKNMIPVN KDPILEFWRK FGIGLLSGTI ASVINIPFDV AKSRIQGPQP VPGEIKYRTC FKTMATVYQE EGILALYKGL LPKIMRLGPG GAVMLLVYEY TYSWLQENW //