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Protein

Sodium/calcium exchanger 1

Gene

SLC8A1

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: -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:1700476, PubMed:1785844, PubMed:9486131, PubMed:17962412). 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. Required for normal embryonic heart development and the onset of heart contractions (By similarity).By similarity5 Publications

Activity regulationi

Activated by micromolar levels of Ca2+. In the absence of regulatory Ca2+, channels open rapidly, and then inactivate rapidly. Inactivation is enhanced by Na+ and is inhibited by micromolar levels of Ca2+.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi417Calcium 1Combined sources1
Metal bindingi417Calcium 2Combined sources1
Metal bindingi417Calcium 3Combined sources1
Metal bindingi453Calcium 1Combined sources1
Metal bindingi453Calcium 4Combined sources1
Metal bindingi478Calcium 2Combined sources1
Metal bindingi479Calcium 1Combined sources1
Metal bindingi479Calcium 2; via carbonyl oxygenCombined sources1
Metal bindingi479Calcium 3Combined sources1
Metal bindingi479Calcium 4Combined sources1
Metal bindingi481Calcium 3; via carbonyl oxygenCombined sources1
Metal bindingi483Calcium 1Combined sources1
Metal bindingi483Calcium 3Combined sources1
Metal bindingi483Calcium 4Combined sources1
Metal bindingi486Calcium 4Combined sources1
Metal bindingi530Calcium 3Combined sources1
Metal bindingi531Calcium 2Combined sources1
Metal bindingi532Calcium 2Combined sources1
Metal bindingi532Calcium 3Combined sources1
Metal bindingi548Calcium 5Combined sources1
Metal bindingi584Calcium 6Combined sources1
Metal bindingi610Calcium 5Combined sources1
Metal bindingi610Calcium 6Combined sources1
Metal bindingi611Calcium 6Combined sources1
Metal bindingi612Calcium 5; via carbonyl oxygenCombined sources1
Metal bindingi612Calcium 6Combined sources1
Metal bindingi715Calcium 5Combined sources1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding
Biological processAntiport, Calcium transport, Ion transport, Sodium transport, Transport
LigandCalcium, Metal-binding, Sodium

Enzyme and pathway databases

ReactomeiR-CFA-418359 Reduction of cytosolic Ca++ levels
R-CFA-425561 Sodium/Calcium exchangers
R-CFA-5578775 Ion homeostasis

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:NCX11 Publication
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Chromosome 17

Organism-specific databases

VGNCiVGNC:46480 SLC8A1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 797CytoplasmicCuratedAdd 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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi548E → L: Abolishes regulation by micromolar Ca(2+). 1 Publication1
Mutagenesisi584D → V: No effect on regulation by micromolar Ca(2+). 1 Publication1
Mutagenesisi610D → V: Abolishes regulation by micromolar Ca(2+). 1 Publication1
Mutagenesisi617K → E: Decreases affinity for Ca(2+), but retains regulation by micromolar Ca(2+). 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000001937633 – 970Sodium/calcium exchanger 1Add BLAST938

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi41N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi157N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei282PhosphoserineBy similarity1
Modified residuei389PhosphoserineSequence analysisBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP23685

PTM databases

iPTMnetiP23685
SwissPalmiP23685

Expressioni

Tissue specificityi

Cardiac sarcolemma (at protein level).1 Publication

Gene expression databases

BgeeiENSCAFG00000023592 Expressed in 3 organ(s), highest expression level in prefrontal cortex

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-59598N
STRINGi9615.ENSCAFP00000009692

Structurei

Secondary structure

1970
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP23685
SMRiP23685
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23685

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 region1 PublicationAdd 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 (PubMed:16774926, PubMed:19332552, PubMed:22768191). The second domain can bind another two Ca2+ ions that are essential for calcium-regulated ion exchange (PubMed:17962412).4 Publications

Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1306 Eukaryota
ENOG410XPJP LUCA
GeneTreeiENSGT00730000110414
HOGENOMiHOG000266971
HOVERGENiHBG006441
InParanoidiP23685
KOiK05849
OMAiTVYVDFR
OrthoDBiEOG091G0EC1
TreeFamiTF314308

Family and domain databases

Gene3Di2.60.40.2030, 1 hit
InterProiView protein in InterPro
IPR038081 CalX-like_sf
IPR003644 Calx_beta
IPR001623 DnaJ_domain
IPR004836 Na_Ca_Ex
IPR032452 Na_Ca_Ex_C-exten
IPR002987 NaCa_exhngr1
IPR004837 NaCa_Exmemb
PfamiView protein in Pfam
PF03160 Calx-beta, 2 hits
PF01699 Na_Ca_ex, 2 hits
PF16494 Na_Ca_ex_C, 1 hit
PRINTSiPR01259 NACAEXCHNGR
PR01260 NACAEXCHNGR1
SMARTiView protein in SMART
SM00237 Calx_beta, 2 hits
SUPFAMiSSF141072 SSF141072, 2 hits
TIGRFAMsiTIGR00845 caca, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P23685-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLQLRLLPTF SMGCHLLAVV ALLFSHVDLI SAETEMEGEG NETGECTGSY
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 VISPGVVEVW EGLLTFFFFP ICVVFAWVAD
260 270 280 290 300
RRLLFYKYVY KRYRAGKQRG MIIEHEGDRP SSKTEIEMDG KVVNSHVDNF
310 320 330 340 350
LDGALVLEVD ERDQDDEEAR REMARILKEL KQKHPEKEIE QLIELANYQV
360 370 380 390 400
LSQQQKSRAF YRIQATRLMT GAGNILKRHA ADQARKAVSM HEVNTEVAEN
410 420 430 440 450
DPVSKIFFEQ GTYQCLENCG TVALTIIRRG GDLTNTVFVD FRTEDGTANA
460 470 480 490 500
GSDYEFTEGT VVFKPGETQK EIRVGIIDDD IFEEDENFLV HLSNVKVSSE
510 520 530 540 550
ASEDGILEAN HVSALACLGS PSTATVTIFD DDHAGIFTFE EPVTHVSESI
560 570 580 590 600
GIMEVKVLRT SGARGNVIVP YKTIEGTARG GGEDFEDTCG ELEFQNDEIV
610 620 630 640 650
KTISVKVIDD EEYEKNKTFF LEIGEPRLVE MSEKKALLLN ELGGFTITGK
660 670 680 690 700
YLYGQPVFRK VHAREHPIPS TVITIAEEYD DKQPLTSKEE EERRIAEMGR
710 720 730 740 750
PILGEHTKLE VIIEESYEFK STVDKLIKKT NLALVVGTNS WREQFIEAIT
760 770 780 790 800
VSAGEDDDDD ECGEEKLPSC FDYVMHFLTV FWKVLFAFVP PTEYWNGWAC
810 820 830 840 850
FIVSILMIGI LTAFIGDLAS HFGCTIGLKD SVTAVVFVAL GTSVPDTFAS
860 870 880 890 900
KVAATQDQYA DASIGNVTGS NAVNVFLGIG VAWSIAAIYH AANGEQFKVS
910 920 930 940 950
PGTLAFSVTL FTIFAFINVG VLLYRRRPEI GGELGGPRTA KLLTSCLFVL
960 970
LWLLYIFFSS LEAYCHIKGF
Length:970
Mass (Da):108,004
Last modified:November 1, 1991 - v1
Checksum:iBBDBCC584846AE08
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F1PHW1F1PHW1_CANLF
Sodium/calcium exchanger 1
SLC8A1
335Annotation score:
F1PHW2F1PHW2_CANLF
Sodium/calcium exchanger 1
SLC8A1
365Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M57523 mRNA Translation: AAA62766.1
PIRiA36417
RefSeqiNP_001291891.1, NM_001304962.1
XP_013975680.1, XM_014120205.1
XP_013975681.1, XM_014120206.1
XP_013975682.1, XM_014120207.1
XP_013975683.1, XM_014120208.1
XP_013975684.1, XM_014120209.1
XP_013975685.1, XM_014120210.1
XP_013975686.1, XM_014120211.1
XP_013975687.1, XM_014120212.1
XP_013975688.1, XM_014120213.1
XP_013975689.1, XM_014120214.1

Genome annotation databases

EnsembliENSCAFT00000010451; ENSCAFP00000009692; ENSCAFG00000023592
GeneIDi475738
KEGGicfa:475738

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M57523 mRNA Translation: AAA62766.1
PIRiA36417
RefSeqiNP_001291891.1, NM_001304962.1
XP_013975680.1, XM_014120205.1
XP_013975681.1, XM_014120206.1
XP_013975682.1, XM_014120207.1
XP_013975683.1, XM_014120208.1
XP_013975684.1, XM_014120209.1
XP_013975685.1, XM_014120210.1
XP_013975686.1, XM_014120211.1
XP_013975687.1, XM_014120212.1
XP_013975688.1, XM_014120213.1
XP_013975689.1, XM_014120214.1

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DPKX-ray2.50A402-541[»]
2FWSNMR-A403-541[»]
2FWUNMR-A533-724[»]
2QVKX-ray1.45A533-721[»]
2QVMX-ray1.70A533-721[»]
3GINX-ray2.40A/B402-541[»]
3US9X-ray2.68A403-724[»]
6BV7NMR-A306-359[»]
ProteinModelPortaliP23685
SMRiP23685
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59598N
STRINGi9615.ENSCAFP00000009692

PTM databases

iPTMnetiP23685
SwissPalmiP23685

Proteomic databases

PaxDbiP23685

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCAFT00000010451; ENSCAFP00000009692; ENSCAFG00000023592
GeneIDi475738
KEGGicfa:475738

Organism-specific databases

CTDi6546
VGNCiVGNC:46480 SLC8A1

Phylogenomic databases

eggNOGiKOG1306 Eukaryota
ENOG410XPJP LUCA
GeneTreeiENSGT00730000110414
HOGENOMiHOG000266971
HOVERGENiHBG006441
InParanoidiP23685
KOiK05849
OMAiTVYVDFR
OrthoDBiEOG091G0EC1
TreeFamiTF314308

Enzyme and pathway databases

ReactomeiR-CFA-418359 Reduction of cytosolic Ca++ levels
R-CFA-425561 Sodium/Calcium exchangers
R-CFA-5578775 Ion homeostasis

Miscellaneous databases

EvolutionaryTraceiP23685

Gene expression databases

BgeeiENSCAFG00000023592 Expressed in 3 organ(s), highest expression level in prefrontal cortex

Family and domain databases

Gene3Di2.60.40.2030, 1 hit
InterProiView protein in InterPro
IPR038081 CalX-like_sf
IPR003644 Calx_beta
IPR001623 DnaJ_domain
IPR004836 Na_Ca_Ex
IPR032452 Na_Ca_Ex_C-exten
IPR002987 NaCa_exhngr1
IPR004837 NaCa_Exmemb
PfamiView protein in Pfam
PF03160 Calx-beta, 2 hits
PF01699 Na_Ca_ex, 2 hits
PF16494 Na_Ca_ex_C, 1 hit
PRINTSiPR01259 NACAEXCHNGR
PR01260 NACAEXCHNGR1
SMARTiView protein in SMART
SM00237 Calx_beta, 2 hits
SUPFAMiSSF141072 SSF141072, 2 hits
TIGRFAMsiTIGR00845 caca, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNAC1_CANLF
AccessioniPrimary (citable) accession number: P23685
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: November 7, 2018
This is version 139 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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