S2513_HUMAN
ID S2513_HUMAN Reviewed; 675 AA.
AC Q9UJS0; O14566; O14575; Q546F9; Q9NZW1; Q9UNI7;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial {ECO:0000305|PubMed:11566871};
DE AltName: Full=Calcium-binding mitochondrial carrier protein Aralar2;
DE Short=ARALAR-related gene 2 {ECO:0000303|PubMed:10642534};
DE Short=ARALAR2 {ECO:0000303|PubMed:10642534};
DE AltName: Full=Citrin {ECO:0000303|PubMed:10642534};
DE AltName: Full=Mitochondrial aspartate glutamate carrier 2;
DE AltName: Full=Solute carrier family 25 member 13 {ECO:0000312|HGNC:HGNC:10983};
GN Name=SLC25A13 {ECO:0000312|HGNC:HGNC:10983};
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), INVOLVEMENT IN CTLN2,
RP AND TISSUE SPECIFICITY.
RX PubMed=10369257; DOI=10.1038/9667;
RA Kobayashi K., Sinasac D.S., Iijima M., Boright A.P., Begum L., Lee J.R.,
RA Yasuda T., Ikeda S., Hirano R., Terazono H., Crackower M.A., Kondo I.,
RA Tsui L.-C., Scherer S.W., Saheki T.;
RT "The gene mutated in adult-onset type II citrullinaemia encodes a putative
RT mitochondrial carrier protein.";
RL Nat. Genet. 22:159-163(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND CALCIUM-BINDING.
RC TISSUE=Liver;
RX PubMed=10642534; DOI=10.1042/0264-6021:3450725;
RA Del Arco A., Agudo M., Satrustegui J.;
RT "Characterization of a second member of the subfamily of calcium-binding
RT mitochondrial carriers expressed in human non-excitable tissues.";
RL Biochem. J. 345:725-732(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=11566871; DOI=10.1093/emboj/20.18.5060;
RA Palmieri L., Pardo B., Lasorsa F.M., del Arco A., Kobayashi K., Iijima M.,
RA Runswick M.J., Walker J.E., Saheki T., Satrustegui J., Palmieri F.;
RT "Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters
RT in mitochondria.";
RL EMBO J. 20:5060-5069(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 6-251, AND INVOLVEMENT IN CTLN2.
RX PubMed=10610724; DOI=10.1006/geno.1999.6006;
RA Sinasac D.S., Crackower M.A., Lee J.R., Kobayashi K., Saheki T.,
RA Scherer S.W., Tsui L.-C.;
RT "Genomic structure of the adult-onset type II citrullinemia gene, SLC25A13,
RT and cloning and expression of its mouse homologue.";
RL Genomics 62:289-292(1999).
RN [8]
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666, 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 [11]
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 [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-453, AND IDENTIFICATION BY MASS
RP 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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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 [14]
RP VARIANT NICCD LYS-601.
RX PubMed=11793471; DOI=10.1002/humu.10022;
RA Yamaguchi N., Kobayashi K., Yasuda T., Nishi I., Iijima M., Nakagawa M.,
RA Osame M., Kondo I., Saheki T.;
RT "Screening of SLC25A13 mutations in early and late onset patients with
RT citrin deficiency and in the Japanese population: identification of two
RT novel mutations and establishment of multiple DNA diagnosis methods for
RT nine mutations.";
RL Hum. Mutat. 19:122-130(2002).
RN [15] {ECO:0007744|PDB:4P5W}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 2-320 AND 339-407 OF HOMODIMER IN
RP COMPLEX WITH CALCIUM, SUBUNIT, CALCIUM-BINDING, AND DOMAINS.
RX PubMed=25410934; DOI=10.1038/ncomms6491;
RA Thangaratnarajah C., Ruprecht J.J., Kunji E.R.;
RT "Calcium-induced conformational changes of the regulatory domain of human
RT mitochondrial aspartate/glutamate carriers.";
RL Nat. Commun. 5:5491-5491(2014).
CC -!- FUNCTION: Mitochondrial electrogenic aspartate/glutamate antiporter
CC that favors efflux of aspartate and entry of glutamate and proton
CC within the mitochondria as part of the malate-aspartate shuttle
CC (PubMed:11566871). Also mediates the uptake of L-cysteinesulfinate by
CC mitochondria in exchange of L-glutamate and proton. Can also exchange
CC L-cysteinesulfinate with aspartate in their anionic form without any
CC proton translocation (PubMed:11566871). {ECO:0000269|PubMed:11566871}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + L-aspartate(in) + L-glutamate(out) = H(+)(in) + L-
CC aspartate(out) + L-glutamate(in); Xref=Rhea:RHEA:70783,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:29991;
CC Evidence={ECO:0000269|PubMed:11566871};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-sulfino-L-alanine(out) + H(+)(in) + L-glutamate(in) = 3-
CC sulfino-L-alanine(in) + H(+)(out) + L-glutamate(out);
CC Xref=Rhea:RHEA:70967, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:61085; Evidence={ECO:0000269|PubMed:11566871};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-sulfino-L-alanine(out) + L-aspartate(in) = 3-sulfino-L-
CC alanine(in) + L-aspartate(out); Xref=Rhea:RHEA:70975,
CC ChEBI:CHEBI:29991, ChEBI:CHEBI:61085;
CC Evidence={ECO:0000250|UniProtKB:F1LZW6};
CC -!- ACTIVITY REGULATION: Activated by calcium-binding in the mitochondrial
CC intermembrane space (PubMed:11566871). Inhibited by pyridoxal 5'-
CC phosphate, bathophenathroline, mercurials, diethyl pyrocarbonate and N-
CC ethylmaleimide (PubMed:11566871). {ECO:0000269|PubMed:11566871}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=80.3 umol/min/g enzyme toward L-aspartate
CC {ECO:0000269|PubMed:11566871};
CC -!- SUBUNIT: Homodimer (via N-terminus). {ECO:0000269|PubMed:25410934}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:10642534, ECO:0000269|PubMed:11566871}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:11566871}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UJS0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UJS0-2; Sequence=VSP_043747;
CC -!- TISSUE SPECIFICITY: High levels in liver and low levels in kidney,
CC pancreas, placenta, heart and brain. {ECO:0000269|PubMed:10369257,
CC ECO:0000269|PubMed:10642534}.
CC -!- DOMAIN: The EF-hand 2 domain within the regulatory N-terminal domain
CC binds one calcium in the mitochondrial intermembrane space. Calcium
CC triggers the binding of the regulatory N-terminal domain to the C-
CC terminal domain, opening a vestibule which allows the substrates to be
CC translocated through the carrier domain (PubMed:25410934). In the
CC absence of calcium, the linker loop domain may close the vestibule and
CC prevent substrates from entering the carrier domain (By similarity).
CC {ECO:0000250|UniProtKB:O75746, ECO:0000269|PubMed:25410934}.
CC -!- DISEASE: Citrullinemia 2 (CTLN2) [MIM:603471]: A form of citrullinemia,
CC an autosomal recessive disease characterized primarily by elevated
CC serum and urine citrulline levels. Ammonia intoxication is another
CC manifestation. Citrullinemia type 2 is characterized by
CC neuropsychiatric symptoms including abnormal behaviors, loss of memory,
CC seizures and coma. Death can result from brain edema. Onset is sudden
CC and usually between the ages of 20 and 50 years.
CC {ECO:0000269|PubMed:10369257, ECO:0000269|PubMed:10610724}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cholestasis, neonatal intrahepatic, caused by citrin
CC deficiency (NICCD) [MIM:605814]: A form of citrullinemia type 2 with
CC neonatal onset, characterized by suppression of the bile flow, hepatic
CC fibrosis, low birth weight, growth retardation, hypoproteinemia,
CC variable liver dysfunction. Neonatal intrahepatic cholestasis due to
CC citrin deficiency is generally not severe and symptoms disappear by one
CC year of age with an appropriate diet. Years or even decades later,
CC however, some individuals develop the characteristic features of
CC citrullinemia type 2 with neuropsychiatric symptoms.
CC {ECO:0000269|PubMed:11793471}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB67049.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAB70112.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF118838; AAD38501.1; -; mRNA.
DR EMBL; Y17571; CAB62206.1; -; mRNA.
DR EMBL; AJ496569; CAD43091.1; -; mRNA.
DR EMBL; AC002540; AAB70112.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC002450; AAB67049.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC004458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC084368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096775; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471091; EAW76748.1; -; Genomic_DNA.
DR EMBL; BC006566; AAH06566.1; -; mRNA.
DR EMBL; AH009104; AAF28473.1; -; Genomic_DNA.
DR CCDS; CCDS55130.1; -. [Q9UJS0-2]
DR CCDS; CCDS5645.1; -. [Q9UJS0-1]
DR RefSeq; NP_001153682.1; NM_001160210.1. [Q9UJS0-2]
DR RefSeq; NP_055066.1; NM_014251.2. [Q9UJS0-1]
DR PDB; 4P5W; X-ray; 2.40 A; A/B=2-319, A/B=612-675.
DR PDBsum; 4P5W; -.
DR AlphaFoldDB; Q9UJS0; -.
DR SMR; Q9UJS0; -.
DR BioGRID; 115467; 254.
DR IntAct; Q9UJS0; 90.
DR MINT; Q9UJS0; -.
DR STRING; 9606.ENSP00000400101; -.
DR DrugBank; DB00128; Aspartic acid.
DR DrugCentral; Q9UJS0; -.
DR TCDB; 2.A.29.14.2; the mitochondrial carrier (mc) family.
DR GlyGen; Q9UJS0; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q9UJS0; -.
DR MetOSite; Q9UJS0; -.
DR PhosphoSitePlus; Q9UJS0; -.
DR SwissPalm; Q9UJS0; -.
DR BioMuta; SLC25A13; -.
DR DMDM; 13124095; -.
DR EPD; Q9UJS0; -.
DR jPOST; Q9UJS0; -.
DR MassIVE; Q9UJS0; -.
DR MaxQB; Q9UJS0; -.
DR PaxDb; Q9UJS0; -.
DR PeptideAtlas; Q9UJS0; -.
DR PRIDE; Q9UJS0; -.
DR ProteomicsDB; 84641; -. [Q9UJS0-1]
DR ProteomicsDB; 84642; -. [Q9UJS0-2]
DR Antibodypedia; 15932; 224 antibodies from 30 providers.
DR DNASU; 10165; -.
DR Ensembl; ENST00000265631.10; ENSP00000265631.6; ENSG00000004864.14. [Q9UJS0-1]
DR Ensembl; ENST00000416240.6; ENSP00000400101.2; ENSG00000004864.14. [Q9UJS0-2]
DR GeneID; 10165; -.
DR KEGG; hsa:10165; -.
DR MANE-Select; ENST00000265631.10; ENSP00000265631.6; NM_014251.3; NP_055066.1.
DR UCSC; uc003uof.5; human. [Q9UJS0-1]
DR CTD; 10165; -.
DR DisGeNET; 10165; -.
DR GeneCards; SLC25A13; -.
DR GeneReviews; SLC25A13; -.
DR HGNC; HGNC:10983; SLC25A13.
DR HPA; ENSG00000004864; Tissue enriched (liver).
DR MalaCards; SLC25A13; -.
DR MIM; 603471; phenotype.
DR MIM; 603859; gene.
DR MIM; 605814; phenotype.
DR neXtProt; NX_Q9UJS0; -.
DR OpenTargets; ENSG00000004864; -.
DR Orphanet; 247585; Citrullinemia type II.
DR Orphanet; 247598; Neonatal intrahepatic cholestasis due to citrin deficiency.
DR PharmGKB; PA35859; -.
DR VEuPathDB; HostDB:ENSG00000004864; -.
DR eggNOG; KOG0751; Eukaryota.
DR GeneTree; ENSGT00940000159344; -.
DR HOGENOM; CLU_014931_3_0_1; -.
DR InParanoid; Q9UJS0; -.
DR OMA; KRLYANL; -.
DR OrthoDB; 1007928at2759; -.
DR PhylomeDB; Q9UJS0; -.
DR TreeFam; TF313209; -.
DR PathwayCommons; Q9UJS0; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR Reactome; R-HSA-70263; Gluconeogenesis.
DR Reactome; R-HSA-8963693; Aspartate and asparagine metabolism.
DR SignaLink; Q9UJS0; -.
DR SIGNOR; Q9UJS0; -.
DR BioGRID-ORCS; 10165; 8 hits in 1078 CRISPR screens.
DR ChiTaRS; SLC25A13; human.
DR GenomeRNAi; 10165; -.
DR Pharos; Q9UJS0; Tbio.
DR PRO; PR:Q9UJS0; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UJS0; protein.
DR Bgee; ENSG00000004864; Expressed in right lobe of liver and 193 other tissues.
DR ExpressionAtlas; Q9UJS0; baseline and differential.
DR Genevisible; Q9UJS0; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0000514; F:3-sulfino-L-alanine: proton, glutamate antiporter activity; IDA:UniProtKB.
DR GO; GO:0015172; F:acidic amino acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0000515; F:aspartate:glutamate, proton antiporter activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0015183; F:L-aspartate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0009066; P:aspartate family amino acid metabolic process; TAS:Reactome.
DR GO; GO:0015810; P:aspartate transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006754; P:ATP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0045333; P:cellular respiration; IDA:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IDA:UniProtKB.
DR GO; GO:0043490; P:malate-aspartate shuttle; IDA:UniProtKB.
DR GO; GO:0006839; P:mitochondrial transport; NAS:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR029658; Aralar2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR PANTHER; PTHR45678:SF12; PTHR45678:SF12; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; SSF103506; 1.
DR SUPFAM; SSF47473; SSF47473; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Calcium; Disease variant;
KW Intrahepatic cholestasis; Membrane; Metal-binding; Methylation;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..675
FT /note="Electrogenic aspartate/glutamate antiporter
FT SLC25A13, mitochondrial"
FT /id="PRO_0000090600"
FT TOPO_DOM 2..331
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000269|PubMed:11566871"
FT TRANSMEM 332..349
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 350..392
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:11566871"
FT TRANSMEM 393..412
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 413..435
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:11566871"
FT TRANSMEM 436..449
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 450..484
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:11566871"
FT TRANSMEM 485..504
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 505..523
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:11566871"
FT TRANSMEM 524..541
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 542..580
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:11566871"
FT TRANSMEM 581..600
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT TOPO_DOM 601..675
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:11566871"
FT DOMAIN 51..86
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 87..122
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 125..157
FT /note="EF-hand 3"
FT /evidence="ECO:0000305"
FT DOMAIN 158..193
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REPEAT 326..418
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 426..510
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 518..606
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REGION 2..295
FT /note="Regulatory N-terminal domain"
FT /evidence="ECO:0000303|PubMed:25410934"
FT REGION 296..311
FT /note="Linker loop domain"
FT /evidence="ECO:0000250|UniProtKB:O75746"
FT REGION 321..612
FT /note="Carrier domain"
FT /evidence="ECO:0000303|PubMed:25410934"
FT REGION 613..675
FT /note="C-terminal domain"
FT /evidence="ECO:0000303|PubMed:25410934"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:25410934,
FT ECO:0007744|PDB:4P5W"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:25410934,
FT ECO:0007744|PDB:4P5W"
FT BINDING 70
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:25410934,
FT ECO:0007744|PDB:4P5W"
FT BINDING 72
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:25410934,
FT ECO:0007744|PDB:4P5W"
FT BINDING 77
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:25410934,
FT ECO:0007744|PDB:4P5W"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXX4"
FT MOD_RES 372
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXX4"
FT MOD_RES 453
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 484
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9QXX4"
FT MOD_RES 484
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9QXX4"
FT MOD_RES 580
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXX4"
FT MOD_RES 662
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXX4"
FT MOD_RES 666
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 311
FT /note="Q -> QQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11566871"
FT /id="VSP_043747"
FT VARIANT 141
FT /note="E -> K (in dbSNP:rs1131697)"
FT /id="VAR_050126"
FT VARIANT 232
FT /note="L -> I (in dbSNP:rs10255762)"
FT /id="VAR_050127"
FT VARIANT 601
FT /note="E -> K (in NICCD; dbSNP:rs80338727)"
FT /evidence="ECO:0000269|PubMed:11793471"
FT /id="VAR_016601"
FT CONFLICT 231..232
FT /note="EL -> VH (in Ref. 2; CAB62206)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="M -> T (in Ref. 2; CAB62206)"
FT /evidence="ECO:0000305"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:4P5W"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:4P5W"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 37..40
FT /evidence="ECO:0007829|PDB:4P5W"
FT TURN 41..44
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 55..65
FT /evidence="ECO:0007829|PDB:4P5W"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 75..86
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 90..99
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 109..118
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 120..124
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 132..138
FT /evidence="ECO:0007829|PDB:4P5W"
FT TURN 139..142
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 148..170
FT /evidence="ECO:0007829|PDB:4P5W"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 180..190
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 197..208
FT /evidence="ECO:0007829|PDB:4P5W"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 217..228
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 230..241
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 251..258
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 266..279
FT /evidence="ECO:0007829|PDB:4P5W"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 287..293
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 371..373
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 374..381
FT /evidence="ECO:0007829|PDB:4P5W"
FT HELIX 385..388
FT /evidence="ECO:0007829|PDB:4P5W"
SQ SEQUENCE 675 AA; 74176 MW; AD07EDBC6C68989B CRC64;
MAAAKVALTK RADPAELRTI FLKYASIEKN GEFFMSPNDF VTRYLNIFGE SQPNPKTVEL
LSGVVDQTKD GLISFQEFVA FESVLCAPDA LFMVAFQLFD KAGKGEVTFE DVKQVFGQTT
IHQHIPFNWD SEFVQLHFGK ERKRHLTYAE FTQFLLEIQL EHAKQAFVQR DNARTGRVTA
IDFRDIMVTI RPHVLTPFVE ECLVAAAGGT TSHQVSFSYF NGFNSLLNNM ELIRKIYSTL
AGTRKDVEVT KEEFVLAAQK FGQVTPMEVD ILFQLADLYE PRGRMTLADI ERIAPLEEGT
LPFNLAEAQR QKASGDSARP VLLQVAESAY RFGLGSVAGA VGATAVYPID LVKTRMQNQR
STGSFVGELM YKNSFDCFKK VLRYEGFFGL YRGLLPQLLG VAPEKAIKLT VNDFVRDKFM
HKDGSVPLAA EILAGGCAGG SQVIFTNPLE IVKIRLQVAG EITTGPRVSA LSVVRDLGFF
GIYKGAKACF LRDIPFSAIY FPCYAHVKAS FANEDGQVSP GSLLLAGAIA GMPAASLVTP
ADVIKTRLQV AARAGQTTYS GVIDCFRKIL REEGPKALWK GAGARVFRSS PQFGVTLLTY
ELLQRWFYID FGGVKPMGSE PVPKSRINLP APNPDHVGGY KLAVATFAGI ENKFGLYLPL
FKPSVSTSKA IGGGP
