ODC_HUMAN
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 03-AUG-2022, entry version 158.
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}.
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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; 17.
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; Q9BQT8; -.
DR PeptideAtlas; Q9BQT8; -.
DR PRIDE; Q9BQT8; -.
DR ProteomicsDB; 33264; -.
DR ProteomicsDB; 78721; -. [Q9BQT8-1]
DR Antibodypedia; 32; 161 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 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; MLLVFDY; -.
DR OrthoDB; 1236425at2759; -.
DR PhylomeDB; Q9BQT8; -.
DR TreeFam; TF314035; -.
DR PathwayCommons; Q9BQT8; -.
DR Reactome; R-HSA-71064; Lysine catabolism.
DR SignaLink; Q9BQT8; -.
DR BioGRID-ORCS; 89874; 6 hits in 1081 CRISPR screens.
DR ChiTaRS; SLC25A21; human.
DR GeneWiki; SLC25A21; -.
DR GenomeRNAi; 89874; -.
DR Pharos; Q9BQT8; Tbio.
DR PRO; PR:Q9BQT8; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9BQT8; protein.
DR Bgee; ENSG00000183032; Expressed in stromal cell of endometrium and 96 other tissues.
DR Genevisible; Q9BQT8; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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; -; 2.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
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
