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Database: UniProt
Entry: NAC3_HUMAN
LinkDB: NAC3_HUMAN
Original site: NAC3_HUMAN 
ID   NAC3_HUMAN              Reviewed;         927 AA.
AC   P57103; Q5K3P6; Q5K3P7; Q8IUE9; Q8IUF0; Q8NFI7; Q96QG1; Q96QG2;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   29-AUG-2003, sequence version 2.
DT   27-MAR-2024, entry version 182.
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; Synonyms=NCX3;
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] (ISOFORMS 2; 3; 4; 7 AND 8).
RX   PubMed=12406570; DOI=10.1016/s0378-1119(02)00982-4;
RA   Gabellini N., Bortoluzzi S., Danieli G.A., Carafoli E.;
RT   "The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3
RT   isoforms.";
RL   Gene 298:1-7(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
RX   PubMed=12558991; DOI=10.1046/j.1471-4159.2003.01511.x;
RA   Gabellini N., Bortoluzzi S., Danieli G.A., Carafoli E.;
RT   "Control of the Na+/Ca2+ exchanger 3 promoter by cyclic adenosine
RT   monophosphate and Ca2+ in differentiating neurons.";
RL   J. Neurochem. 84:282-293(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6), AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=15777725; DOI=10.1016/j.gene.2005.01.003;
RA   Lindgren R.M., Zhao J., Heller S., Berglind H., Nister M.;
RT   "Molecular cloning and characterization of two novel truncated isoforms of
RT   human Na+/Ca2+ exchanger 3, expressed in fetal brain.";
RL   Gene 348:143-155(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
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 1-595.
RA   Kraev A.S., Chumakov I.M., Carafoli E.;
RT   "The organization of the human gene of the sodium-calcium exchanger.";
RL   Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
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   [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   VARIANT [LARGE SCALE ANALYSIS] GLN-612.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
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. In a first phase, voltage-gated
CC       channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to
CC       release of Ca(2+) stores from the endoplasmic reticulum. SLC8A3
CC       mediates the export of Ca(2+) from the cell during the next phase, so
CC       that cytoplasmic Ca(2+) levels rapidly return to baseline. Contributes
CC       to Ca(2+) transport during excitation-contraction coupling in muscle.
CC       In neurons, contributes to the rapid decrease of cytoplasmic Ca(2+)
CC       levels back to baseline after neuronal activation, and thereby
CC       contributes to modulate synaptic plasticity, learning and memory (By
CC       similarity). Required for normal oligodendrocyte differentiation and
CC       for normal myelination (PubMed:21959935). Mediates Ca(2+) efflux from
CC       mitochondria and contributes to mitochondrial Ca(2+) ion homeostasis
CC       (By similarity). {ECO:0000250|UniProtKB:S4R2P9,
CC       ECO:0000269|PubMed:21959935}.
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:0000250|UniProtKB:S4R2P9};
CC   -!- ACTIVITY REGULATION: Calcium transport is down-regulated by Na(+) and
CC       stimulated by Ca(2+). {ECO:0000250|UniProtKB:P70549}.
CC   -!- SUBUNIT: Interacts with AKAP1. {ECO:0000250|UniProtKB:S4R2P9}.
CC   -!- INTERACTION:
CC       P57103-7; P48165: GJA8; NbExp=3; IntAct=EBI-17459901, EBI-17458373;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21959935};
CC       Multi-pass membrane protein {ECO:0000305}. Perikaryon
CC       {ECO:0000250|UniProtKB:P70549}. Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:P70549}. Cell projection, dendritic spine
CC       {ECO:0000250|UniProtKB:P70549}. Cell membrane, sarcolemma
CC       {ECO:0000250|UniProtKB:S4R2P9}. Cytoplasm, sarcoplasm
CC       {ECO:0000250|UniProtKB:S4R2P9}. Cell junction
CC       {ECO:0000250|UniProtKB:S4R2P9}. Mitochondrion outer membrane
CC       {ECO:0000250|UniProtKB:S4R2P9}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:S4R2P9}. Cytoplasm, perinuclear region
CC       {ECO:0000269|PubMed:21959935}. Endoplasmic reticulum membrane
CC       {ECO:0000305|PubMed:21959935}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:S4R2P9}. Note=Detected at neuromuscular
CC       junctions. {ECO:0000250|UniProtKB:S4R2P9}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=7;
CC       Name=3; Synonyms=NCX3.3;
CC         IsoId=P57103-1; Sequence=Displayed;
CC       Name=2; Synonyms=NCX3.2;
CC         IsoId=P57103-2; Sequence=VSP_008116;
CC       Name=4; Synonyms=NCX3.4;
CC         IsoId=P57103-3; Sequence=VSP_008117, VSP_008118;
CC       Name=5; Synonyms=NCX3-tN.1;
CC         IsoId=P57103-4; Sequence=VSP_043125;
CC       Name=6; Synonyms=NCX3-tN.2;
CC         IsoId=P57103-5; Sequence=VSP_043126, VSP_008116;
CC       Name=7;
CC         IsoId=P57103-6; Sequence=VSP_043850;
CC       Name=8;
CC         IsoId=P57103-7; Sequence=VSP_044502;
CC   -!- TISSUE SPECIFICITY: Isoform 2 is expressed in brain and skeletal
CC       muscle. Isoform 3 is expressed in excitable cells of brain, retina and
CC       skeletal muscle. Isoform 4 is expressed in skeletal muscle.
CC       {ECO:0000269|PubMed:15777725}.
CC   -!- DEVELOPMENTAL STAGE: Up-regulated during in vitro differentiation of
CC       oligodendrocytes (at protein level). Up-regulated during in vitro
CC       differentiation of oligodendrocytes. {ECO:0000269|PubMed:21959935}.
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   -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 5]: Expressed in fetal brain. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 6]: Expressed in fetal brain. {ECO:0000305}.
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; AF510501; AAN60790.1; -; mRNA.
DR   EMBL; AF510502; AAN60791.1; -; mRNA.
DR   EMBL; AF510503; AAN60792.1; -; mRNA.
DR   EMBL; AF508982; AAM90955.1; -; Genomic_DNA.
DR   EMBL; AJ304852; CAC40984.1; -; mRNA.
DR   EMBL; AJ304853; CAC40985.1; -; mRNA.
DR   EMBL; AJ745101; CAG33739.1; -; mRNA.
DR   EMBL; AJ745102; CAG33740.1; -; mRNA.
DR   EMBL; AL135747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL160191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471061; EAW81019.1; -; Genomic_DNA.
DR   EMBL; CH471061; EAW81021.1; -; Genomic_DNA.
DR   EMBL; CH471061; EAW81026.1; -; Genomic_DNA.
DR   EMBL; BC142969; AAI42970.1; -; mRNA.
DR   EMBL; X93017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS35498.1; -. [P57103-1]
DR   CCDS; CCDS41967.1; -. [P57103-4]
DR   CCDS; CCDS45131.1; -. [P57103-5]
DR   CCDS; CCDS53904.1; -. [P57103-6]
DR   CCDS; CCDS9799.1; -. [P57103-7]
DR   CCDS; CCDS9800.1; -. [P57103-2]
DR   RefSeq; NP_001123889.1; NM_001130417.2. [P57103-5]
DR   RefSeq; NP_150287.1; NM_033262.4. [P57103-7]
DR   RefSeq; NP_489479.1; NM_058240.3. [P57103-6]
DR   RefSeq; NP_891977.1; NM_182932.2. [P57103-2]
DR   RefSeq; NP_891981.1; NM_182936.2. [P57103-4]
DR   RefSeq; NP_892114.1; NM_183002.2. [P57103-1]
DR   RefSeq; XP_016877095.1; XM_017021606.1. [P57103-1]
DR   RefSeq; XP_016877097.1; XM_017021608.1. [P57103-2]
DR   AlphaFoldDB; P57103; -.
DR   SMR; P57103; -.
DR   BioGRID; 112437; 12.
DR   IntAct; P57103; 7.
DR   MINT; P57103; -.
DR   STRING; 9606.ENSP00000370669; -.
DR   GuidetoPHARMACOLOGY; 947; -.
DR   TCDB; 2.A.19.3.3; the ca(2+):cation antiporter (caca) family.
DR   GlyCosmos; P57103; 2 sites, No reported glycans.
DR   GlyGen; P57103; 3 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P57103; -.
DR   PhosphoSitePlus; P57103; -.
DR   BioMuta; SLC8A3; -.
DR   DMDM; 34395973; -.
DR   EPD; P57103; -.
DR   MassIVE; P57103; -.
DR   PaxDb; 9606-ENSP00000370669; -.
DR   PeptideAtlas; P57103; -.
DR   ProteomicsDB; 56998; -. [P57103-1]
DR   ProteomicsDB; 56999; -. [P57103-2]
DR   ProteomicsDB; 57000; -. [P57103-3]
DR   ProteomicsDB; 57002; -. [P57103-5]
DR   ProteomicsDB; 57003; -. [P57103-6]
DR   ProteomicsDB; 77876; -.
DR   TopDownProteomics; P57103-2; -. [P57103-2]
DR   Antibodypedia; 12397; 190 antibodies from 24 providers.
DR   DNASU; 6547; -.
DR   Ensembl; ENST00000216568.11; ENSP00000216568.7; ENSG00000100678.20. [P57103-5]
DR   Ensembl; ENST00000356921.7; ENSP00000349392.3; ENSG00000100678.20. [P57103-2]
DR   Ensembl; ENST00000381269.6; ENSP00000370669.2; ENSG00000100678.20. [P57103-1]
DR   Ensembl; ENST00000394330.6; ENSP00000377863.2; ENSG00000100678.20. [P57103-4]
DR   Ensembl; ENST00000494208.5; ENSP00000436332.1; ENSG00000100678.20. [P57103-3]
DR   Ensembl; ENST00000528359.6; ENSP00000433531.1; ENSG00000100678.20. [P57103-7]
DR   Ensembl; ENST00000534137.5; ENSP00000436688.1; ENSG00000100678.20. [P57103-6]
DR   Ensembl; ENST00000705391.1; ENSP00000516120.1; ENSG00000100678.20. [P57103-2]
DR   GeneID; 6547; -.
DR   KEGG; hsa:6547; -.
DR   MANE-Select; ENST00000356921.7; ENSP00000349392.3; NM_182932.3; NP_891977.1. [P57103-2]
DR   UCSC; uc001xlu.5; human. [P57103-1]
DR   AGR; HGNC:11070; -.
DR   CTD; 6547; -.
DR   DisGeNET; 6547; -.
DR   GeneCards; SLC8A3; -.
DR   HGNC; HGNC:11070; SLC8A3.
DR   HPA; ENSG00000100678; Group enriched (brain, retina, skeletal muscle, tongue).
DR   MIM; 607991; gene.
DR   neXtProt; NX_P57103; -.
DR   OpenTargets; ENSG00000100678; -.
DR   PharmGKB; PA315; -.
DR   VEuPathDB; HostDB:ENSG00000100678; -.
DR   eggNOG; KOG1306; Eukaryota.
DR   GeneTree; ENSGT00940000157547; -.
DR   HOGENOM; CLU_012872_0_1_1; -.
DR   InParanoid; P57103; -.
DR   OMA; VEMANYH; -.
DR   OrthoDB; 462435at2759; -.
DR   PhylomeDB; P57103; -.
DR   TreeFam; TF314308; -.
DR   PathwayCommons; P57103; -.
DR   Reactome; R-HSA-418359; Reduction of cytosolic Ca++ levels.
DR   Reactome; R-HSA-425561; Sodium/Calcium exchangers.
DR   Reactome; R-HSA-5578775; Ion homeostasis.
DR   Reactome; R-HSA-8949215; Mitochondrial calcium ion transport.
DR   SignaLink; P57103; -.
DR   BioGRID-ORCS; 6547; 7 hits in 1147 CRISPR screens.
DR   ChiTaRS; SLC8A3; human.
DR   GenomeRNAi; 6547; -.
DR   Pharos; P57103; Tchem.
DR   PRO; PR:P57103; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; P57103; Protein.
DR   Bgee; ENSG00000100678; Expressed in tibia and 125 other cell types or tissues.
DR   ExpressionAtlas; P57103; baseline and differential.
DR   Genevisible; P57103; HS.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR   GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR   GO; GO:0043679; C:axon terminus; ISS:ARUK-UCL.
DR   GO; GO:0030425; C:dendrite; ISS:ARUK-UCL.
DR   GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR   GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0098794; C:postsynapse; IBA:GO_Central.
DR   GO; GO:0014069; C:postsynaptic density; ISS:ARUK-UCL.
DR   GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR   GO; GO:0016528; C:sarcoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IDA:ARUK-UCL.
DR   GO; GO:0005432; F:calcium:sodium antiporter activity; ISS:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0099580; F:monoatomic ion antiporter activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
DR   GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0007154; P:cell communication; IEA:InterPro.
DR   GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR   GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; ISS:UniProtKB.
DR   GO; GO:0007612; P:learning; ISS:UniProtKB.
DR   GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL.
DR   GO; GO:0060291; P:long-term synaptic potentiation; ISS:UniProtKB.
DR   GO; GO:0007613; P:memory; ISS:UniProtKB.
DR   GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISS:UniProtKB.
DR   GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0098815; P:modulation of excitatory postsynaptic potential; ISS:ARUK-UCL.
DR   GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome.
DR   GO; GO:0042552; P:myelination; ISS:UniProtKB.
DR   GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; ISS:ARUK-UCL.
DR   GO; GO:0048709; P:oligodendrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR   GO; GO:0014819; P:regulation of skeletal muscle contraction; ISS:UniProtKB.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0050808; P:synapse organization; ISS:ARUK-UCL.
DR   Gene3D; 2.60.40.2030; -; 2.
DR   Gene3D; 1.20.1420.30; NCX, central ion-binding region; 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   NCBIfam; TIGR00845; caca; 1.
DR   PANTHER; PTHR11878; SODIUM/CALCIUM EXCHANGER; 1.
DR   PANTHER; PTHR11878:SF7; SODIUM_CALCIUM EXCHANGER 3; 1.
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; CalX-like; 2.
PE   1: Evidence at protein level;
KW   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..927
FT                   /note="Sodium/calcium exchanger 3"
FT                   /id="PRO_0000019384"
FT   TOPO_DOM        31..73
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        74..94
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        95..147
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        148..168
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        169
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        170..190
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        191..202
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        203..223
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        224..230
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        231..251
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        252..726
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        727..747
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        748..754
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        755..775
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        776..778
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        779..799
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        800..828
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        829..849
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        850..860
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        861..881
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        882..903
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        904..924
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        925..927
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          140..180
FT                   /note="Alpha-1"
FT   DOMAIN          386..485
FT                   /note="Calx-beta 1"
FT   DOMAIN          519..619
FT                   /note="Calx-beta 2"
FT   REPEAT          796..832
FT                   /note="Alpha-2"
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         606
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000250|UniProtKB:P23685"
FT   BINDING         607
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000250|UniProtKB:P23685"
FT   BINDING         607
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000250|UniProtKB:P23685"
FT   BINDING         672
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"
FT   CARBOHYD        823
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..643
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:15777725"
FT                   /id="VSP_043125"
FT   VAR_SEQ         1..623
FT                   /note="Missing (in isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:15777725"
FT                   /id="VSP_043126"
FT   VAR_SEQ         596..620
FT                   /note="KTIRVKIVDEEEYERQENFFIALGE -> CDRQEADYGRRGGQEDSRDGKAS
FT                   IG (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12406570"
FT                   /id="VSP_008117"
FT   VAR_SEQ         599..638
FT                   /note="RVKIVDEEEYERQENFFIALGEPKWMERGISALLLSPDVT -> HIKVIDDE
FT                   AYEKNKNYFIEMMGPRMVDMSFQKALLLSP (in isoform 8)"
FT                   /evidence="ECO:0000303|PubMed:12406570"
FT                   /id="VSP_044502"
FT   VAR_SEQ         621..927
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12406570"
FT                   /id="VSP_008118"
FT   VAR_SEQ         630..635
FT                   /note="Missing (in isoform 2 and isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:12406570,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:15777725"
FT                   /id="VSP_008116"
FT   VAR_SEQ         636..638
FT                   /note="Missing (in isoform 7)"
FT                   /evidence="ECO:0000303|PubMed:12406570"
FT                   /id="VSP_043850"
FT   VARIANT         612
FT                   /note="E -> Q (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036463"
SQ   SEQUENCE   927 AA;  103010 MW;  7B43CB6A9D77615E CRC64;
     MAWLRLQPLT SAFLHFGLVT FVLFLNGLRA EAGGSGDVPS TGQNNESCSG SSDCKEGVIL
     PIWYPENPSL GDKIARVIVY FVALIYMFLG VSIIADRFMA SIEVITSQER EVTIKKPNGE
     TSTTTIRVWN ETVSNLTLMA LGSSAPEILL SLIEVCGHGF IAGDLGPSTI VGSAAFNMFI
     IIGICVYVIP DGETRKIKHL RVFFITAAWS IFAYIWLYMI LAVFSPGVVQ VWEGLLTLFF
     FPVCVLLAWV ADKRLLFYKY MHKKYRTDKH RGIIIETEGD HPKGIEMDGK MMNSHFLDGN
     LVPLEGKEVD ESRREMIRIL KDLKQKHPEK DLDQLVEMAN YYALSHQQKS RAFYRIQATR
     MMTGAGNILK KHAAEQAKKA SSMSEVHTDE PEDFISKVFF DPCSYQCLEN CGAVLLTVVR
     KGGDMSKTMY VDYKTEDGSA NAGADYEFTE GTVVLKPGET QKEFSVGIID DDIFEEDEHF
     FVRLSNVRIE EEQPEEGMPP AIFNSLPLPR AVLASPCVAT VTILDDDHAG IFTFECDTIH
     VSESIGVMEV KVLRTSGARG TVIVPFRTVE GTAKGGGEDF EDTYGELEFK NDETVKTIRV
     KIVDEEEYER QENFFIALGE PKWMERGISA LLLSPDVTDR KLTMEEEEAK RIAEMGKPVL
     GEHPKLEVII EESYEFKTTV DKLIKKTNLA LVVGTHSWRD QFMEAITVSA AGDEDEDESG
     EERLPSCFDY VMHFLTVFWK VLFACVPPTE YCHGWACFAV SILIIGMLTA IIGDLASHFG
     CTIGLKDSVT AVVFVAFGTS VPDTFASKAA ALQDVYADAS IGNVTGSNAV NVFLGIGLAW
     SVAAIYWALQ GQEFHVSAGT LAFSVTLFTI FAFVCISVLL YRRRPHLGGE LGGPRGCKLA
     TTWLFVSLWL LYILFATLEA YCYIKGF
//
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