DIC_HUMAN
ID DIC_HUMAN Reviewed; 287 AA.
AC Q9UBX3; Q542Z3; Q96BA1; Q96IP1;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 11-FEB-2002, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Mitochondrial dicarboxylate carrier {ECO:0000303|PubMed:10585886};
DE Short=DIC;
DE AltName: Full=Solute carrier family 25 member 10;
GN Name=SLC25A10; Synonyms=DIC;
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 / MRNA] (ISOFORM 1), AND TISSUE
RP SPECIFICITY.
RX PubMed=10585886; DOI=10.1042/bj3440953;
RA Fiermonte G., Dolce V., Arrigoni R., Runswick M.J., Walker J.E.,
RA Palmieri F.;
RT "Organization and sequence of the gene for the human mitochondrial
RT dicarboxylate carrier: evolution of the carrier family.";
RL Biochem. J. 344:953-960(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thyroid;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin, and Uterus;
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 INVOLVEMENT IN MTDPS19, VARIANT MTDPS19 102-LYS--SER-287 DEL,
RP CHARACTERIZATION OF VARIANT MTDPS19 102-LYS--SER-287 DEL, FUNCTION, AND
RP TRANSPORT ACTIVITY.
RX PubMed=29211846; DOI=10.1093/hmg/ddx419;
RA Punzi G., Porcelli V., Ruggiu M., Hossain M.F., Menga A., Scarcia P.,
RA Castegna A., Gorgoglione R., Pierri C.L., Laera L., Lasorsa F.M.,
RA Paradies E., Pisano I., Marobbio C.M.T., Lamantea E., Ghezzi D.,
RA Tiranti V., Giannattasio S., Donati M.A., Guerrini R., Palmieri L.,
RA Palmieri F., De Grassi A.;
RT "SLC25A10 biallelic mutations in intractable epileptic encephalopathy with
RT complex I deficiency.";
RL Hum. Mol. Genet. 27:499-504(2018).
CC -!- FUNCTION: Catalyzes the electroneutral exchange or flux of
CC physiologically important metabolites such as dicarboxylates (malonate,
CC malate, succinate), inorganic sulfur-containing anions, and phosphate,
CC across mitochondrial inner membrane (PubMed:29211846). Plays an
CC important role in gluconeogenesis, fatty acid metabolism, urea
CC synthesis, and sulfur metabolism, particularly in liver, by supplying
CC the substrates for the different metabolic processes. Regulates fatty
CC acid release from adipocytes, and contributes to systemic insulin
CC sensitivity (By similarity). {ECO:0000250|UniProtKB:Q9QZD8,
CC ECO:0000269|PubMed:29211846}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate(in) + phosphate(out) = (S)-malate(out) +
CC phosphate(in); Xref=Rhea:RHEA:71607, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:43474; Evidence={ECO:0000305|PubMed:29211846};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate(in) + malonate(out) = (S)-malate(out) +
CC malonate(in); Xref=Rhea:RHEA:71611, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:15792; Evidence={ECO:0000250|UniProtKB:O89035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate(in) + succinate(out) = (S)-malate(out) +
CC succinate(in); Xref=Rhea:RHEA:29327, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:30031; Evidence={ECO:0000250|UniProtKB:O89035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate(in) + sulfate(out) = (S)-malate(out) + sulfate(in);
CC Xref=Rhea:RHEA:71615, ChEBI:CHEBI:15589, ChEBI:CHEBI:16189;
CC Evidence={ECO:0000250|UniProtKB:O89035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=malonate(out) + phosphate(in) = malonate(in) + phosphate(out);
CC Xref=Rhea:RHEA:71623, ChEBI:CHEBI:15792, ChEBI:CHEBI:43474;
CC Evidence={ECO:0000250|UniProtKB:O89035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=phosphate(in) + succinate(out) = phosphate(out) +
CC succinate(in); Xref=Rhea:RHEA:71627, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:43474; Evidence={ECO:0000250|UniProtKB:O89035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=phosphate(in) + sulfate(out) = phosphate(out) + sulfate(in);
CC Xref=Rhea:RHEA:71631, ChEBI:CHEBI:16189, ChEBI:CHEBI:43474;
CC Evidence={ECO:0000250|UniProtKB:O89035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=malonate(out) + succinate(in) = malonate(in) + succinate(out);
CC Xref=Rhea:RHEA:71667, ChEBI:CHEBI:15792, ChEBI:CHEBI:30031;
CC Evidence={ECO:0000250|UniProtKB:Q9QZD8};
CC -!- INTERACTION:
CC Q9UBX3; Q6A162: KRT40; NbExp=3; IntAct=EBI-750394, EBI-10171697;
CC Q9UBX3; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-750394, EBI-10171774;
CC Q9UBX3; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-750394, EBI-10172511;
CC Q9UBX3; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-750394, EBI-3958099;
CC Q9UBX3; Q99750: MDFI; NbExp=7; IntAct=EBI-750394, EBI-724076;
CC Q9UBX3; Q7Z3S9: NOTCH2NLA; NbExp=4; IntAct=EBI-750394, EBI-945833;
CC Q9UBX3-2; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-12056597, EBI-3958099;
CC Q9UBX3-2; Q99750: MDFI; NbExp=3; IntAct=EBI-12056597, EBI-724076;
CC Q9UBX3-2; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-12056597, EBI-1210429;
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=Q9UBX3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UBX3-2; Sequence=VSP_003267;
CC -!- TISSUE SPECIFICITY: Present in high amounts in liver and kidney, and at
CC lower levels in all the other tissues analyzed.
CC {ECO:0000269|PubMed:10585886}.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 19 (MTDPS19)
CC [MIM:618972]: An autosomal recessive mitochondrial disorder
CC characterized by progressive and severe epileptic encephalopathy,
CC hypotonia, poor spontaneous movements evolving to spastic quadriparesis
CC and dyskinesias, and respiratory complex I deficiency and mitochondrial
CC DNA depletion in skeletal muscle. {ECO:0000269|PubMed:29211846}.
CC Note=The disease may be caused by variants affecting the gene
CC 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; AJ131612; CAB60007.1; -; Genomic_DNA.
DR EMBL; AJ131613; CAB59892.1; -; mRNA.
DR EMBL; AK075249; BAC11497.1; -; mRNA.
DR EMBL; CH471099; EAW89682.1; -; Genomic_DNA.
DR EMBL; BC007355; AAH07355.1; -; mRNA.
DR EMBL; BC015797; AAH15797.1; -; mRNA.
DR CCDS; CCDS11786.1; -. [Q9UBX3-1]
DR CCDS; CCDS59301.1; -. [Q9UBX3-2]
DR RefSeq; NP_001257817.1; NM_001270888.1. [Q9UBX3-2]
DR RefSeq; NP_001257882.1; NM_001270953.1.
DR RefSeq; NP_036272.2; NM_012140.4. [Q9UBX3-1]
DR AlphaFoldDB; Q9UBX3; -.
DR SMR; Q9UBX3; -.
DR BioGRID; 107850; 168.
DR IntAct; Q9UBX3; 56.
DR MINT; Q9UBX3; -.
DR STRING; 9606.ENSP00000461324; -.
DR DrugBank; DB00139; Succinic acid.
DR TCDB; 2.A.29.2.7; the mitochondrial carrier (mc) family.
DR iPTMnet; Q9UBX3; -.
DR PhosphoSitePlus; Q9UBX3; -.
DR SwissPalm; Q9UBX3; -.
DR BioMuta; SLC25A10; -.
DR DMDM; 20137671; -.
DR EPD; Q9UBX3; -.
DR jPOST; Q9UBX3; -.
DR MassIVE; Q9UBX3; -.
DR MaxQB; Q9UBX3; -.
DR PaxDb; Q9UBX3; -.
DR PeptideAtlas; Q9UBX3; -.
DR PRIDE; Q9UBX3; -.
DR ProteomicsDB; 84091; -. [Q9UBX3-1]
DR ProteomicsDB; 84092; -. [Q9UBX3-2]
DR Antibodypedia; 19833; 110 antibodies from 19 providers.
DR DNASU; 1468; -.
DR Ensembl; ENST00000331531.9; ENSP00000328403.5; ENSG00000183048.12. [Q9UBX3-2]
DR Ensembl; ENST00000350690.10; ENSP00000345580.5; ENSG00000183048.12. [Q9UBX3-1]
DR GeneID; 1468; -.
DR KEGG; hsa:1468; -.
DR MANE-Select; ENST00000350690.10; ENSP00000345580.5; NM_012140.5; NP_036272.2.
DR UCSC; uc002kbi.5; human. [Q9UBX3-1]
DR CTD; 1468; -.
DR DisGeNET; 1468; -.
DR GeneCards; SLC25A10; -.
DR HGNC; HGNC:10980; SLC25A10.
DR HPA; ENSG00000183048; Tissue enhanced (liver).
DR MalaCards; SLC25A10; -.
DR MIM; 606794; gene.
DR MIM; 618972; phenotype.
DR neXtProt; NX_Q9UBX3; -.
DR OpenTargets; ENSG00000183048; -.
DR PharmGKB; PA35856; -.
DR VEuPathDB; HostDB:ENSG00000183048; -.
DR eggNOG; KOG0759; Eukaryota.
DR eggNOG; KOG1715; Eukaryota.
DR GeneTree; ENSGT00940000156783; -.
DR HOGENOM; CLU_015166_14_1_1; -.
DR InParanoid; Q9UBX3; -.
DR OMA; FGAYEVG; -.
DR OrthoDB; 1053600at2759; -.
DR PhylomeDB; Q9UBX3; -.
DR TreeFam; TF312920; -.
DR PathwayCommons; Q9UBX3; -.
DR Reactome; R-HSA-1614517; Sulfide oxidation to sulfate.
DR Reactome; R-HSA-428643; Organic anion transporters.
DR Reactome; R-HSA-70263; Gluconeogenesis.
DR SignaLink; Q9UBX3; -.
DR BioGRID-ORCS; 1468; 237 hits in 1090 CRISPR screens.
DR ChiTaRS; SLC25A10; human.
DR GeneWiki; SLC25A10; -.
DR GenomeRNAi; 1468; -.
DR Pharos; Q9UBX3; Tbio.
DR PRO; PR:Q9UBX3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9UBX3; protein.
DR Bgee; ENSG00000183048; Expressed in right lobe of liver and 98 other tissues.
DR ExpressionAtlas; Q9UBX3; baseline and differential.
DR Genevisible; Q9UBX3; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0015297; F:antiporter activity; IBA:GO_Central.
DR GO; GO:0005310; F:dicarboxylic acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015140; F:malate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015131; F:oxaloacetate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015114; F:phosphate ion transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0015141; F:succinate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015116; F:sulfate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015117; F:thiosulfate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0006835; P:dicarboxylic acid transport; TAS:ProtInc.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0071423; P:malate transmembrane transport; IBA:GO_Central.
DR GO; GO:0006839; P:mitochondrial transport; IEA:InterPro.
DR GO; GO:0015729; P:oxaloacetate transport; IBA:GO_Central.
DR GO; GO:0035435; P:phosphate ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0071422; P:succinate transmembrane transport; IBA:GO_Central.
DR GO; GO:0008272; P:sulfate transport; IBA:GO_Central.
DR GO; GO:0070221; P:sulfide oxidation, using sulfide:quinone oxidoreductase; TAS:Reactome.
DR GO; GO:0015709; P:thiosulfate transport; IBA:GO_Central.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002030; Mit_uncoupling_UCP-like.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00784; MTUNCOUPLING.
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..287
FT /note="Mitochondrial dicarboxylate carrier"
FT /id="PRO_0000090609"
FT TRANSMEM 10..30
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..82
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..182
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 8..88
FT /note="Solcar 1"
FT REPEAT 101..188
FT /note="Solcar 2"
FT REPEAT 197..280
FT /note="Solcar 3"
FT VAR_SEQ 209
FT /note="A -> AAAGDEPPPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003267"
FT VARIANT 102..287
FT /note="Missing (in MTDPS19; no protein detected in patient
FT cells)"
FT /evidence="ECO:0000269|PubMed:29211846"
FT /id="VAR_084678"
FT CONFLICT 188
FT /note="L -> R (in Ref. 1; CAB60007/CAB59892)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 287 AA; 31282 MW; 32BE9920C7CD8ADF CRC64;
MAAEARVSRW YFGGLASCGA ACCTHPLDLL KVHLQTQQEV KLRMTGMALR VVRTDGILAL
YSGLSASLCR QMTYSLTRFA IYETVRDRVA KGSQGPLPFH EKVLLGSVSG LAGGFVGTPA
DLVNVRMQND VKLPQGQRRN YAHALDGLYR VAREEGLRRL FSGATMASSR GALVTVGQLS
CYDQAKQLVL STGYLSDNIF THFVASFIAG GCATFLCQPL DVLKTRLMNS KGEYQGVFHC
AVETAKLGPL AFYKGLVPAG IRLIPHTVLT FVFLEQLRKN FGIKVPS
