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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)DescriptionActionsGraphical viewLength
Metal bindingi417Calcium 1By similarity1
Metal bindingi417Calcium 2By similarity1
Metal bindingi417Calcium 3By similarity1
Metal bindingi453Calcium 1By similarity1
Metal bindingi453Calcium 4By similarity1
Metal bindingi478Calcium 2By similarity1
Metal bindingi479Calcium 1By similarity1
Metal bindingi479Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi479Calcium 3By similarity1
Metal bindingi479Calcium 4By similarity1
Metal bindingi481Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi483Calcium 1By similarity1
Metal bindingi483Calcium 3By similarity1
Metal bindingi483Calcium 4By similarity1
Metal bindingi486Calcium 4By similarity1
Metal bindingi530Calcium 3By similarity1
Metal bindingi531Calcium 2By similarity1
Metal bindingi532Calcium 2By similarity1
Metal bindingi532Calcium 3By similarity1
Metal bindingi548Calcium 5By similarity1
Metal bindingi584Calcium 6By similarity1
Metal bindingi610Calcium 5By similarity1
Metal bindingi610Calcium 6By similarity1
Metal bindingi611Calcium 6By similarity1
Metal bindingi612Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi612Calcium 6By similarity1
Metal bindingi715Calcium 5By similarity1

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 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)DescriptionActionsGraphical viewLength
Topological domaini33 – 71ExtracellularSequence analysisAdd BLAST39
Transmembranei72 – 92HelicalSequence analysisAdd BLAST21
Topological domaini93 – 133CytoplasmicSequence analysisAdd BLAST41
Transmembranei134 – 154HelicalSequence analysisAdd BLAST21
Topological domaini155 – 167ExtracellularSequence analysisAdd BLAST13
Transmembranei168 – 188HelicalSequence analysisAdd BLAST21
Topological domaini189 – 201CytoplasmicSequence analysisAdd BLAST13
Transmembranei202 – 222HelicalSequence analysisAdd BLAST21
Topological domaini223 – 228ExtracellularSequence analysis6
Transmembranei229 – 249HelicalSequence analysisAdd BLAST21
Topological domaini250 – 797CytoplasmicSequence analysisAdd BLAST548
Transmembranei798 – 818HelicalSequence analysisAdd BLAST21
Topological domaini819 – 821ExtracellularSequence analysis3
Transmembranei822 – 842HelicalSequence analysisAdd BLAST21
Topological domaini843 – 871CytoplasmicSequence analysisAdd BLAST29
Transmembranei872 – 892HelicalSequence analysisAdd BLAST21
Topological domaini893 – 903ExtracellularSequence analysisAdd BLAST11
Transmembranei904 – 924HelicalSequence analysisAdd BLAST21
Topological domaini925 – 941CytoplasmicSequence analysisAdd BLAST17
Transmembranei942 – 962HelicalSequence analysisAdd BLAST21
Topological domaini963 – 970ExtracellularSequence analysis8

GO - Cellular componenti

  • basolateral plasma membrane Source: MGI
  • integral component of membrane Source: MGI
  • integral component of plasma membrane Source: MGI
  • 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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000001938033 – 970Sodium/calcium exchanger 1Add BLAST938

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi41N-linked (GlcNAc...)Sequence analysis1
Glycosylationi157N-linked (GlcNAc...)Sequence analysis1
Modified residuei282PhosphoserineCombined sources1
Modified residuei389PhosphoserineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP70414.
PaxDbiP70414.
PeptideAtlasiP70414.
PRIDEiP70414.

PTM databases

iPTMnetiP70414.
PhosphoSitePlusiP70414.
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 interactors.
IntActiP70414. 6 interactors.
STRINGi10090.ENSMUSP00000083725.

Structurei

3D structure databases

ProteinModelPortaliP70414.
SMRiP70414.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati138 – 178Alpha-1Add BLAST41
Domaini393 – 493Calx-beta 1Add BLAST101
Domaini524 – 624Calx-beta 2Add BLAST101
Repeati839 – 875Alpha-2Add BLAST37

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni251 – 270Putative calmodulin-binding regionBy similarityAdd BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi236 – 239Poly-Phe4
Compositional biasi689 – 692Poly-Glu4
Compositional biasi756 – 760Poly-Asp5

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203320. 2 interactors.
IntActiP70414. 6 interactors.
STRINGi10090.ENSMUSP00000083725.

PTM databases

iPTMnetiP70414.
PhosphoSitePlusiP70414.
SwissPalmiP70414.

Proteomic databases

MaxQBiP70414.
PaxDbiP70414.
PeptideAtlasiP70414.
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...

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: November 2, 2016
This is version 146 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.