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 03-AUG-2022, entry version 173.
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 GlyGen; P57103; 2 sites.
DR iPTMnet; P57103; -.
DR PhosphoSitePlus; P57103; -.
DR BioMuta; SLC8A3; -.
DR DMDM; 34395973; -.
DR EPD; P57103; -.
DR MassIVE; P57103; -.
DR PaxDb; P57103; -.
DR PeptideAtlas; P57103; -.
DR PRIDE; P57103; -.
DR ProteomicsDB; 56998; -. [P57103-1]
DR ProteomicsDB; 56999; -. [P57103-2]
DR ProteomicsDB; 57002; -. [P57103-5]
DR ProteomicsDB; 57003; -. [P57103-6]
DR ProteomicsDB; 77876; -.
DR TopDownProteomics; P57103-2; -. [P57103-2]
DR Antibodypedia; 12397; 166 antibodies from 24 providers.
DR DNASU; 6547; -.
DR Ensembl; ENST00000216568.11; ENSP00000216568.7; ENSG00000100678.19. [P57103-5]
DR Ensembl; ENST00000356921.7; ENSP00000349392.3; ENSG00000100678.19. [P57103-2]
DR Ensembl; ENST00000357887.7; ENSP00000350560.3; ENSG00000100678.19. [P57103-7]
DR Ensembl; ENST00000381269.6; ENSP00000370669.2; ENSG00000100678.19. [P57103-1]
DR Ensembl; ENST00000394330.6; ENSP00000377863.2; ENSG00000100678.19. [P57103-4]
DR Ensembl; ENST00000494208.5; ENSP00000436332.1; ENSG00000100678.19. [P57103-3]
DR Ensembl; ENST00000528359.5; ENSP00000433531.1; ENSG00000100678.19. [P57103-7]
DR Ensembl; ENST00000534137.5; ENSP00000436688.1; ENSG00000100678.19. [P57103-6]
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 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; 490546at2759; -.
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; 5 hits in 1068 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 124 other 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:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
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; TAS:Reactome.
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:0015491; F:cation:cation antiporter activity; IBA:GO_Central.
DR GO; GO:0099580; F:ion antiporter activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0006874; P:cellular calcium ion homeostasis; ISS:UniProtKB.
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:0006811; P:ion transport; TAS:Reactome.
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:0030001; P:metal ion transport; IBA:GO_Central.
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: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; 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 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
