ID   CMC1_HUMAN              Reviewed;         678 AA.
AC   O75746; B3KR64; Q96AM8;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 2.
DT   22-APR-2020, entry version 191.
DE   RecName: Full=Calcium-binding mitochondrial carrier protein Aralar1;
DE   AltName: Full=Mitochondrial aspartate glutamate carrier 1;
DE   AltName: Full=Solute carrier family 25 member 12;
GN   Name=SLC25A12; Synonyms=ARALAR1;
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), TISSUE SPECIFICITY, SUBCELLULAR
RP   LOCATION, CALCIUM-BINDING, AND TOPOLOGY.
RC   TISSUE=Heart;
RX   PubMed=9722566; DOI=10.1074/jbc.273.36.23327;
RA   Del Arco A., Satrustegui J.;
RT   "Molecular cloning of Aralar, a new member of the mitochondrial carrier
RT   superfamily that binds calcium and is present in human muscle and brain.";
RL   J. Biol. Chem. 273:23327-23334(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC   TISSUE=Heart;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Caudate nucleus;
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 GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lymph;
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   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   [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   ACETYLATION AT ALA-2, AND CLEAVAGE OF INITIATOR METHIONINE.
RX   PubMed=25489052; DOI=10.1093/hmg/ddu611;
RA   Myklebust L.M., Van Damme P., Stoeve S.I., Doerfel M.J., Abboud A.,
RA   Kalvik T.V., Grauffel C., Jonckheere V., Wu Y., Swensen J., Kaasa H.,
RA   Liszczak G., Marmorstein R., Reuter N., Lyon G.J., Gevaert K., Arnesen T.;
RT   "Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-
RT   acetylation defects.";
RL   Hum. Mol. Genet. 24:1956-1976(2015).
RN   [11]
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   [12]
RP   VARIANT EIEE39 ARG-590, AND CHARACTERIZATION OF VARIANT EIEE39 ARG-590.
RX   PubMed=19641205; DOI=10.1056/nejmoa0900591;
RA   Wibom R., Lasorsa F.M., Tohonen V., Barbaro M., Sterky F.H., Kucinski T.,
RA   Naess K., Jonsson M., Pierri C.L., Palmieri F., Wedell A.;
RT   "AGC1 deficiency associated with global cerebral hypomyelination.";
RL   N. Engl. J. Med. 361:489-495(2009).
RN   [13]
RP   ERRATUM OF PUBMED:19641205.
RA   Wibom R., Lasorsa F.M., Tohonen V., Barbaro M., Sterky F.H., Kucinski T.,
RA   Naess K., Jonsson M., Pierri C.L., Palmieri F., Wedell A.;
RL   N. Engl. J. Med. 361:731-731(2009).
RN   [14]
RP   VARIANT EIEE39 GLN-353, AND CHARACTERIZATION OF VARIANT EIEE39 GLN-353.
RX   PubMed=24515575; DOI=10.1007/8904_2013_287;
RA   Falk M.J., Li D., Gai X., McCormick E., Place E., Lasorsa F.M.,
RA   Otieno F.G., Hou C., Kim C.E., Abdel-Magid N., Vazquez L., Mentch F.D.,
RA   Chiavacci R., Liang J., Liu X., Jiang H., Giannuzzi G., Marsh E.D.,
RA   Yiran G., Tian L., Palmieri F., Hakonarson H.;
RT   "AGC1 deficiency causes infantile epilepsy, abnormal myelination, and
RT   reduced n-acetylaspartate.";
RL   JIMD Rep. 14:77-85(2014).
RN   [15] {ECO:0000244|PDB:4P5X, ECO:0000244|PDB:4P60}
RP   X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 2-311 OF HOMODIMER IN COMPLEX
RP   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 and calcium-binding carrier that catalyzes the
CC       calcium-dependent exchange of cytoplasmic glutamate with mitochondrial
CC       aspartate across the mitochondrial inner membrane (PubMed:11566871,
CC       PubMed:25410934). May have a function in the urea cycle
CC       (PubMed:11566871). {ECO:0000269|PubMed:11566871,
CC       ECO:0000269|PubMed:25410934}.
CC   -!- SUBUNIT: Homodimer (via N-terminus). {ECO:0000269|PubMed:25410934}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000269|PubMed:9722566}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:9722566}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O75746-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O75746-2; Sequence=VSP_054469;
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in the heart and skeletal
CC       muscle, weakly in brain and kidney. {ECO:0000269|PubMed:10369257,
CC       ECO:0000269|PubMed:9722566}.
CC   -!- DOMAIN: Upon calcium binding, the EF-hand-containing regulatory N-
CC       terminal domain binds to the C-terminal domain, opening a vestibule
CC       which allows the substrates to be translocated through the carrier
CC       domain (PubMed:25410934). In the absence of calcium, the linker loop
CC       domain may close the vestibule, which may prevent substrates from
CC       entering the carrier domain (PubMed:25410934).
CC       {ECO:0000269|PubMed:25410934}.
CC   -!- DISEASE: Epileptic encephalopathy, early infantile, 39 (EIEE39)
CC       [MIM:612949]: A form of epileptic encephalopathy, a heterogeneous group
CC       of severe childhood onset epilepsies characterized by refractory
CC       seizures, neurodevelopmental impairment, and poor prognosis.
CC       Development is normal prior to seizure onset, after which cognitive and
CC       motor delays become apparent. EIEE39 is characterized by global
CC       hypomyelination of the central nervous system, with the gray matter
CC       appearing relatively unaffected. Inheritance is autosomal recessive.
CC       {ECO:0000269|PubMed:19641205, ECO:0000269|PubMed:24515575}. Note=The
CC       disease is caused by mutations affecting the gene represented in this
CC       entry.
CC   -!- MISCELLANEOUS: Binds to one calcium ion with high affinity.
CC       {ECO:0000269|PubMed:25410934, ECO:0000269|PubMed:9722566}.
CC   -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC       {ECO:0000305}.
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DR   EMBL; Y14494; CAA74834.1; -; mRNA.
DR   EMBL; AJ496568; CAD43090.1; -; mRNA.
DR   EMBL; AK091071; BAG52276.1; -; mRNA.
DR   EMBL; AC015976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC068039; AAY24134.1; -; Genomic_DNA.
DR   EMBL; AC114745; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471058; EAX11196.1; -; Genomic_DNA.
DR   EMBL; BC016932; AAH16932.1; -; mRNA.
DR   CCDS; CCDS33327.1; -. [O75746-1]
DR   RefSeq; NP_003696.2; NM_003705.4. [O75746-1]
DR   PDB; 4P5X; X-ray; 2.26 A; A=2-311.
DR   PDB; 4P60; X-ray; 2.40 A; A/B=2-311.
DR   PDBsum; 4P5X; -.
DR   PDBsum; 4P60; -.
DR   SMR; O75746; -.
DR   BioGrid; 114164; 54.
DR   IntAct; O75746; 42.
DR   MINT; O75746; -.
DR   STRING; 9606.ENSP00000388658; -.
DR   DrugBank; DB00128; Aspartic acid.
DR   DrugCentral; O75746; -.
DR   TCDB; 2.A.29.14.1; the mitochondrial carrier (mc) family.
DR   iPTMnet; O75746; -.
DR   PhosphoSitePlus; O75746; -.
DR   SwissPalm; O75746; -.
DR   BioMuta; SLC25A12; -.
DR   EPD; O75746; -.
DR   jPOST; O75746; -.
DR   MassIVE; O75746; -.
DR   MaxQB; O75746; -.
DR   PaxDb; O75746; -.
DR   PeptideAtlas; O75746; -.
DR   PRIDE; O75746; -.
DR   ProteomicsDB; 3583; -.
DR   ProteomicsDB; 50177; -. [O75746-1]
DR   Antibodypedia; 33855; 202 antibodies.
DR   DNASU; 8604; -.
DR   Ensembl; ENST00000422440; ENSP00000388658; ENSG00000115840. [O75746-1]
DR   GeneID; 8604; -.
DR   KEGG; hsa:8604; -.
DR   UCSC; uc002uhh.4; human. [O75746-1]
DR   CTD; 8604; -.
DR   DisGeNET; 8604; -.
DR   GeneCards; SLC25A12; -.
DR   HGNC; HGNC:10982; SLC25A12.
DR   HPA; ENSG00000115840; Tissue enhanced (skeletal).
DR   MalaCards; SLC25A12; -.
DR   MIM; 603667; gene.
DR   MIM; 612949; phenotype.
DR   neXtProt; NX_O75746; -.
DR   OpenTargets; ENSG00000115840; -.
DR   Orphanet; 353217; Epileptic encephalopathy with global cerebral demyelination.
DR   PharmGKB; PA35858; -.
DR   eggNOG; KOG0751; Eukaryota.
DR   eggNOG; ENOG410XNRM; LUCA.
DR   GeneTree; ENSGT00940000155963; -.
DR   HOGENOM; CLU_014931_3_0_1; -.
DR   InParanoid; O75746; -.
DR   KO; K15105; -.
DR   OMA; KKDFFGE; -.
DR   OrthoDB; 1007928at2759; -.
DR   PhylomeDB; O75746; -.
DR   TreeFam; TF313209; -.
DR   Reactome; R-HSA-1268020; Mitochondrial protein import.
DR   Reactome; R-HSA-70263; Gluconeogenesis.
DR   Reactome; R-HSA-8963693; Aspartate and asparagine metabolism.
DR   ChiTaRS; SLC25A12; human.
DR   GeneWiki; SLC25A12; -.
DR   GenomeRNAi; 8604; -.
DR   Pharos; O75746; Tbio.
DR   PRO; PR:O75746; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; O75746; protein.
DR   Bgee; ENSG00000115840; Expressed in muscle of leg and 225 other tissues.
DR   ExpressionAtlas; O75746; baseline and differential.
DR   Genevisible; O75746; HS.
DR   GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR   GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; 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; IDA:UniProtKB.
DR   GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0015810; P:aspartate transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR   GO; GO:0006537; P:glutamate biosynthetic process; IEA:Ensembl.
DR   GO; GO:0015813; P:L-glutamate transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0043490; P:malate-aspartate shuttle; IDA:UniProtKB.
DR   GO; GO:1904024; P:negative regulation of glucose catabolic process to lactate via pyruvate; IEA:Ensembl.
DR   GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IEA:Ensembl.
DR   GO; GO:0010907; P:positive regulation of glucose metabolic process; IEA:Ensembl.
DR   GO; GO:0031643; P:positive regulation of myelination; IEA:Ensembl.
DR   GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
DR   Gene3D; 1.50.40.10; -; 1.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR018247; EF_Hand_1_Ca_BS.
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   Pfam; PF00153; Mito_carr; 3.
DR   PRINTS; PR00926; MITOCARRIER.
DR   SMART; SM00054; EFh; 3.
DR   SUPFAM; SSF103506; SSF103506; 1.
DR   SUPFAM; SSF47473; SSF47473; 2.
DR   PROSITE; PS00018; EF_HAND_1; 1.
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 mutation;
KW   Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW   Polymorphism; Reference proteome; Repeat; Transmembrane;
KW   Transmembrane helix; Transport.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|PubMed:22814378,
FT                   ECO:0000269|PubMed:25489052"
FT   CHAIN           2..678
FT                   /note="Calcium-binding mitochondrial carrier protein
FT                   Aralar1"
FT                   /id="PRO_0000090598"
FT   TRANSMEM        330..347
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000305|PubMed:9722566"
FT   TRANSMEM        391..410
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000305|PubMed:9722566"
FT   TRANSMEM        434..447
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000305|PubMed:9722566"
FT   TRANSMEM        483..502
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000305|PubMed:9722566"
FT   TRANSMEM        522..539
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000305|PubMed:9722566"
FT   TRANSMEM        579..598
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000305|PubMed:9722566"
FT   DOMAIN          65..76
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          86..121
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          125..155
FT                   /note="EF-hand 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          157..192
FT                   /note="EF-hand 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REPEAT          324..416
FT                   /note="Solcar 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT   REPEAT          424..508
FT                   /note="Solcar 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT   REPEAT          516..604
FT                   /note="Solcar 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT   CA_BIND         65..76
FT                   /note="1"
FT                   /evidence="ECO:0000269|PubMed:25410934"
FT   CA_BIND         99..110
FT                   /note="2"
FT   CA_BIND         170..181
FT                   /note="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REGION          2..294
FT                   /note="N-terminal domain"
FT                   /evidence="ECO:0000303|PubMed:25410934"
FT   REGION          295..310
FT                   /note="Linker loop domain"
FT                   /evidence="ECO:0000303|PubMed:25410934"
FT   REGION          320..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   METAL           65
FT                   /note="Calcium"
FT                   /evidence="ECO:0000244|PDB:4P5X,
FT                   ECO:0000269|PubMed:25410934"
FT   METAL           67
FT                   /note="Calcium"
FT                   /evidence="ECO:0000244|PDB:4P5X,
FT                   ECO:0000269|PubMed:25410934"
FT   METAL           69
FT                   /note="Calcium"
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   METAL           71
FT                   /note="Calcium; via carbonyl oxygen"
FT                   /evidence="ECO:0000244|PDB:4P5X,
FT                   ECO:0000269|PubMed:25410934"
FT   METAL           76
FT                   /note="Calcium"
FT                   /evidence="ECO:0000244|PDB:4P5X,
FT                   ECO:0000269|PubMed:25410934"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000244|PubMed:22814378,
FT                   ECO:0000269|PubMed:25489052"
FT   VAR_SEQ         1..108
FT                   /note="MAVKVQTTKRGDPHELRNIFLQYASTEVDGERYMTPEDFVQRYLGLYNDPNS
FT                   NPKIVQLLAGVADQTKDGLISYQEFLAFESVLCAPDSMFIVAFQLFDKSGNGEVTF ->
FT                   M (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_054469"
FT   VARIANT         353
FT                   /note="R -> Q (in EIEE39; significant loss in ability to
FT                   transport aspartate or glutamate; dbSNP:rs886037851)"
FT                   /evidence="ECO:0000269|PubMed:24515575"
FT                   /id="VAR_071976"
FT   VARIANT         473
FT                   /note="R -> Q (in dbSNP:rs35565687)"
FT                   /id="VAR_047917"
FT   VARIANT         590
FT                   /note="Q -> R (in EIEE39; the mutant protein is unable to
FT                   transport aspartate or glutamate although it is able to
FT                   integrate normally into the inner mitochondrial membrane;
FT                   dbSNP:rs121434396)"
FT                   /evidence="ECO:0000269|PubMed:19641205"
FT                   /id="VAR_063253"
FT   CONFLICT        596..597
FT                   /note="VT -> AH (in Ref. 1; CAA74834)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        600
FT                   /note="L -> V (in Ref. 1; CAA74834)"
FT                   /evidence="ECO:0000305"
FT   HELIX           15..23
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   STRAND          26..28
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   STRAND          31..34
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           36..40
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   TURN            41..43
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           54..64
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   STRAND          69..71
FT                   /evidence="ECO:0000244|PDB:4P60"
FT   HELIX           74..84
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           89..98
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           108..117
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   STRAND          128..130
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           131..137
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   TURN            138..141
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           147..169
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   STRAND          174..177
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           179..189
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           191..193
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           196..200
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           202..205
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   TURN            206..210
FT                   /evidence="ECO:0000244|PDB:4P60"
FT   STRAND          212..215
FT                   /evidence="ECO:0000244|PDB:4P60"
FT   HELIX           216..227
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           229..238
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           250..257
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   TURN            258..261
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           265..276
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   STRAND          282..284
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   HELIX           286..292
FT                   /evidence="ECO:0000244|PDB:4P5X"
FT   STRAND          300..302
FT                   /evidence="ECO:0000244|PDB:4P60"
FT   TURN            305..307
FT                   /evidence="ECO:0000244|PDB:4P60"
SQ   SEQUENCE   678 AA;  74762 MW;  D00A7D3D4244539F CRC64;
     MAVKVQTTKR GDPHELRNIF LQYASTEVDG ERYMTPEDFV QRYLGLYNDP NSNPKIVQLL
     AGVADQTKDG LISYQEFLAF ESVLCAPDSM FIVAFQLFDK SGNGEVTFEN VKEIFGQTII
     HHHIPFNWDC EFIRLHFGHN RKKHLNYTEF TQFLQELQLE HARQAFALKD KSKSGMISGL
     DFSDIMVTIR SHMLTPFVEE NLVSAAGGSI SHQVSFSYFN AFNSLLNNME LVRKIYSTLA
     GTRKDVEVTK EEFAQSAIRY GQVTPLEIDI LYQLADLYNA SGRLTLADIE RIAPLAEGAL
     PYNLAELQRQ QSPGLGRPIW LQIAESAYRF TLGSVAGAVG ATAVYPIDLV KTRMQNQRGS
     GSVVGELMYK NSFDCFKKVL RYEGFFGLYR GLIPQLIGVA PEKAIKLTVN DFVRDKFTRR
     DGSVPLPAEV LAGGCAGGSQ VIFTNPLEIV KIRLQVAGEI TTGPRVSALN VLRDLGIFGL
     YKGAKACFLR DIPFSAIYFP VYAHCKLLLA DENGHVGGLN LLAAGAMAGV PAASLVTPAD
     VIKTRLQVAA RAGQTTYSGV IDCFRKILRE EGPSAFWKGT AARVFRSSPQ FGVTLVTYEL
     LQRWFYIDFG GLKPAGSEPT PKSRIADLPP ANPDHIGGYR LATATFAGIE NKFGLYLPKF
     KSPSVAVVQP KAAVAATQ
//