NAC1_HUMAN
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 03-AUG-2022, entry version 204.
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};
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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 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. [P32418-1]
DR RefSeq; XP_006712146.1; XM_006712083.3. [P32418-1]
DR RefSeq; XP_006712147.1; XM_006712084.3. [P32418-1]
DR RefSeq; XP_006712148.1; XM_006712085.3. [P32418-1]
DR RefSeq; XP_011531356.1; XM_011533054.2. [P32418-1]
DR RefSeq; XP_011531357.1; XM_011533055.2. [P32418-1]
DR RefSeq; XP_011531358.1; XM_011533056.1. [P32418-1]
DR RefSeq; XP_016860235.1; XM_017004746.1. [P32418-1]
DR RefSeq; XP_016860237.1; XM_017004748.1.
DR RefSeq; XP_016860238.1; XM_017004749.1. [P32418-1]
DR RefSeq; XP_016860239.1; XM_017004750.1. [P32418-1]
DR RefSeq; XP_016860240.1; XM_017004751.1. [P32418-1]
DR RefSeq; XP_016860241.1; XM_017004752.1. [P32418-1]
DR RefSeq; XP_016860242.1; XM_017004753.1. [P32418-1]
DR RefSeq; XP_016860243.1; XM_017004754.1.
DR RefSeq; XP_016860247.1; XM_017004758.1.
DR AlphaFoldDB; P32418; -.
DR SMR; P32418; -.
DR BioGRID; 112436; 3.
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 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; P32418; -.
DR PeptideAtlas; P32418; -.
DR PRIDE; P32418; -.
DR ProteomicsDB; 54873; -. [P32418-1]
DR ProteomicsDB; 54874; -. [P32418-2]
DR ProteomicsDB; 54875; -. [P32418-3]
DR ProteomicsDB; 54876; -. [P32418-4]
DR Antibodypedia; 29673; 201 antibodies from 32 providers.
DR DNASU; 6546; -.
DR Ensembl; ENST00000332839.8; ENSP00000332931.4; ENSG00000183023.18. [P32418-1]
DR Ensembl; ENST00000402441.5; ENSP00000385188.1; ENSG00000183023.18. [P32418-2]
DR Ensembl; ENST00000403092.5; ENSP00000384763.1; ENSG00000183023.18. [P32418-1]
DR Ensembl; ENST00000405269.5; ENSP00000385535.1; ENSG00000183023.18. [P32418-2]
DR Ensembl; ENST00000405901.7; ENSP00000385678.3; ENSG00000183023.18. [P32418-5]
DR Ensembl; ENST00000406391.2; ENSP00000385811.2; ENSG00000183023.18. [P32418-2]
DR Ensembl; ENST00000406785.6; ENSP00000383886.1; ENSG00000183023.18. [P32418-2]
DR Ensembl; ENST00000408028.6; ENSP00000384908.2; ENSG00000183023.18. [P32418-4]
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 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; VSAETEM; -.
DR OrthoDB; 490546at2759; -.
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; 6 hits in 1074 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 178 other tissues.
DR ExpressionAtlas; P32418; baseline and differential.
DR Genevisible; P32418; HS.
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:0043198; C:dendritic shaft; IEA:Ensembl.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0014704; C:intercalated disc; ISS:BHF-UCL.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
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:ARUK-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:1905060; F:calcium:cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration; IEA:Ensembl.
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:0015491; F:cation:cation antiporter activity; IBA:GO_Central.
DR GO; GO:0008092; F:cytoskeletal protein binding; IDA:BHF-UCL.
DR GO; GO:0099580; F:ion antiporter activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
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:0006874; P:cellular calcium ion homeostasis; ISS:ARUK-UCL.
DR GO; GO:0071313; P:cellular response to caffeine; ISS:BHF-UCL.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:BHF-UCL.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IDA:BHF-UCL.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; TAS:BHF-UCL.
DR GO; GO:0030001; P:metal ion transport; IBA:GO_Central.
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:0010763; P:positive regulation of fibroblast migration; IEA:Ensembl.
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:0002028; P:regulation of sodium ion transport; IEA:Ensembl.
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:0033198; P:response to ATP; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:0035994; P:response to muscle stretch; IMP:BHF-UCL.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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:0021537; P:telencephalon development; IEA:Ensembl.
DR GO; GO:0014829; P:vascular associated smooth muscle contraction; ISS:BHF-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; 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 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; SSF141072; 2.
DR TIGRFAMs; TIGR00845; caca; 1.
PE 1: Evidence at protein level;
KW 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"
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
