NAC3_MOUSE
ID NAC3_MOUSE Reviewed; 928 AA.
AC S4R2P9; Q7TS90; Q8VHJ8;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Sodium/calcium exchanger 3;
DE AltName: Full=Na(+)/Ca(2+)-exchange protein 3;
DE AltName: Full=Solute carrier family 8 member 3;
DE Flags: Precursor;
GN Name=Slc8a3 {ECO:0000312|MGI:MGI:107976};
GN Synonyms=Ncx3 {ECO:0000303|PubMed:21959935, ECO:0000303|PubMed:24616101};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAL39160.1};
RC TISSUE=Skeletal muscle {ECO:0000312|EMBL:AAL39160.1};
RA Kraev A.;
RT "Towards complete inventory of calcium transporters of the house mouse.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE38073.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAE38073.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000138735,
RC ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH52435.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH52435.1};
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 DISRUPTION PHENOTYPE, FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=14722618; DOI=10.1172/jci200418688;
RA Sokolow S., Manto M., Gailly P., Molgo J., Vandebrouck C.,
RA Vanderwinden J.M., Herchuelz A., Schurmans S.;
RT "Impaired neuromuscular transmission and skeletal muscle fiber necrosis in
RT mice lacking Na/Ca exchanger 3.";
RL J. Clin. Invest. 113:265-273(2004).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, TRANSPORTER ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=21593315; DOI=10.1523/jneurosci.6296-10.2011;
RA Molinaro P., Viggiano D., Nistico R., Sirabella R., Secondo A., Boscia F.,
RA Pannaccione A., Scorziello A., Mehdawy B., Sokolow S., Herchuelz A.,
RA Di Renzo G.F., Annunziato L.;
RT "Na+ -Ca2+ exchanger (NCX3) knock-out mice display an impairment in
RT hippocampal long-term potentiation and spatial learning and memory.";
RL J. Neurosci. 31:7312-7321(2011).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21959935; DOI=10.1038/cdd.2011.125;
RA Boscia F., D'Avanzo C., Pannaccione A., Secondo A., Casamassa A.,
RA Formisano L., Guida N., Sokolow S., Herchuelz A., Annunziato L.;
RT "Silencing or knocking out the Na(+)/Ca(2+) exchanger-3 (NCX3) impairs
RT oligodendrocyte differentiation.";
RL Cell Death Differ. 19:562-572(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH AKAP1, AND TISSUE
RP SPECIFICITY.
RX PubMed=24101730; DOI=10.1242/jcs.129668;
RA Scorziello A., Savoia C., Sisalli M.J., Adornetto A., Secondo A.,
RA Boscia F., Esposito A., Polishchuk E.V., Polishchuk R.S., Molinaro P.,
RA Carlucci A., Lignitto L., Di Renzo G., Feliciello A., Annunziato L.;
RT "NCX3 regulates mitochondrial Ca(2+) handling through the AKAP121-anchored
RT signaling complex and prevents hypoxia-induced neuronal death.";
RL J. Cell Sci. 126:5566-5577(2013).
RN [9]
RP REVIEW.
RX PubMed=23506867; DOI=10.1016/j.mam.2012.07.003;
RA Khananshvili D.;
RT "The SLC8 gene family of sodium-calcium exchangers (NCX) - structure,
RT function, and regulation in health and disease.";
RL Mol. Aspects Med. 34:220-235(2013).
RN [10]
RP FUNCTION (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2),
RP TISSUE SPECIFICITY (ISOFORMS 1 AND 2), AND ACTIVITY REGULATION (ISOFORMS 1
RP AND 2).
RX PubMed=24616101; DOI=10.1074/jbc.m113.529388;
RA Michel L.Y., Verkaart S., Koopman W.J., Willems P.H., Hoenderop J.G.,
RA Bindels R.J.;
RT "Function and regulation of the Na+-Ca2+ exchanger NCX3 splice variants in
RT brain and skeletal muscle.";
RL J. Biol. Chem. 289:11293-11303(2014).
RN [11] {ECO:0007744|PDB:2LT9}
RP STRUCTURE BY NMR OF 528-675.
RX PubMed=22806131; DOI=10.1007/s10858-012-9654-1;
RA Breukels V., Touw W.G., Vuister G.W.;
RT "NMR structure note: solution structure of Ca binding domain 2B of the
RT third isoform of the Na/Ca exchanger.";
RL J. Biomol. NMR 54:115-121(2012).
CC -!- FUNCTION: Mediates the electrogenic exchange of Ca(2+) against Na(+)
CC ions across the cell membrane, and thereby contributes to the
CC regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular
CC processes. Contributes to cellular Ca(2+) homeostasis in excitable
CC cells, both in muscle and in brain (PubMed:14722618, PubMed:21593315).
CC In a first phase, voltage-gated channels mediate the rapid increase of
CC cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the
CC endoplasmic reticulum. SLC8A3 mediates the export of Ca(2+) from the
CC cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly
CC return to baseline (PubMed:14722618, PubMed:21593315). Contributes to
CC Ca(2+) transport during excitation-contraction coupling in muscle
CC (PubMed:14722618). In neurons, contributes to the rapid decrease of
CC cytoplasmic Ca(2+) levels back to baseline after neuronal activation,
CC and thereby contributes to modulate synaptic plasticity, learning and
CC memory (PubMed:21593315). Required for normal oligodendrocyte
CC differentiation and for normal myelination (PubMed:21959935). Mediates
CC Ca(2+) efflux from mitochondria and contributes to mitochondrial Ca(2+)
CC ion homeostasis (PubMed:24616101). Isoform 1 displays higher calcium
CC exchanger activity than isoform 2, probably because isoform 1 has a
CC lower threshold for activation by cytoplasmic Ca(2+) (PubMed:24616101).
CC {ECO:0000269|PubMed:14722618, ECO:0000269|PubMed:21593315,
CC ECO:0000269|PubMed:21959935, ECO:0000269|PubMed:24616101}.
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:14722618, ECO:0000305|PubMed:21593315};
CC -!- ACTIVITY REGULATION: Calcium transport is stimulated by cytoplasmic
CC Ca(2+) and is inhibited by Na(+). Isoform 1 is more sensitive to
CC stimulation by Ca(2+) than isoform 2. Isoform 2 is more sensitive to
CC inactivation by Na(+). {ECO:0000269|PubMed:24616101}.
CC -!- SUBUNIT: Interacts with AKAP1. {ECO:0000269|PubMed:24616101}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14722618,
CC ECO:0000269|PubMed:24101730}; Multi-pass membrane protein
CC {ECO:0000305}. Perikaryon {ECO:0000250|UniProtKB:P70549}. Cell
CC projection, dendrite {ECO:0000250|UniProtKB:P70549}. Cell projection,
CC dendritic spine {ECO:0000250|UniProtKB:P70549}. Cell membrane,
CC sarcolemma {ECO:0000269|PubMed:14722618}. Cytoplasm, sarcoplasm
CC {ECO:0000269|PubMed:14722618}. Cell junction
CC {ECO:0000269|PubMed:14722618}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:24101730}; Multi-pass membrane protein
CC {ECO:0000305}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P57103}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:24101730}; Multi-pass membrane protein
CC {ECO:0000305}. Note=Detected at neuromuscular junctions.
CC {ECO:0000269|PubMed:14722618}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:24616101}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:24616101}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=NCX3-AC {ECO:0000303|PubMed:24616101};
CC IsoId=S4R2P9-1; Sequence=Displayed;
CC Name=2; Synonyms=NCX3-B {ECO:0000303|PubMed:24616101};
CC IsoId=S4R2P9-2; Sequence=VSP_057981;
CC -!- TISSUE SPECIFICITY: Detected in gray and white matter in the spinal
CC cord (PubMed:21959935). Detected in hippocampus neurons
CC (PubMed:21593315). Detected in brain cortex neurons (PubMed:24101730).
CC Detected in skeletal muscle (at protein level) (PubMed:14722618).
CC Isoform 1 and isoform 2 are highly expressed in brain; levels are
CC higher for isoform 2 (PubMed:24616101). Isoform 1 and isoform 2 are
CC detected in soleus muscle; levels are higher for isoform 1
CC (PubMed:24616101). Detected in gastrocnemius muscle (PubMed:14722618).
CC {ECO:0000269|PubMed:14722618, ECO:0000269|PubMed:21593315,
CC ECO:0000269|PubMed:21959935, ECO:0000269|PubMed:24101730,
CC ECO:0000269|PubMed:24616101}.
CC -!- INDUCTION: Down-regulated by hypoxia combined with glucose deprivation
CC (at protein level). {ECO:0000269|PubMed:24101730}.
CC -!- DOMAIN: The cytoplasmic Calx-beta domains bind the regulatory Ca(2+).
CC The first Calx-beta domain can bind up to four Ca(2+) ions. The second
CC domain can bind another two Ca(2+) ions that are essential for calcium-
CC regulated ion exchange. {ECO:0000250|UniProtKB:P23685}.
CC -!- DISRUPTION PHENOTYPE: Mice appear grossly normal, are viable and
CC fertile, but display muscle fiber necrosis; this affects less than 10%
CC of all fibers. Muscle fibers from flexor digitorum brevis show lack of
CC calcium exchange activity, and very slow return of cytoplasmic Ca(2+)
CC to baseline levels after stimulation with caffeine, a stimulus that
CC triggers release of Ca(2+) stores from the sarcoplasmic reticulum.
CC Mutant mice display decreased endurance and perform poorly on the rota-
CC rod test or when hanging from a taut wire, indicating poor coordination
CC and increased fatigue (PubMed:14722618). Mutant mice display increased
CC cytoplasmic Ca(2+) levels and increased delays in the decrease of
CC cytoplasmic Ca(2+) back to baseline levels after stimulation of
CC hippocampus neurons (PubMed:21593315). They show impaired synaptic
CC transmisison, impaired long-term potentiation, impaired learning and
CC memory (PubMed:21593315). Besides, mutant mice display a decreased size
CC of the spinal cord, decreased myelination, decreased numbers of
CC oligodendrocytes and increased numbers of oligodendrocyte precursor
CC cells (PubMed:21959935). {ECO:0000269|PubMed:14722618,
CC ECO:0000269|PubMed:21959935}.
CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC family. SLC8 subfamily. {ECO:0000305}.
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DR EMBL; AF453257; AAL39160.1; -; mRNA.
DR EMBL; AK165197; BAE38073.1; -; mRNA.
DR EMBL; AC124384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC052435; AAH52435.1; -; mRNA.
DR EMBL; BC080862; AAH80862.1; -; mRNA.
DR CCDS; CCDS36485.1; -. [S4R2P9-1]
DR CCDS; CCDS49103.1; -. [S4R2P9-2]
DR RefSeq; NP_001161392.1; NM_001167920.1. [S4R2P9-2]
DR RefSeq; NP_536688.2; NM_080440.3. [S4R2P9-1]
DR PDB; 2LT9; NMR; -; A=528-682.
DR PDBsum; 2LT9; -.
DR AlphaFoldDB; S4R2P9; -.
DR SMR; S4R2P9; -.
DR STRING; 10090.ENSMUSP00000138735; -.
DR GlyGen; S4R2P9; 2 sites.
DR iPTMnet; S4R2P9; -.
DR PhosphoSitePlus; S4R2P9; -.
DR MaxQB; S4R2P9; -.
DR PaxDb; S4R2P9; -.
DR PRIDE; S4R2P9; -.
DR ProteomicsDB; 286143; -. [S4R2P9-1]
DR ProteomicsDB; 286144; -. [S4R2P9-2]
DR Antibodypedia; 12397; 166 antibodies from 24 providers.
DR DNASU; 110893; -.
DR Ensembl; ENSMUST00000085238; ENSMUSP00000082334; ENSMUSG00000079055. [S4R2P9-2]
DR Ensembl; ENSMUST00000182208; ENSMUSP00000138735; ENSMUSG00000079055. [S4R2P9-1]
DR GeneID; 110893; -.
DR KEGG; mmu:110893; -.
DR UCSC; uc007obv.2; mouse. [S4R2P9-1]
DR UCSC; uc007obw.2; mouse.
DR CTD; 6547; -.
DR MGI; MGI:107976; Slc8a3.
DR VEuPathDB; HostDB:ENSMUSG00000079055; -.
DR eggNOG; KOG1306; Eukaryota.
DR GeneTree; ENSGT00940000157547; -.
DR OMA; VEMANYH; -.
DR PhylomeDB; S4R2P9; -.
DR Reactome; R-MMU-418359; Reduction of cytosolic Ca++ levels.
DR Reactome; R-MMU-425561; Sodium/Calcium exchangers.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR BioGRID-ORCS; 110893; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Slc8a3; mouse.
DR PRO; PR:S4R2P9; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; S4R2P9; protein.
DR Bgee; ENSMUSG00000079055; Expressed in bone fossa and 164 other tissues.
DR ExpressionAtlas; S4R2P9; baseline and differential.
DR Genevisible; Q8VHJ8; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; IMP:ARUK-UCL.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0031594; C:neuromuscular junction; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098794; C:postsynapse; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IMP:ARUK-UCL.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0016528; C:sarcoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:ARUK-UCL.
DR GO; GO:0015368; F:calcium:cation antiporter activity; IDA:MGI.
DR GO; GO:1905060; F:calcium:cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0005432; F:calcium:sodium antiporter activity; IMP:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0015491; F:cation:cation antiporter activity; IBA:GO_Central.
DR GO; GO:0099580; F:ion antiporter activity involved in regulation of postsynaptic membrane potential; IMP:SynGO.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990034; P:calcium ion export across plasma membrane; ISO:MGI.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISO:MGI.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:MGI.
DR GO; GO:0007612; P:learning; IMP:UniProtKB.
DR GO; GO:0007611; P:learning or memory; IMP:ARUK-UCL.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:UniProtKB.
DR GO; GO:0007613; P:memory; IMP:UniProtKB.
DR GO; GO:0030001; P:metal ion transport; IDA:MGI.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0098815; P:modulation of excitatory postsynaptic potential; IMP:ARUK-UCL.
DR GO; GO:0042552; P:myelination; IMP:UniProtKB.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IMP:ARUK-UCL.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0014819; P:regulation of skeletal muscle contraction; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; ISO:MGI.
DR GO; GO:0050808; P:synapse organization; IMP:ARUK-UCL.
DR Gene3D; 1.20.1420.30; -; 2.
DR Gene3D; 2.60.40.2030; -; 2.
DR InterPro; IPR038081; CalX-like_sf.
DR InterPro; IPR003644; Calx_beta.
DR InterPro; IPR004836; Na_Ca_Ex.
DR InterPro; IPR032452; Na_Ca_Ex_C-exten.
DR InterPro; IPR004837; NaCa_Exmemb.
DR InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR Pfam; PF03160; Calx-beta; 2.
DR Pfam; PF01699; Na_Ca_ex; 2.
DR Pfam; PF16494; Na_Ca_ex_C; 1.
DR PRINTS; PR01259; NACAEXCHNGR.
DR SMART; SM00237; Calx_beta; 2.
DR SUPFAM; SSF141072; SSF141072; 2.
DR TIGRFAMs; TIGR00845; caca; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antiport; Calcium; Calcium transport;
KW Calmodulin-binding; Cell junction; Cell membrane; Cell projection;
KW Cytoplasm; Endoplasmic reticulum; Glycoprotein; Ion transport; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion outer membrane;
KW Reference proteome; Repeat; Signal; Sodium; Sodium transport; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..928
FT /note="Sodium/calcium exchanger 3"
FT /id="PRO_0000434797"
FT TOPO_DOM 31..73
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 95..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..201
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..230
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 231..251
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 252..727
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 728..748
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 749..755
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 756..776
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 777..779
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 780..800
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 801..829
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 830..850
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 851..861
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 862..882
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 883..904
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 905..925
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 926..928
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 390..485
FT /note="Calx-beta 1"
FT /evidence="ECO:0000255"
FT DOMAIN 519..618
FT /note="Calx-beta 2"
FT /evidence="ECO:0000255"
FT REGION 253..272
FT /note="Putative calmodulin-binding region"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 445
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 445
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 473
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 525
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 526
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 527
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 527
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 543
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 579
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 605
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 605
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT BINDING 673
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:P23685"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 824
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 599..636
FT /note="HIKVIDDKAYEKNKNYVIEMMGPRMVDMSVQKALLLSP -> RVKIVDEEEY
FT ERQENFFIALGEPKWMERGIS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_057981"
FT CONFLICT 754
FT /note="H -> P (in Ref. 1; AAL39160)"
FT /evidence="ECO:0000305"
FT STRAND 532..535
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 537..541
FT /evidence="ECO:0007829|PDB:2LT9"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 546..554
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 562..573
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 578..580
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 585..589
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 595..602
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 612..618
FT /evidence="ECO:0007829|PDB:2LT9"
FT TURN 624..626
FT /evidence="ECO:0007829|PDB:2LT9"
FT HELIX 645..656
FT /evidence="ECO:0007829|PDB:2LT9"
FT STRAND 666..674
FT /evidence="ECO:0007829|PDB:2LT9"
SQ SEQUENCE 928 AA; 102984 MW; 748C4E947C1A43A1 CRC64;
MAWLRLQPLT SAFLHFGLVT FVLFLNCLRA EAGDSGDVPS AGQNNESCSG SSDCKEGVIL
PIWYPENPSL GDKIARVIVY FVALIYMFLG VSIIADRFMA SIEVITSQER EVTIKKPNGE
TSTTTIRVWN ETVSNLTLMA LGSSAPEILL SLIEVCGHGF IAGDLGPSTI VGSAAFNMFI
IIGICVYVIP DGETRKIKHL RVFFVTAAWS IFAYIWLYMI LAVFSPGVVQ VWEGLLTLFF
FPVCVLLAWV ADKRLLFYKY MHKKYRTDKH RGIIIETEGD HPKGIEMDGK MMNSHFLDGN
FTPLEGKEVD ESRREMIRIL KDLKQKHPEK DLDQLVEMAN YYALSHQQKS RAFYRIQATR
MMTGAGNILK KHAAEQAKKT SSMSEVHTDE PEDFASKVFF DPCSYQCLEN CGAVLLTVVR
KGGDISKTMY VDYKTEDGSA NAGADYEFTE GTVVLKPGET QKEFSVGIID DDIFEEDEHF
FVRLSNVRVE EEQLAEGMLP AILNSLPLPR AVLASPCVAT VTILDDDHAG IFTFECDTIH
VSESIGVMEV KVLRTSGARG TVIVPFRTVE GTAKGGGEDF EDAYGELEFK NDETVKTIHI
KVIDDKAYEK NKNYVIEMMG PRMVDMSVQK ALLLSPEVTD RKLTVEEEEA KRIAEMGKPV
LGEHPKLEVI IEESYEFKST VDKLIKKTNL ALVVGTHSWR DQFMEAITVS AGGDEDEDES
GEERLPSCFD YVMHFLTVFW KVLFACVPPT EYCHGWACFV VSILIIGMLT AIIGDLASHF
GCTIGLKDSV TAVVFVAFGT SVPDTFASKA AALQDVYADA SIGNVTGSNA VNVFLGIGLA
WSVAAIYWAM QGQEFHVSAG TLAFSVTLFT IFAFVCLSVL LYRRRPHLGG ELGGPRGCKL
ATTWLFVSLW LLYILFATLE AYCYIKGF
