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Protein

Sodium/calcium exchanger 1

Gene

Slc8a1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates the exchange of one Ca2+ ion against three to four Na+ ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca2+ levels and Ca2+-dependent cellular processes (PubMed:8659820). Contributes to Ca2+ transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca2+ levels due to release of Ca2+ stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca2+ from the cell during the next phase, so that cytoplasmic Ca2+ levels rapidly return to baseline (PubMed:10967099). Required for normal embryonic heart development and the onset of heart contractions (PubMed:10967099).Curated2 Publications

Enzyme regulationi

Activated by micromolar levels of Ca2+.Curated

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi417 – 4171Calcium 1By similarity
Metal bindingi417 – 4171Calcium 2By similarity
Metal bindingi417 – 4171Calcium 3By similarity
Metal bindingi453 – 4531Calcium 1By similarity
Metal bindingi453 – 4531Calcium 4By similarity
Metal bindingi478 – 4781Calcium 2By similarity
Metal bindingi479 – 4791Calcium 1By similarity
Metal bindingi479 – 4791Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi479 – 4791Calcium 3By similarity
Metal bindingi479 – 4791Calcium 4By similarity
Metal bindingi481 – 4811Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi483 – 4831Calcium 1By similarity
Metal bindingi483 – 4831Calcium 3By similarity
Metal bindingi483 – 4831Calcium 4By similarity
Metal bindingi486 – 4861Calcium 4By similarity
Metal bindingi530 – 5301Calcium 3By similarity
Metal bindingi531 – 5311Calcium 2By similarity
Metal bindingi532 – 5321Calcium 2By similarity
Metal bindingi532 – 5321Calcium 3By similarity
Metal bindingi548 – 5481Calcium 5By similarity
Metal bindingi584 – 5841Calcium 6By similarity
Metal bindingi610 – 6101Calcium 5By similarity
Metal bindingi610 – 6101Calcium 6By similarity
Metal bindingi611 – 6111Calcium 6By similarity
Metal bindingi612 – 6121Calcium 5; via carbonyl oxygenBy similarity
Metal bindingi612 – 6121Calcium 6By similarity
Metal bindingi715 – 7151Calcium 5By similarity

GO - Molecular functioni

  • ankyrin binding Source: BHF-UCL
  • calcium:sodium antiporter activity Source: BHF-UCL
  • calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  • calcium ion binding Source: UniProtKB
  • cytoskeletal protein binding Source: MGI
  • ion channel binding Source: BHF-UCL

GO - Biological processi

  • calcium ion export Source: BHF-UCL
  • calcium ion homeostasis Source: BHF-UCL
  • calcium ion import Source: BHF-UCL
  • calcium ion transmembrane transport Source: UniProtKB
  • calcium ion transport Source: MGI
  • calcium ion transport into cytosol Source: BHF-UCL
  • cardiac muscle cell development Source: BHF-UCL
  • cardiac muscle contraction Source: MGI
  • cell communication Source: InterPro
  • cellular response to caffeine Source: BHF-UCL
  • cellular response to reactive oxygen species Source: MGI
  • cellular sodium ion homeostasis Source: MGI
  • embryonic heart tube development Source: MGI
  • embryonic placenta development Source: MGI
  • heart morphogenesis Source: MGI
  • muscle fiber development Source: MGI
  • negative regulation of cytosolic calcium ion concentration Source: BHF-UCL
  • positive regulation of bone mineralization Source: MGI
  • positive regulation of the force of heart contraction Source: MGI
  • post-embryonic development Source: MGI
  • regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  • regulation of heart rate Source: BHF-UCL
  • regulation of the force of heart contraction Source: MGI
  • relaxation of smooth muscle Source: BHF-UCL
  • response to muscle stretch Source: MGI
  • sodium ion export Source: BHF-UCL
  • sodium ion import Source: BHF-UCL
  • sodium ion transmembrane transport Source: MGI
  • sodium ion transport Source: MGI
  • vascular smooth muscle contraction Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Antiport, Calcium transport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calcium, Calmodulin-binding, Metal-binding, Sodium

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/calcium exchanger 1
Alternative name(s):
Na(+)/Ca(2+)-exchange protein 1
Solute carrier family 8 member 1
Gene namesi
Name:Slc8a1
Synonyms:Ncx
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:107956. Slc8a1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 7139ExtracellularSequence analysisAdd
BLAST
Transmembranei72 – 9221HelicalSequence analysisAdd
BLAST
Topological domaini93 – 13341CytoplasmicSequence analysisAdd
BLAST
Transmembranei134 – 15421HelicalSequence analysisAdd
BLAST
Topological domaini155 – 16713ExtracellularSequence analysisAdd
BLAST
Transmembranei168 – 18821HelicalSequence analysisAdd
BLAST
Topological domaini189 – 20113CytoplasmicSequence analysisAdd
BLAST
Transmembranei202 – 22221HelicalSequence analysisAdd
BLAST
Topological domaini223 – 2286ExtracellularSequence analysis
Transmembranei229 – 24921HelicalSequence analysisAdd
BLAST
Topological domaini250 – 797548CytoplasmicSequence analysisAdd
BLAST
Transmembranei798 – 81821HelicalSequence analysisAdd
BLAST
Topological domaini819 – 8213ExtracellularSequence analysis
Transmembranei822 – 84221HelicalSequence analysisAdd
BLAST
Topological domaini843 – 87129CytoplasmicSequence analysisAdd
BLAST
Transmembranei872 – 89221HelicalSequence analysisAdd
BLAST
Topological domaini893 – 90311ExtracellularSequence analysisAdd
BLAST
Transmembranei904 – 92421HelicalSequence analysisAdd
BLAST
Topological domaini925 – 94117CytoplasmicSequence analysisAdd
BLAST
Transmembranei942 – 96221HelicalSequence analysisAdd
BLAST
Topological domaini963 – 9708ExtracellularSequence analysis

GO - Cellular componenti

  • basolateral plasma membrane Source: MGI
  • integral component of membrane Source: MGI
  • integral component of plasma membrane Source: MGI
  • intracellular Source: GOC
  • intrinsic component of plasma membrane Source: UniProtKB
  • membrane Source: MGI
  • plasma membrane Source: MGI
  • sarcolemma Source: BHF-UCL
  • T-tubule Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Complete embryonic lethality at about 9.5 dpc. At 9.5 dpc, mutant embryos display strongly decreased body size, an absence of blood vessels in the vitelline sac, and defective heart beat. Contrary to wild type hearts that show regular contractions, about 70% of the mutants have no spontaneous contractions of the heart, and the remainder show only very slow and arrhythmic heart contractions. Mutant hearts have thinner ventricles, contain fewer cardiac myocytes, and display an increased number of apoptotic cells. Mutant hearts do not show fast Ca2+ transients and display lack of sodium/calcium exchange activity. In mutant hearts, caffeine stimulates normal release of intracellular Ca2+ stores from the endoplasmic reticulum into the cytoplasm, but the subsequent decrease of the high cytoplasmic Ca2+ levels is impaired (PubMed:10967099). At 9.5 dpc, embryonic cardiomyocytes show severe disorganization of the myofibrils and swollen mitochondria (PubMed:12781968).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence analysisAdd
BLAST
Chaini33 – 970938Sodium/calcium exchanger 1PRO_0000019380Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi41 – 411N-linked (GlcNAc...)Sequence analysis
Glycosylationi157 – 1571N-linked (GlcNAc...)Sequence analysis
Modified residuei282 – 2821PhosphoserineCombined sources
Modified residuei389 – 3891PhosphoserineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP70414.
PaxDbiP70414.
PRIDEiP70414.

PTM databases

iPTMnetiP70414.
PhosphoSiteiP70414.
SwissPalmiP70414.

Expressioni

Tissue specificityi

Detected in heart, kidney and brain (at protein level).1 Publication

Developmental stagei

At 9.5 dpc, expression is restricted to the embryonic heart, and is not detectable in any other part of the body.1 Publication

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
NanogQ80Z649EBI-2312694,EBI-2312517
Nr0b1Q610662EBI-2312694,EBI-2312665

GO - Molecular functioni

  • ankyrin binding Source: BHF-UCL
  • cytoskeletal protein binding Source: MGI
  • ion channel binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi203320. 2 interactions.
IntActiP70414. 6 interactions.
STRINGi10090.ENSMUSP00000083725.

Structurei

3D structure databases

ProteinModelPortaliP70414.
SMRiP70414. Positions 403-724.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati138 – 17841Alpha-1Add
BLAST
Domaini393 – 493101Calx-beta 1Add
BLAST
Domaini524 – 624101Calx-beta 2Add
BLAST
Repeati839 – 87537Alpha-2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni251 – 27020Putative calmodulin-binding regionBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi236 – 2394Poly-Phe
Compositional biasi689 – 6924Poly-Glu
Compositional biasi756 – 7605Poly-Asp

Domaini

The cytoplasmic Calx-beta domains bind the regulatory Ca2+. The first Calx-beta domain can bind up to four Ca2+ ions. The second domain can bind another two Ca2+ ions that are essential for calcium-regulated ion exchange.By similarity

Sequence similaritiesi

Contains 2 Calx-beta domains.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiP70414.
KOiK05849.
PhylomeDBiP70414.

Family and domain databases

InterProiIPR003644. Calx_beta.
IPR001623. DnaJ_domain.
IPR004836. Na_Ca_Ex.
IPR032452. Na_Ca_Ex_C-exten.
IPR002987. NaCa_exhngr1.
IPR004837. NaCa_Exmemb.
[Graphical view]
PfamiPF03160. Calx-beta. 2 hits.
PF01699. Na_Ca_ex. 2 hits.
PF16494. Na_Ca_ex_C. 1 hit.
[Graphical view]
PRINTSiPR01259. NACAEXCHNGR.
PR01260. NACAEXCHNGR1.
SMARTiSM00237. Calx_beta. 2 hits.
[Graphical view]
TIGRFAMsiTIGR00845. caca. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P70414-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRLSLPPNV SMGFRLVALV ALLFSHVDHI TADTEAETGG NETTECTGSY
60 70 80 90 100
YCKKGVILPI WEPQDPSFGD KIARATVYFV AMVYMFLGVS IIADRFMSSI
110 120 130 140 150
EVITSQEKEI TIKKPNGETT KTTVRIWNET VSNLTLMALG SSAPEILLSV
160 170 180 190 200
IEVCGHNFTA GDLGPSTIVG SAAFNMFIII ALCVYVVPDG ETRKIKHLRV
210 220 230 240 250
FFVTAAWSIF AYTWLYIILS VSSPGVVEVW EGLLTFFFFP ICVVFAWVAD
260 270 280 290 300
RRLLFYKYVY KRYRAGKQRG MIIEHEGDRP ASKTEIEMDG KVVNSHVDNF
310 320 330 340 350
LDGALVLEVD ERDQDDEEAR REMARILKEL KQKHPEKEIE QLIELANYQV
360 370 380 390 400
LSQQQKSRAF YRIQATRLMT GAGNILKRHA ADQARKAVSM HEVNMEMAEN
410 420 430 440 450
DPVSKIFFEQ GTYQCLENCG TVALTIMRRG GDLSTTVFVD FRTEDGTANA
460 470 480 490 500
ASDYEFTEGT VIFKPGETQK EIRVGIIDDD IFEEDENFLV HLSNVRVSSD
510 520 530 540 550
VSEDGILESN HASSIACLGS PSTATITIFD DDHAGIFTFE EPVTHVSESI
560 570 580 590 600
GIMEVKVLRT SGARGNVIIP YKTIEGTARG GGEDFEDTCG EPEFQNDEIV
610 620 630 640 650
KTISVKVIDD EEYEKNKTFF IEIGEPRLVE MSEKKALLLN ELGGFTLTGK
660 670 680 690 700
EMYGQPIFRK VHARDHPIPS TVITISEEYD DKQPLTSKEE EERRIAEMGR
710 720 730 740 750
PILGEHTKLE VIIQESYEFK STVDKLIKKT NLALVVGTNS WREQFIEAIT
760 770 780 790 800
VSAGEDDDDD ECGEEKLPSC FDYVMHFLTV FWKVLFAFVP PTEYWNGWAC
810 820 830 840 850
FIVSILMIGL LTAFIGDLAS HFGCTIGLKD SVTAVVFVAL GTSVPDTFAS
860 870 880 890 900
KVAATQDQYA DASIGNVTGS NAVNVFLGIG VAWSIAAIYH AANGEQFKVS
910 920 930 940 950
PGTLAFSVTL FTIFAFINVG VLLYRRRPEI GGELGGPRTA KLLTSSLFVL
960 970
LWLLYIFFSS LEAYCHIKGF
Length:970
Mass (Da):108,035
Last modified:February 1, 1997 - v1
Checksum:iF5FC0BD07F2B6602
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70033 mRNA. Translation: AAB46708.1.
CCDSiCCDS37706.1.
RefSeqiNP_035536.2. NM_011406.3.
UniGeneiMm.265834.
Mm.489060.

Genome annotation databases

GeneIDi20541.
KEGGimmu:20541.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70033 mRNA. Translation: AAB46708.1.
CCDSiCCDS37706.1.
RefSeqiNP_035536.2. NM_011406.3.
UniGeneiMm.265834.
Mm.489060.

3D structure databases

ProteinModelPortaliP70414.
SMRiP70414. Positions 403-724.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203320. 2 interactions.
IntActiP70414. 6 interactions.
STRINGi10090.ENSMUSP00000083725.

PTM databases

iPTMnetiP70414.
PhosphoSiteiP70414.
SwissPalmiP70414.

Proteomic databases

MaxQBiP70414.
PaxDbiP70414.
PRIDEiP70414.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi20541.
KEGGimmu:20541.

Organism-specific databases

CTDi6546.
MGIiMGI:107956. Slc8a1.

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiP70414.
KOiK05849.
PhylomeDBiP70414.

Miscellaneous databases

ChiTaRSiSlc8a1. mouse.
PROiP70414.
SOURCEiSearch...

Family and domain databases

InterProiIPR003644. Calx_beta.
IPR001623. DnaJ_domain.
IPR004836. Na_Ca_Ex.
IPR032452. Na_Ca_Ex_C-exten.
IPR002987. NaCa_exhngr1.
IPR004837. NaCa_Exmemb.
[Graphical view]
PfamiPF03160. Calx-beta. 2 hits.
PF01699. Na_Ca_ex. 2 hits.
PF16494. Na_Ca_ex_C. 1 hit.
[Graphical view]
PRINTSiPR01259. NACAEXCHNGR.
PR01260. NACAEXCHNGR1.
SMARTiSM00237. Calx_beta. 2 hits.
[Graphical view]
TIGRFAMsiTIGR00845. caca. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of the mouse cardiac Na(+)-Ca2+ exchanger and functional expression in Xenopus oocytes."
    Kim I., Lee C.O.
    Ann. N. Y. Acad. Sci. 779:126-128(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
    Strain: C57BL/6J.
  2. Cited for: DISRUPTION PHENOTYPE, FUNCTION, DEVELOPMENTAL STAGE.
  3. "Na+/Ca2+ exchanger-deficient mice have disorganized myofibrils and swollen mitochondria in cardiomyocytes."
    Wakimoto K., Fujimura H., Iwamoto T., Oka T., Kobayashi K., Kita S., Kudoh S., Kuro-o M., Nabeshima Y., Shigekawa M., Imai Y., Komuro I.
    Comp. Biochem. Physiol. 135:9-15(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-282 AND SER-389, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Heart, Kidney, Lung and Spleen.
  5. "The SLC8 gene family of sodium-calcium exchangers (NCX) - structure, function, and regulation in health and disease."
    Khananshvili D.
    Mol. Aspects Med. 34:220-235(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiNAC1_MOUSE
AccessioniPrimary (citable) accession number: P70414
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: June 8, 2016
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.