Sodium/calcium exchanger 1

NameSodium/calcium exchanger 1
Synonyms
  • CNC
  • Na(+)/Ca(2+)-exchange protein 1
  • NCX1
  • Solute carrier family 8 member 1
Gene NameSLC8A1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001963|Sodium/calcium exchanger 1
MYNMRRLSLSPTFSMGFHLLVTVSLLFSHVDHVIAETEMEGEGNETGECTGSYYCKKGVI
LPIWEPQDPSFGDKIARATVYFVAMVYMFLGVSIIADRFMSSIEVITSQEKEITIKKPNG
ETTKTTVRIWNETVSNLTLMALGSSAPEILLSVIEVCGHNFTAGDLGPSTIVGSAAFNMF
IIIALCVYVVPDGETRKIKHLRVFFVTAAWSIFAYTWLYIILSVISPGVVEVWEGLLTFF
FFPICVVFAWVADRRLLFYKYVYKRYRAGKQRGMIIEHEGDRPSSKTEIEMDGKVVNSHV
ENFLDGALVLEVDERDQDDEEARREMARILKELKQKHPDKEIEQLIELANYQVLSQQQKS
RAFYRIQATRLMTGAGNILKRHAADQARKAVSMHEVNTEVTENDPVSKIFFEQGTYQCLE
NCGTVALTIIRRGGDLTNTVFVDFRTEDGTANAGSDYEFTEGTVVFKPGDTQKEIRVGII
DDDIFEEDENFLVHLSNVKVSSEASEDGILEANHVSTLACLGSPSTATVTIFDDDHAGIF
TFEEPVTHVSESIGIMEVKVLRTSGARGNVIVPYKTIEGTARGGGEDFEDTCGELEFQND
EIVKTISVKVIDDEEYEKNKTFFLEIGEPRLVEMSEKKALLLNELGGFTITGKYLFGQPV
FRKVHAREHPILSTVITIADEYDDKQPLTSKEEEERRIAEMGRPILGEHTKLEVIIEESY
EFKSTVDKLIKKTNLALVVGTNSWREQFIEAITVSAGEDDDDDECGEEKLPSCFDYVMHF
LTVFWKVLFAFVPPTEYWNGWACFIVSILMIGLLTAFIGDLASHFGCTIGLKDSVTAVVF
VALGTSVPDTFASKVAATQDQYADASIGNVTGSNAVNVFLGIGVAWSIAAIYHAANGEQF
KVSPGTLAFSVTLFTIFAFINVGVLLYRRRPEIGGELGGPRTAKLLTSCLFVLLWLLYIF
FSSLEAYCHIKGF
Number of residues973
Molecular Weight108546.06
Theoretical pI4.64
GO Classification
Functions
  • ankyrin binding
  • ion channel binding
  • calcium ion binding
  • calcium
  • cytoskeletal protein binding
Processes
  • regulation of cell communication by electrical coupling
  • calcium ion import
  • sodium ion transmembrane transport
  • relaxation of smooth muscle
  • calcium ion transport into cytosol
  • cardiac muscle contraction
  • transmembrane transport
  • sodium ion import
  • embryonic placenta development
  • membrane depolarization during cardiac muscle cell action potential
  • response to hydrogen peroxide
  • vascular smooth muscle contraction
  • heart morphogenesis
  • regulation of heart rate
  • post-embryonic development
  • regulation of the force of heart contraction
  • cellular response to hypoxia
  • response to muscle stretch
  • embryonic heart tube development
  • cell communication by electrical coupling involved in cardiac conduction
  • response to nutrient
  • ion transport
  • positive regulation of bone mineralization
  • calcium ion transmembrane transport
  • cardiac muscle cell development
  • muscle contraction
  • response to immobilization stress
  • positive regulation of fibroblast migration
  • blood coagulation
  • muscle fiber development
  • telencephalon development
  • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
  • regulation of cardiac muscle contraction by calcium ion signaling
  • regulation of sodium ion transport
  • relaxation of cardiac muscle
  • cellular response to caffeine
  • response to drug
  • response to ATP
  • positive regulation of the force of heart contraction
  • sodium ion export
  • response to glucose
  • calcium ion homeostasis
  • cellular response to reactive oxygen species
  • cellular response to cAMP
  • calcium ion export
  • negative regulation of cytosolic calcium ion concentration
  • cytosolic calcium ion transport
  • cellular sodium ion homeostasis
Components
  • integral component of plasma membrane
  • mitochondrion
  • basolateral plasma membrane
  • dendritic shaft
  • microtubule
  • dendritic spine
  • intercalated disc
  • plasma membrane
  • sarcolemma
  • T-tubule
  • Z disc
  • cytosol
General FunctionIon channel binding
Specific FunctionMediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:1374913, PubMed:11241183, PubMed:1476165). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions.
Pfam Domain Function
Transmembrane Regions75-95 137-157 171-191 205-225 232-252 801-821 825-845 875-895 907-927 945-965
GenBank Protein ID180673
UniProtKB IDP32418
UniProtKB Entry NameNAC1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0016275|Sodium/calcium exchanger 1 (SLC8A1)
ATGTACAACATGCGGCGATTAAGTCTTTCACCCACCTTTTCAATGGGATTTCATCTGTTA
GTTACTGTGAGTCTCTTATTTTCCCATGTGGACCATGTAATTGCTGAGACAGAAATGGAA
GGAGAAGGAAATGAAACTGGTGAATGTACTGGATCATATTACTGTAAGAAAGGGGTGATT
TTGCCCATTTGGGAACCCCAAGACCCTTCTTTTGGGGACAAAATTGCTAGAGCTACTGTG
TATTTTGTGGCCATGGTCTACATGTTTCTTGGAGTCTCTATCATAGCTGATCGGTTCATG
TCCTCTATAGAAGTCATCACATCTCAAGAAAAAGAAATAACCATAAAGAAACCCAATGGA
GAGACCACCAAGACAACTGTGAGGATCTGGAATGAAACAGTTTCTAACCTGACCTTGATG
GCCCTGGGATCTTCTGCTCCTGAGATTCTCCTTTCAGTAATTGAAGTGTGTGGCCATAAC
TTCACTGCAGGAGACCTCGGTCCTAGCACCATCGTGGGAAGTGCTGCATTCAATATGTTC
ATCATTATTGCACTCTGTGTTTATGTGGTGCCTGACGGAGAGACAAGGAAGATTAAGCAT
TTGCGTGTCTTCTTTGTGACAGCAGCCTGGAGCATCTTTGCCTACACCTGGCTTTACATT
ATTTTGTCTGTCATATCTCCTGGTGTTGTGGAGGTCTGGGAAGGTTTGCTTACTTTCTTC
TTCTTTCCCATCTGTGTTGTGTTCGCTTGGGTAGCGGATAGGAGACTTCTGTTTTACAAG
TATGTCTACAAGAGGTATCGAGCTGGCAAGCAGAGGGGGATGATTATTGAACATGAAGGA
GACAGGCCATCTTCTAAGACTGAAATTGAAATGGACGGGAAAGTGGTCAATTCTCATGTT
GAAAATTTCTTAGATGGTGCTCTGGTTCTGGAGGTGGATGAGAGGGACCAAGATGATGAA
GAAGCTAGGCGAGAAATGGCTAGGATTCTGAAGGAACTTAAGCAGAAGCATCCAGATAAA
GAAATAGAGCAATTAATAGAATTAGCTAACTACCAAGTCCTAAGTCAGCAGCAAAAAAGT
AGAGCATTTTATCGCATTCAAGCTACTCGCCTCATGACTGGAGCTGGCAACATTTTAAAG
AGGCATGCAGCTGACCAAGCAAGGAAGGCTGTCAGCATGCACGAGGTCAACACTGAAGTG
ACTGAAAATGACCCTGTTAGTAAGATCTTCTTTGAACAAGGGACATATCAGTGTCTGGAG
AACTGTGGTACTGTGGCCCTTACCATTATCCGCAGAGGTGGTGATTTGACTAACACTGTG
TTTGTTGACTTCAGAACAGAGGATGGCACAGCAAATGCTGGGTCTGATTATGAATTTACT
GAAGGAACTGTGGTGTTTAAGCCTGGTGATACCCAGAAGGAAATCAGAGTGGGTATCATA
GATGATGATATCTTTGAGGAGGATGAAAATTTCCTTGTGCATCTCAGCAATGTCAAAGTA
TCTTCTGAAGCTTCAGAAGATGGCATACTGGAAGCCAATCATGTTTCTACACTTGCTTGC
CTCGGATCTCCCTCCACTGCCACTGTAACTATTTTTGATGATGACCACGCAGGCATTTTT
ACTTTTGAGGAACCTGTGACTCATGTGAGTGAGAGCATTGGCATCATGGAGGTGAAAGTA
TTGAGAACATCTGGAGCTCGAGGAAATGTTATCGTTCCATATAAAACCATCGAAGGGACT
GCCAGAGGTGGAGGGGAGGATTTTGAGGACACTTGTGGAGAGCTCGAATTCCAGAATGAT
GAAATTGTCAAAACAATATCAGTCAAGGTAATTGATGATGAGGAGTATGAGAAAAACAAG
ACCTTCTTCCTTGAGATTGGAGAGCCCCGCCTGGTGGAGATGAGTGAGAAGAAAGCCCTG
TTATTGAATGAGCTTGGTGGCTTCACAATAACAGGCCAACCTGTCTTCAGGAAGGTTCAT
GCTAGAGAACATCCGATTCTCTCTACTGTAATCACCATTGCAGACGAATATGATGACAAG
CAGCCACTGACCAGCAAAGAGGAAGAGGAGAGGCGCATTGCAGAAATGGGGCGCCCCATC
CTGGGAGAGCACACCAAGTTGGAAGTGATCATTGAAGAATCCTATGAATTCAAGAGTACT
GTGGACAAACTCATTAAGAAGACAAACCTGGCCCTTGTGGTTGGGACTAACAGCTGGAGA
GAACAGTTCATTGAAGCTATCACTGTCAGTGCTGGGGAAGATGATGACGACGATGAATGT
GGGGAAGAGAAGCTGCCCTCCTGTTTCGATTACGTGATGCACTTTCTGACTGTGTTCTGG
AAGGTCCTGTTTGCCTTCGTCCCCCCTACTGAATACTGGAATGGCTGGGCGTGTTTCATT
GTCTCCATCCTCATGATTGGCCTACTGACAGCTTTCATTGGAGACCTGGCTTCCCACTTT
GGCTGCACCATTGGCCTGAAAGATTCTGTGACTGCAGTCGTGTTCGTCGCACTTGGAACA
TCAGTGCCAGACACATTTGCCAGCAAAGTGGCAGCCACCCAGGACCAGTATGCAGACGCC
TCCATAGGTAACGTCACGGGCAGCAACGCGGTGAATGTCTTCCTGGGAATCGGTGTGGCC
TGGTCCATCGCTGCCATCTACCACGCAGCCAATGGGGAACAGTTCAAAGTGTCCCCTGGC
ACACTAGCTTTCTCTGTCACTCTCTTCACCATTTTTGCTTTCATCAATGTGGGGGTGCTG
CTGTATCGGCGGAGGCCAGAAATCGGAGGTGAGCTGGGTGGGCCCCGGACTGCCAAGCTC
CTCACATCCTGCCTCTTTGTGCTCCTATGGCTCTTGTACATTTTCTTCTCCTCCCTGGAG
GCCTACTGCCACATAAAAGGCTTCTAA
GenBank Gene IDM91368
GeneCard IDNot Available
GenAtlas IDSLC8A1
HGNC IDHGNC:11068
Chromosome Location2
Locus2p23-p22
References
  1. Komuro I, Wenninger KE, Philipson KD, Izumo S: Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger cDNA. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4769-73. 1374913
  2. Van Eylen F, Bollen A, Herchuelz A: NCX1 Na/Ca exchanger splice variants in pancreatic islet cells. J Endocrinol. 2001 Mar;168(3):517-26. 11241183
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  5. Lundquist P, Lundgren T, Gritli-Linde A, Linde A: Na+/Ca2+ exchanger isoforms of rat odontoblasts and osteoblasts. Calcif Tissue Int. 2000 Jul;67(1):60-7. 10908415
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Loo TW, Clarke DM: Functional expression of human renal Na+/Ca2+ exchanger in insect cells. Am J Physiol. 1994 Jul;267(1 Pt 2):F70-4. 8048567
  8. Kofuji P, Hadley RW, Kieval RS, Lederer WJ, Schulze DH: Expression of the Na-Ca exchanger in diverse tissues: a study using the cloned human cardiac Na-Ca exchanger. Am J Physiol. 1992 Dec;263(6 Pt 1):C1241-9. 1476165
  9. Ren X, Philipson KD: The topology of the cardiac Na(+)/Ca(2)(+) exchanger, NCX1. J Mol Cell Cardiol. 2013 Apr;57:68-71. doi: 10.1016/j.yjmcc.2013.01.010. Epub 2013 Jan 31. 23376057
  10. Khananshvili D: The SLC8 gene family of sodium-calcium exchangers (NCX) - structure, function, and regulation in health and disease. Mol Aspects Med. 2013 Apr-Jun;34(2-3):220-35. doi: 10.1016/j.mam.2012.07.003. 23506867