NCLX_HUMAN
ID NCLX_HUMAN Reviewed; 584 AA.
AC Q6J4K2; A6NP50; Q4KMS9; Q6J4K1; Q9H6I8;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Mitochondrial sodium/calcium exchanger protein {ECO:0000305};
DE AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 6 {ECO:0000250|UniProtKB:Q925Q3};
DE AltName: Full=Sodium/calcium exchanger protein, mitochondrial {ECO:0000303|PubMed:15060069};
DE AltName: Full=Sodium/potassium/calcium exchanger 6 {ECO:0000250|UniProtKB:Q925Q3};
DE AltName: Full=Solute carrier family 24 member 6 {ECO:0000312|HGNC:HGNC:26175};
DE AltName: Full=Solute carrier family 8 member B1 {ECO:0000312|HGNC:HGNC:26175};
DE Flags: Precursor;
GN Name=SLC8B1 {ECO:0000312|HGNC:HGNC:26175};
GN Synonyms=NCKX6 {ECO:0000250|UniProtKB:Q925Q3},
GN NCLX {ECO:0000303|PubMed:15060069}, SLC24A6 {ECO:0000312|HGNC:HGNC:26175};
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] (ISOFORMS 1 AND 2), FUNCTION, AND ACTIVITY
RP REGULATION.
RX PubMed=15060069; DOI=10.1074/jbc.m401229200;
RA Palty R., Ohana E., Hershfinkel M., Volokita M., Elgazar V., Beharier O.,
RA Silverman W.F., Argaman M., Sekler I.;
RT "Lithium-calcium exchange is mediated by a distinct potassium-independent
RT sodium-calcium exchanger.";
RL J. Biol. Chem. 279:25234-25240(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
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] (ISOFORM 1).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 185-584 (ISOFORM 1).
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20018762; DOI=10.1073/pnas.0908099107;
RA Palty R., Silverman W.F., Hershfinkel M., Caporale T., Sensi S.L.,
RA Parnis J., Nolte C., Fishman D., Shoshan-Barmatz V., Herrmann S.,
RA Khananshvili D., Sekler I.;
RT "NCLX is an essential component of mitochondrial Na+/Ca2+ exchange.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:436-441(2010).
RN [7]
RP FUNCTION.
RX PubMed=22829870; DOI=10.1371/journal.pone.0039722;
RA Tarasov A.I., Semplici F., Ravier M.A., Bellomo E.A., Pullen T.J.,
RA Gilon P., Sekler I., Rizzuto R., Rutter G.A.;
RT "The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP
RT increases in pancreatic beta-cells.";
RL PLoS ONE 7:E39722-E39722(2012).
RN [8]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=23056385; DOI=10.1371/journal.pone.0046649;
RA Nita I.I., Hershfinkel M., Fishman D., Ozeri E., Rutter G.A., Sensi S.L.,
RA Khananshvili D., Lewis E.C., Sekler I.;
RT "The mitochondrial na(+)/ca(2+) exchanger upregulates glucose dependent
RT ca(2+) signalling linked to insulin secretion.";
RL PLoS ONE 7:E46649-E46649(2012).
RN [9]
RP FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=24898248; DOI=10.1074/jbc.m113.540898;
RA De Marchi U., Santo-Domingo J., Castelbou C., Sekler I., Wiederkehr A.,
RA Demaurex N.;
RT "NCLX protein, but not LETM1, mediates mitochondrial Ca2+ extrusion,
RT thereby limiting Ca2+-induced NAD(P)H production and modulating matrix
RT redox state.";
RL J. Biol. Chem. 289:20377-20385(2014).
RN [10]
RP PHOSPHORYLATION AT SER-258, AND MUTAGENESIS OF SER-258.
RX PubMed=26440884; DOI=10.1016/j.celrep.2015.08.079;
RA Kostic M., Ludtmann M.H., Bading H., Hershfinkel M., Steer E., Chu C.T.,
RA Abramov A.Y., Sekler I.;
RT "PKA phosphorylation of NCLX reverses mitochondrial calcium overload and
RT depolarization, promoting survival of PINK1-deficient dopaminergic
RT neurons.";
RL Cell Rep. 13:376-386(2015).
RN [11]
RP FUNCTION.
RX PubMed=28219928; DOI=10.15252/embj.201592481;
RA Ben-Kasus Nissim T., Zhang X., Elazar A., Roy S., Stolwijk J.A., Zhou Y.,
RA Motiani R.K., Gueguinou M., Hempel N., Hershfinkel M., Gill D.L.,
RA Trebak M., Sekler I.;
RT "Mitochondria control store-operated Ca(2+) entry through Na(+) and redox
RT signals.";
RL EMBO J. 36:797-815(2017).
CC -!- FUNCTION: Mitochondrial sodium/calcium antiporter that mediates sodium-
CC dependent calcium efflux from mitochondrion, by mediating the exchange
CC of 3 sodium ions per 1 calcium ion (PubMed:20018762, PubMed:22829870,
CC PubMed:23056385, PubMed:24898248, PubMed:28219928). Plays a central
CC role in mitochondrial calcium homeostasis by mediating mitochondrial
CC calcium extrusion: calcium efflux is essential for mitochondrial
CC function and cell survival, notably in cardiomyocytes (By similarity).
CC Regulates rates of glucose-dependent insulin secretion in pancreatic
CC beta-cells during the first phase of insulin secretion: acts by
CC mediating efflux of calcium from mitochondrion, thereby affecting
CC cytoplasmic calcium responses (PubMed:23056385). Required for store-
CC operated Ca(2+) entry (SOCE) and Ca(2+) release-activated Ca(2+) (CRAC)
CC channel regulation: sodium transport by SLC8B1 leads to promote
CC calcium-shuttling that modulates mitochondrial redox status, thereby
CC regulating SOCE activity (PubMed:28219928). Involved in B-lymphocyte
CC chemotaxis (By similarity). Able to transport Ca(2+) in exchange of
CC either Li(+) or Na(+), explaining how Li(+) catalyzes Ca(2+) exchange
CC (PubMed:15060069). In contrast to other members of the family its
CC function is independent of K(+) (PubMed:15060069).
CC {ECO:0000250|UniProtKB:Q925Q3, ECO:0000269|PubMed:15060069,
CC ECO:0000269|PubMed:20018762, ECO:0000269|PubMed:22829870,
CC ECO:0000269|PubMed:23056385, ECO:0000269|PubMed:24898248,
CC ECO:0000269|PubMed:28219928}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Ca(2+)(in) + 3 Na(+)(out) = Ca(2+)(out) + 3 Na(+)(in);
CC Xref=Rhea:RHEA:69955, ChEBI:CHEBI:29101, ChEBI:CHEBI:29108;
CC Evidence={ECO:0000305|PubMed:23056385, ECO:0000305|PubMed:24898248};
CC -!- ACTIVITY REGULATION: Inhibited by the sodium/calcium exchanger
CC inhibitor CGP-37157 (PubMed:24898248). Strongly inhibited by zinc
CC (PubMed:15060069). {ECO:0000269|PubMed:15060069,
CC ECO:0000269|PubMed:24898248}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:20018762, ECO:0000269|PubMed:23056385}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:20018762,
CC ECO:0000269|PubMed:23056385}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6J4K2-1; Sequence=Displayed;
CC Name=2; Synonyms=S-NCLX {ECO:0000303|PubMed:15060069};
CC IsoId=Q6J4K2-2; Sequence=VSP_016996;
CC -!- TISSUE SPECIFICITY: Present in pancreatic beta-cells (at protein
CC level). {ECO:0000269|PubMed:23056385}.
CC -!- PTM: Phosphorylation at Ser-258 by PKA prevents calcium overload.
CC {ECO:0000269|PubMed:26440884}.
CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC family. SLC24A subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15271.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY601759; AAT35807.1; -; mRNA.
DR EMBL; AY601760; AAT35808.1; -; mRNA.
DR EMBL; AC010178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW98050.1; -; Genomic_DNA.
DR EMBL; BC098360; AAH98360.1; -; mRNA.
DR EMBL; AK025886; BAB15271.1; ALT_INIT; mRNA.
DR CCDS; CCDS31909.1; -. [Q6J4K2-1]
DR CCDS; CCDS81744.1; -. [Q6J4K2-2]
DR RefSeq; NP_001317395.1; NM_001330466.1. [Q6J4K2-2]
DR RefSeq; NP_079235.2; NM_024959.3. [Q6J4K2-1]
DR RefSeq; XP_006719670.1; XM_006719607.2.
DR RefSeq; XP_011537051.1; XM_011538749.2.
DR RefSeq; XP_011537054.1; XM_011538752.2.
DR AlphaFoldDB; Q6J4K2; -.
DR BioGRID; 123078; 3.
DR IntAct; Q6J4K2; 1.
DR STRING; 9606.ENSP00000447091; -.
DR BindingDB; Q6J4K2; -.
DR ChEMBL; CHEMBL3763001; -.
DR GuidetoPHARMACOLOGY; 1050; -.
DR TCDB; 2.A.19.4.4; the ca(2+):cation antiporter (caca) family.
DR GlyGen; Q6J4K2; 1 site.
DR iPTMnet; Q6J4K2; -.
DR PhosphoSitePlus; Q6J4K2; -.
DR BioMuta; SLC8B1; -.
DR DMDM; 85681048; -.
DR jPOST; Q6J4K2; -.
DR MassIVE; Q6J4K2; -.
DR MaxQB; Q6J4K2; -.
DR PaxDb; Q6J4K2; -.
DR PeptideAtlas; Q6J4K2; -.
DR PRIDE; Q6J4K2; -.
DR ProteomicsDB; 66508; -. [Q6J4K2-1]
DR ProteomicsDB; 66509; -. [Q6J4K2-2]
DR Antibodypedia; 31257; 98 antibodies from 26 providers.
DR DNASU; 80024; -.
DR Ensembl; ENST00000202831.7; ENSP00000202831.3; ENSG00000089060.12. [Q6J4K2-1]
DR Ensembl; ENST00000546737.5; ENSP00000450081.1; ENSG00000089060.12. [Q6J4K2-2]
DR Ensembl; ENST00000552014.5; ENSP00000447091.1; ENSG00000089060.12. [Q6J4K2-1]
DR Ensembl; ENST00000680972.1; ENSP00000506377.1; ENSG00000089060.12. [Q6J4K2-1]
DR GeneID; 80024; -.
DR KEGG; hsa:80024; -.
DR MANE-Select; ENST00000680972.1; ENSP00000506377.1; NM_001358345.2; NP_001345274.1.
DR UCSC; uc001tvc.4; human. [Q6J4K2-1]
DR CTD; 80024; -.
DR DisGeNET; 80024; -.
DR GeneCards; SLC8B1; -.
DR HGNC; HGNC:26175; SLC8B1.
DR HPA; ENSG00000089060; Tissue enhanced (adrenal).
DR MIM; 609841; gene.
DR neXtProt; NX_Q6J4K2; -.
DR OpenTargets; ENSG00000089060; -.
DR PharmGKB; PA134954965; -.
DR VEuPathDB; HostDB:ENSG00000089060; -.
DR eggNOG; KOG2399; Eukaryota.
DR GeneTree; ENSGT00940000157433; -.
DR HOGENOM; CLU_004979_3_2_1; -.
DR InParanoid; Q6J4K2; -.
DR OMA; IYLWQAV; -.
DR OrthoDB; 478735at2759; -.
DR PhylomeDB; Q6J4K2; -.
DR TreeFam; TF323444; -.
DR PathwayCommons; Q6J4K2; -.
DR Reactome; R-HSA-425561; Sodium/Calcium exchangers.
DR Reactome; R-HSA-8949215; Mitochondrial calcium ion transport.
DR SignaLink; Q6J4K2; -.
DR BioGRID-ORCS; 80024; 14 hits in 1065 CRISPR screens.
DR ChiTaRS; SLC8B1; human.
DR GenomeRNAi; 80024; -.
DR Pharos; Q6J4K2; Tbio.
DR PRO; PR:Q6J4K2; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q6J4K2; protein.
DR Bgee; ENSG00000089060; Expressed in left adrenal gland cortex and 153 other tissues.
DR ExpressionAtlas; Q6J4K2; baseline and differential.
DR Genevisible; Q6J4K2; HS.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0030061; C:mitochondrial crista; IDA:BHF-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0015368; F:calcium:cation antiporter activity; TAS:Reactome.
DR GO; GO:0005432; F:calcium:sodium antiporter activity; IDA:UniProtKB.
DR GO; GO:0086038; F:calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential; ISS:UniProtKB.
DR GO; GO:0008324; F:cation transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0099093; P:calcium export from the mitochondrion; IDA:UniProtKB.
DR GO; GO:0006812; P:cation transport; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0042593; P:glucose homeostasis; IDA:UniProtKB.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; TAS:BHF-UCL.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IMP:BHF-UCL.
DR GO; GO:0050796; P:regulation of insulin secretion; IDA:UniProtKB.
DR GO; GO:1901623; P:regulation of lymphocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; IDA:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1420.30; -; 2.
DR InterPro; IPR004837; NaCa_Exmemb.
DR InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR Pfam; PF01699; Na_Ca_ex; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiport; Calcium; Calcium transport; Glycoprotein;
KW Ion transport; Lithium; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Reference proteome;
KW Sensory transduction; Sodium; Sodium transport; Transit peptide;
KW Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..584
FT /note="Mitochondrial sodium/calcium exchanger protein"
FT /id="PRO_0000045756"
FT TOPO_DOM 27..95
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..168
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..226
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..360
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..383
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 384..404
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 405..416
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 417..437
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 438..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 467..487
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 488..508
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 509..524
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 525..545
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 546..558
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 559..579
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255"
FT TOPO_DOM 580..584
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 258
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:26440884"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 176..231
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15060069"
FT /id="VSP_016996"
FT VARIANT 222
FT /note="R -> C (in dbSNP:rs16942745)"
FT /id="VAR_050224"
FT VARIANT 358
FT /note="L -> F (in dbSNP:rs3764034)"
FT /id="VAR_050225"
FT MUTAGEN 258
FT /note="S->A: Abolished ability to prevent calcium
FT overload."
FT /evidence="ECO:0000269|PubMed:26440884"
FT MUTAGEN 258
FT /note="S->D: Phosphomimetic mutant; prevents calcium
FT overload."
FT /evidence="ECO:0000269|PubMed:26440884"
FT CONFLICT 57
FT /note="C -> R (in Ref. 1; AAT35807)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="S -> P (in Ref. 1; AAT35807)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="N -> S (in Ref. 1; AAT35807)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 584 AA; 64231 MW; 6B7008661CC12872 CRC64;
MAGRRLNLRW ALSVLCVLLM AETVSGTRGS STGAHISPQF PASGVNQTPV VDCRKVCGLN
VSDRCDFIRT NPDCHSDGGY LDYLEGIFCH FPPSLLPLAV TLYVSWLLYL FLILGVTAAK
FFCPNLSAIS TTLKLSHNVA GVTFLAFGNG APDIFSALVA FSDPHTAGLA LGALFGAGVL
VTTVVAGGIT ILHPFMAASR PFFRDIVFYM VAVFLTFLML FRGRVTLAWA LGYLGLYVFY
VVTVILCTWI YQRQRRGSLF CPMPVTPEIL SDSEEDRVSS NTNSYDYGDE YRPLFFYQET
TAQILVRALN PLDYMKWRRK SAYWKALKVF KLPVEFLLLL TVPVVDPDKD DQNWKRPLNC
LHLVISPLVV VLTLQSGTYG VYEIGGLVPV WVVVVIAGTA LASVTFFATS DSQPPRLHWL
FAFLGFLTSA LWINAAATEV VNILRSLGVV FRLSNTVLGL TLLAWGNSIG DAFSDFTLAR
QGYPRMAFSA CFGGIIFNIL VGVGLGCLLQ ISRSHTEVKL EPDGLLVWVL AGALGLSLVF
SLVSVPLQCF QLSRVYGFCL LLFYLNFLVV ALLTEFGVIH LKSM
