ID NAC1_HUMAN Reviewed; 973 AA. AC P32418; A8K6N1; D6W595; O95849; Q4QQG6; Q587I6; Q59GN4; Q9UBL8; Q9UD55; AC Q9UDN1; Q9UDN2; Q9UKX6; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 3. DT 27-MAR-2024, entry version 213. DE RecName: Full=Sodium/calcium exchanger 1; DE AltName: Full=Na(+)/Ca(2+)-exchange protein 1; DE AltName: Full=Solute carrier family 8 member 1; DE Flags: Precursor; GN Name=SLC8A1; GN Synonyms=CNC, NCX1 {ECO:0000303|PubMed:11241183, GN ECO:0000303|PubMed:23376057}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Heart; RX PubMed=1374913; DOI=10.1073/pnas.89.10.4769; RA Komuro I., Wenninger K.E., Philipson K.D., Izumo S.; RT "Molecular cloning and characterization of the human cardiac Na+/Ca2+ RT exchanger cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 89:4769-4773(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 7), FUNCTION, TRANSPORTER RP ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=11241183; DOI=10.1677/joe.0.1680517; RA Van Eylen F., Bollen A., Herchuelz A.; RT "NCX1 Na/Ca exchanger splice variants in pancreatic islet cells."; RL J. Endocrinol. 168:517-526(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7). RA Mangini N.J., Chen W., Wang Q., Kennedy B.G.; RT "Na+/Ca2+ exchanger isoforms in cultured human retinal pigment RT epithelium."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Placenta; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 459-681 (ISOFORM 10). RX PubMed=10908415; DOI=10.1007/s00223001098; RA Lundquist P., Lundgren T., Gritli-Linde A., Linde A.; RT "Na+/Ca2+ exchanger isoforms of rat odontoblasts and osteoblasts."; RL Calcif. Tissue Int. 67:60-67(2000). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 558-973 (ISOFORM 5). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 594-973 (ISOFORM 5). 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 [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 600-684 (ISOFORM 3). RC TISSUE=Embryonic kidney; RX PubMed=8048567; DOI=10.1152/ajprenal.1994.267.1.f70; RA Loo T.W., Clarke D.M.; RT "Functional expression of human renal Na+/Ca2+ exchanger in insect cells."; RL Am. J. Physiol. 267:F70-F74(1994). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=1476165; DOI=10.1152/ajpcell.1992.263.6.c1241; RA Kofuji P., Hadley R.W., Kieval R.S., Lederer W.J., Schulze D.H.; RT "Expression of the Na-Ca exchanger in diverse tissues: a study using the RT cloned human cardiac Na-Ca exchanger."; RL Am. J. Physiol. 263:C1241-C1249(1992). RN [12] RP TOPOLOGY. RX PubMed=23376057; DOI=10.1016/j.yjmcc.2013.01.010; RA Ren X., Philipson K.D.; RT "The topology of the cardiac Na(+)/Ca(2)(+) exchanger, NCX1."; RL J. Mol. Cell. Cardiol. 57:68-71(2013). RN [13] 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). CC -!- FUNCTION: Mediates the exchange of one Ca(2+) ion against three to four CC Na(+) ions across the cell membrane, and thereby contributes to the CC regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular CC processes (PubMed:1374913, PubMed:11241183, PubMed:1476165). CC Contributes to Ca(2+) transport during excitation-contraction coupling CC in muscle (PubMed:1374913, PubMed:11241183, PubMed:1476165). In a first CC phase, voltage-gated channels mediate the rapid increase of cytoplasmic CC Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic CC reticulum (PubMed:1374913, PubMed:11241183, PubMed:1476165). SLC8A1 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 CC (PubMed:1374913, PubMed:11241183, PubMed:1476165). Required for normal CC embryonic heart development and the onset of heart contractions (By CC similarity). {ECO:0000250|UniProtKB:P70414, CC ECO:0000269|PubMed:11241183, ECO:0000269|PubMed:1374913, CC ECO:0000269|PubMed:1476165}. 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:0000269|PubMed:11241183, ECO:0000269|PubMed:1374913}; CC -!- ACTIVITY REGULATION: Activated by micromolar levels of Ca(2+). CC {ECO:0000250|UniProtKB:Q01728}. CC -!- INTERACTION: CC P32418; Q01484-2: ANK2; NbExp=2; IntAct=EBI-2682189, EBI-941994; CC P32418; P23297: S100A1; NbExp=3; IntAct=EBI-2682189, EBI-743686; CC P32418; P33763: S100A5; NbExp=2; IntAct=EBI-2682189, EBI-7211732; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11241183, CC ECO:0000269|PubMed:1374913, ECO:0000269|PubMed:1476165}; Multi-pass CC membrane protein {ECO:0000269|PubMed:23376057}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=NaCa1, NCX1.1; CC IsoId=P32418-1; Sequence=Displayed; CC Name=3; Synonyms=NaCa3, NCX1.3; CC IsoId=P32418-2; Sequence=VSP_003397, VSP_003398, VSP_003400; CC Name=7; Synonyms=NaCa7, NCX1.7; CC IsoId=P32418-3; Sequence=VSP_003397, VSP_003398, VSP_003399; CC Name=10; Synonyms=NaCa10, NCX1.10; CC IsoId=P32418-4; Sequence=VSP_003397, VSP_003398; CC Name=5; CC IsoId=P32418-5; Sequence=VSP_003399; CC -!- TISSUE SPECIFICITY: Detected primarily in heart and at lower levels in CC brain (PubMed:1374913). Expressed in cardiac sarcolemma, brain, kidney, CC liver, pancreas, skeletal muscle, placenta and lung (PubMed:1476165). CC {ECO:0000269|PubMed:1374913, ECO:0000269|PubMed:1476165}. 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 -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) CC family. SLC8 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH98308.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M91368; AAA35702.1; -; mRNA. DR EMBL; AF108388; AAF08987.1; -; mRNA. DR EMBL; AF108389; AAF08988.1; -; mRNA. DR EMBL; AF128524; AAD26362.1; -; mRNA. DR EMBL; AK291696; BAF84385.1; -; mRNA. DR EMBL; AC007254; AAF19235.1; -; Genomic_DNA. DR EMBL; AC007281; AAF19237.1; -; Genomic_DNA. DR EMBL; AC007377; AAX81985.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00331.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00332.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00333.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00334.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00335.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00336.1; -; Genomic_DNA. DR EMBL; AF115505; AAD17213.1; -; mRNA. DR EMBL; AB209075; BAD92312.1; -; mRNA. DR EMBL; BC098308; AAH98308.1; ALT_INIT; mRNA. DR CCDS; CCDS1806.1; -. [P32418-1] DR CCDS; CCDS46264.1; -. [P32418-2] DR CCDS; CCDS46265.1; -. [P32418-5] DR CCDS; CCDS59430.1; -. [P32418-4] DR CCDS; CCDS92742.1; -. [P32418-3] DR PIR; S32815; S32815. DR RefSeq; NP_001106271.1; NM_001112800.1. [P32418-5] DR RefSeq; NP_001106272.1; NM_001112801.1. [P32418-3] DR RefSeq; NP_001106273.1; NM_001112802.1. [P32418-2] DR RefSeq; NP_001239553.1; NM_001252624.1. [P32418-4] DR RefSeq; NP_066920.1; NM_021097.2. [P32418-1] DR RefSeq; XP_005264571.1; XM_005264514.3. DR RefSeq; XP_006712144.1; XM_006712081.2. DR RefSeq; XP_006712145.1; XM_006712082.3. DR RefSeq; XP_006712146.1; XM_006712083.3. DR RefSeq; XP_006712147.1; XM_006712084.3. DR RefSeq; XP_006712148.1; XM_006712085.3. DR RefSeq; XP_011531356.1; XM_011533054.2. DR RefSeq; XP_011531357.1; XM_011533055.2. DR RefSeq; XP_011531358.1; XM_011533056.1. DR RefSeq; XP_016860235.1; XM_017004746.1. DR RefSeq; XP_016860237.1; XM_017004748.1. DR RefSeq; XP_016860238.1; XM_017004749.1. DR RefSeq; XP_016860239.1; XM_017004750.1. DR RefSeq; XP_016860240.1; XM_017004751.1. DR RefSeq; XP_016860241.1; XM_017004752.1. DR RefSeq; XP_016860242.1; XM_017004753.1. DR RefSeq; XP_016860243.1; XM_017004754.1. DR RefSeq; XP_016860247.1; XM_017004758.1. DR PDB; 8SGJ; EM; 3.10 A; A=1-973. DR PDB; 8SGT; EM; 3.60 A; A=1-973. DR PDBsum; 8SGJ; -. DR PDBsum; 8SGT; -. DR AlphaFoldDB; P32418; -. DR EMDB; EMD-40457; -. DR EMDB; EMD-40460; -. DR EMDB; EMD-40467; -. DR SMR; P32418; -. DR BioGRID; 112436; 5. DR DIP; DIP-48356N; -. DR ELM; P32418; -. DR IntAct; P32418; 21. DR STRING; 9606.ENSP00000384763; -. DR BindingDB; P32418; -. DR ChEMBL; CHEMBL4076; -. DR DrugBank; DB00132; alpha-Linolenic acid. DR DrugBank; DB11093; Calcium citrate. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR DrugBank; DB06231; Caldaret. DR DrugBank; DB04855; Dronedarone. DR DrugBank; DB00159; Icosapent. DR DrugBank; DB09498; Strontium chloride Sr-89. DR DrugCentral; P32418; -. DR TCDB; 2.A.19.3.4; the ca(2+):cation antiporter (caca) family. DR GlyCosmos; P32418; 2 sites, No reported glycans. DR GlyGen; P32418; 2 sites. DR iPTMnet; P32418; -. DR PhosphoSitePlus; P32418; -. DR SwissPalm; P32418; -. DR BioMuta; SLC8A1; -. DR DMDM; 12644210; -. DR EPD; P32418; -. DR jPOST; P32418; -. DR MassIVE; P32418; -. DR PaxDb; 9606-ENSP00000384763; -. DR PeptideAtlas; P32418; -. DR ProteomicsDB; 54873; -. [P32418-1] DR ProteomicsDB; 54874; -. [P32418-2] DR ProteomicsDB; 54875; -. [P32418-3] DR ProteomicsDB; 54876; -. [P32418-4] DR Antibodypedia; 29673; 268 antibodies from 32 providers. DR DNASU; 6546; -. DR Ensembl; ENST00000332839.9; ENSP00000332931.4; ENSG00000183023.19. [P32418-1] DR Ensembl; ENST00000402441.5; ENSP00000385188.1; ENSG00000183023.19. [P32418-2] DR Ensembl; ENST00000403092.5; ENSP00000384763.1; ENSG00000183023.19. [P32418-1] DR Ensembl; ENST00000405269.5; ENSP00000385535.1; ENSG00000183023.19. [P32418-2] DR Ensembl; ENST00000405901.7; ENSP00000385678.3; ENSG00000183023.19. [P32418-5] DR Ensembl; ENST00000406391.2; ENSP00000385811.2; ENSG00000183023.19. [P32418-2] DR Ensembl; ENST00000406785.7; ENSP00000383886.1; ENSG00000183023.19. [P32418-2] DR Ensembl; ENST00000408028.6; ENSP00000384908.2; ENSG00000183023.19. [P32418-4] DR Ensembl; ENST00000705604.1; ENSP00000516142.1; ENSG00000183023.19. [P32418-3] DR GeneID; 6546; -. DR KEGG; hsa:6546; -. DR MANE-Select; ENST00000332839.9; ENSP00000332931.4; NM_021097.5; NP_066920.1. DR UCSC; uc002rrx.4; human. [P32418-1] DR AGR; HGNC:11068; -. DR CTD; 6546; -. DR DisGeNET; 6546; -. DR GeneCards; SLC8A1; -. DR HGNC; HGNC:11068; SLC8A1. DR HPA; ENSG00000183023; Tissue enriched (heart). DR MIM; 182305; gene. DR neXtProt; NX_P32418; -. DR OpenTargets; ENSG00000183023; -. DR PharmGKB; PA314; -. DR VEuPathDB; HostDB:ENSG00000183023; -. DR eggNOG; KOG1306; Eukaryota. DR GeneTree; ENSGT00940000155129; -. DR HOGENOM; CLU_012872_1_0_1; -. DR InParanoid; P32418; -. DR OMA; GNATGEC; -. DR OrthoDB; 462435at2759; -. DR PhylomeDB; P32418; -. DR TreeFam; TF314308; -. DR PathwayCommons; P32418; -. 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 SignaLink; P32418; -. DR BioGRID-ORCS; 6546; 9 hits in 1163 CRISPR screens. DR ChiTaRS; SLC8A1; human. DR GenomeRNAi; 6546; -. DR Pharos; P32418; Tchem. DR PRO; PR:P32418; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P32418; Protein. DR Bgee; ENSG00000183023; Expressed in heart right ventricle and 180 other cell types or tissues. DR ExpressionAtlas; P32418; baseline and differential. DR GO; GO:0030424; C:axon; ISS:ARUK-UCL. DR GO; GO:0043679; C:axon terminus; ISS:ARUK-UCL. DR GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL. DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL. DR GO; GO:0014704; C:intercalated disc; ISS:BHF-UCL. DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. 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:BHF-UCL. DR GO; GO:0045202; C:synapse; IDA:ARUK-UCL. DR GO; GO:0030315; C:T-tubule; ISS:BHF-UCL. DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL. DR GO; GO:0030506; F:ankyrin binding; IPI:BHF-UCL. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0005432; F:calcium:sodium antiporter activity; IDA:BHF-UCL. DR GO; GO:0005516; F:calmodulin binding; IDA:ARUK-UCL. DR GO; GO:0008092; F:cytoskeletal protein binding; IDA:BHF-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL. DR GO; GO:1901660; P:calcium ion export; IDA:BHF-UCL. DR GO; GO:0055074; P:calcium ion homeostasis; ISS:BHF-UCL. DR GO; GO:0070509; P:calcium ion import; IDA:BHF-UCL. DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; TAS:BHF-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IGI:UniProtKB. DR GO; GO:0060402; P:calcium ion transport into cytosol; ISS:BHF-UCL. DR GO; GO:0055013; P:cardiac muscle cell development; ISS:BHF-UCL. DR GO; GO:0060048; P:cardiac muscle contraction; TAS:BHF-UCL. DR GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; ISS:BHF-UCL. DR GO; GO:0071313; P:cellular response to caffeine; ISS:BHF-UCL. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:BHF-UCL. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISS:ARUK-UCL. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; IDA:BHF-UCL. DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; TAS:BHF-UCL. DR GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome. DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc. DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISS:BHF-UCL. DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; ISS:ARUK-UCL. DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:UniProtKB. DR GO; GO:0098735; P:positive regulation of the force of heart contraction; IMP:BHF-UCL. DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome. DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; TAS:BHF-UCL. DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; ISS:BHF-UCL. DR GO; GO:0010649; P:regulation of cell communication by electrical coupling; TAS:BHF-UCL. DR GO; GO:0010468; P:regulation of gene expression; ISS:ARUK-UCL. DR GO; GO:0002027; P:regulation of heart rate; ISS:BHF-UCL. DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:BHF-UCL. DR GO; GO:0055119; P:relaxation of cardiac muscle; TAS:BHF-UCL. DR GO; GO:0044557; P:relaxation of smooth muscle; ISS:BHF-UCL. DR GO; GO:0035994; P:response to muscle stretch; IMP:BHF-UCL. DR GO; GO:0036376; P:sodium ion export across plasma membrane; IDA:BHF-UCL. DR GO; GO:0098719; P:sodium ion import across plasma membrane; IDA:BHF-UCL. DR GO; GO:0035725; P:sodium ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0014829; P:vascular associated smooth muscle contraction; ISS:BHF-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; IPR001623; DnaJ_domain. DR InterPro; IPR004836; Na_Ca_Ex. DR InterPro; IPR032452; Na_Ca_Ex_C-exten. DR InterPro; IPR002987; NaCa_exhngr1. 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:SF6; SODIUM_CALCIUM EXCHANGER 1; 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 PRINTS; PR01260; NACAEXCHNGR1. DR SMART; SM00237; Calx_beta; 2. DR SUPFAM; SSF141072; CalX-like; 2. DR Genevisible; P32418; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Antiport; Calcium; Calcium transport; KW Calmodulin-binding; Cell membrane; Glycoprotein; Ion transport; Membrane; KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Signal; Sodium; KW Sodium transport; Transmembrane; Transmembrane helix; Transport. FT SIGNAL 1..35 FT /evidence="ECO:0000255" FT CHAIN 36..973 FT /note="Sodium/calcium exchanger 1" FT /id="PRO_0000019379" FT TOPO_DOM 36..74 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 75..95 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 96..136 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 137..157 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 158..170 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 171..191 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 192..204 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 205..225 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 226..231 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 232..252 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 253..800 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 801..821 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 822..824 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 825..845 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 846..874 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 875..895 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 896..906 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 907..927 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 928..944 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 945..965 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 966..973 FT /note="Extracellular" FT /evidence="ECO:0000255" FT REPEAT 141..181 FT /note="Alpha-1" FT DOMAIN 396..496 FT /note="Calx-beta 1" FT DOMAIN 527..627 FT /note="Calx-beta 2" FT REPEAT 842..878 FT /note="Alpha-2" FT REGION 254..273 FT /note="Putative calmodulin-binding region" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 420 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 420 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 420 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 456 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 456 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 481 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 482 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 482 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 482 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 482 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 484 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 486 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 486 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 486 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 489 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 533 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 534 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 535 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 535 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 551 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 587 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 613 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 613 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 614 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 615 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 615 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250|UniProtKB:P23685" FT BINDING 718 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:P23685" FT MOD_RES 285 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70414" FT MOD_RES 392 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70414, ECO:0000255" FT CARBOHYD 44 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 605..613 FT /note="TISVKVIDD -> IITIRIFDR (in isoform 3, isoform 7 and FT isoform 10)" FT /evidence="ECO:0000303|PubMed:10908415, FT ECO:0000303|PubMed:11241183, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:8048567, ECO:0000303|Ref.3" FT /id="VSP_003397" FT VAR_SEQ 619..645 FT /note="NKTFFLEIGEPRLVEMSEKKALLLNEL -> ECSFSLVLEEPKWIRRGMK FT (in isoform 3, isoform 7 and isoform 10)" FT /evidence="ECO:0000303|PubMed:10908415, FT ECO:0000303|PubMed:11241183, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:8048567, ECO:0000303|Ref.3" FT /id="VSP_003398" FT VAR_SEQ 652..679 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11241183, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:8048567" FT /id="VSP_003400" FT VAR_SEQ 652..656 FT /note="Missing (in isoform 7 and isoform 5)" FT /evidence="ECO:0000303|PubMed:11241183, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3, FT ECO:0000303|Ref.8" FT /id="VSP_003399" FT VARIANT 692 FT /note="E -> V (in dbSNP:rs5557)" FT /id="VAR_014847" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 65..68 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 72..106 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 108..114 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 118..120 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 124..131 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 134..144 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 146..158 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 166..189 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 201..223 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 232..254 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 259..261 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 262..268 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 270..280 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 407..419 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 420..422 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 423..434 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 436..438 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 440..447 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 449..451 FT /evidence="ECO:0007829|PDB:8SGJ" FT TURN 453..455 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 461..466 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 472..479 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 489..500 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 519..521 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 526..532 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 539..543 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 545..550 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 555..564 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 568..577 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 579..581 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 584..588 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 592..597 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 603..610 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 619..626 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 630..634 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 636..641 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 648..655 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 658..663 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 672..676 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 692..700 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 711..717 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 720..731 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 743..751 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 773..789 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 797..800 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 801..829 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 833..839 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 841..845 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 847..859 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 860..863 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 864..879 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 881..895 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 904..927 FT /evidence="ECO:0007829|PDB:8SGJ" FT TURN 931..933 FT /evidence="ECO:0007829|PDB:8SGJ" FT STRAND 935..938 FT /evidence="ECO:0007829|PDB:8SGJ" FT HELIX 941..966 FT /evidence="ECO:0007829|PDB:8SGJ" SQ SEQUENCE 973 AA; 108547 MW; 17DFC1B1F15921D8 CRC64; MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMFL GVSIIADRFM SSIEVITSQE KEITIKKPNG ETTKTTVRIW NETVSNLTLM ALGSSAPEIL LSVIEVCGHN FTAGDLGPST IVGSAAFNMF IIIALCVYVV PDGETRKIKH LRVFFVTAAW SIFAYTWLYI ILSVISPGVV EVWEGLLTFF FFPICVVFAW VADRRLLFYK YVYKRYRAGK QRGMIIEHEG DRPSSKTEIE MDGKVVNSHV ENFLDGALVL EVDERDQDDE EARREMARIL KELKQKHPDK EIEQLIELAN YQVLSQQQKS RAFYRIQATR LMTGAGNILK RHAADQARKA VSMHEVNTEV TENDPVSKIF FEQGTYQCLE NCGTVALTII RRGGDLTNTV FVDFRTEDGT ANAGSDYEFT EGTVVFKPGD TQKEIRVGII DDDIFEEDEN FLVHLSNVKV SSEASEDGIL EANHVSTLAC LGSPSTATVT IFDDDHAGIF TFEEPVTHVS ESIGIMEVKV LRTSGARGNV IVPYKTIEGT ARGGGEDFED TCGELEFQND EIVKTISVKV IDDEEYEKNK TFFLEIGEPR LVEMSEKKAL LLNELGGFTI TGKYLFGQPV FRKVHAREHP ILSTVITIAD EYDDKQPLTS KEEEERRIAE MGRPILGEHT KLEVIIEESY EFKSTVDKLI KKTNLALVVG TNSWREQFIE AITVSAGEDD DDDECGEEKL PSCFDYVMHF LTVFWKVLFA FVPPTEYWNG WACFIVSILM IGLLTAFIGD LASHFGCTIG LKDSVTAVVF VALGTSVPDT FASKVAATQD QYADASIGNV TGSNAVNVFL GIGVAWSIAA IYHAANGEQF KVSPGTLAFS VTLFTIFAFI NVGVLLYRRR PEIGGELGGP RTAKLLTSCL FVLLWLLYIF FSSLEAYCHI KGF //