UniProtKB - P23685 (NAC1_CANLF)
Protein
Sodium/calcium exchanger 1
Gene
SLC8A1
Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 417 | Calcium 1Combined sources | 1 | |
Metal bindingi | 417 | Calcium 2Combined sources | 1 | |
Metal bindingi | 417 | Calcium 3Combined sources | 1 | |
Metal bindingi | 453 | Calcium 1Combined sources | 1 | |
Metal bindingi | 453 | Calcium 4Combined sources | 1 | |
Metal bindingi | 478 | Calcium 2Combined sources | 1 | |
Metal bindingi | 479 | Calcium 1Combined sources | 1 | |
Metal bindingi | 479 | Calcium 2; via carbonyl oxygenCombined sources | 1 | |
Metal bindingi | 479 | Calcium 3Combined sources | 1 | |
Metal bindingi | 479 | Calcium 4Combined sources | 1 | |
Metal bindingi | 481 | Calcium 3; via carbonyl oxygenCombined sources | 1 | |
Metal bindingi | 483 | Calcium 1Combined sources | 1 | |
Metal bindingi | 483 | Calcium 3Combined sources | 1 | |
Metal bindingi | 483 | Calcium 4Combined sources | 1 | |
Metal bindingi | 486 | Calcium 4Combined sources | 1 | |
Metal bindingi | 530 | Calcium 3Combined sources | 1 | |
Metal bindingi | 531 | Calcium 2Combined sources | 1 | |
Metal bindingi | 532 | Calcium 2Combined sources | 1 | |
Metal bindingi | 532 | Calcium 3Combined sources | 1 | |
Metal bindingi | 548 | Calcium 5Combined sources | 1 | |
Metal bindingi | 584 | Calcium 6Combined sources | 1 | |
Metal bindingi | 610 | Calcium 5Combined sources | 1 | |
Metal bindingi | 610 | Calcium 6Combined sources | 1 | |
Metal bindingi | 611 | Calcium 6Combined sources | 1 | |
Metal bindingi | 612 | Calcium 5; via carbonyl oxygenCombined sources | 1 | |
Metal bindingi | 612 | Calcium 6Combined sources | 1 | |
Metal bindingi | 715 | Calcium 5Combined sources | 1 |
GO - Molecular functioni
- ankyrin binding Source: Ensembl
- calcium:cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration Source: SynGO
- calcium:sodium antiporter activity Source: UniProtKB
- calcium ion binding Source: UniProtKB
- calmodulin binding Source: UniProtKB-KW
- cation:cation antiporter activity Source: GO_Central
GO - Biological processi
- calcium ion import across plasma membrane Source: GO_Central
- calcium ion transmembrane transport Source: UniProtKB
- cell communication Source: InterPro
- cellular sodium ion homeostasis Source: Ensembl
- metal ion transport Source: GO_Central
- positive regulation of bone mineralization Source: Ensembl
- positive regulation of the force of heart contraction Source: Ensembl
- response to muscle stretch Source: Ensembl
- sodium ion import across plasma membrane Source: Ensembl
- sodium ion transmembrane transport Source: UniProtKB
Keywordsi
Molecular function | Calmodulin-binding |
Biological process | Antiport, Calcium transport, Ion transport, Sodium transport, Transport |
Ligand | Calcium, Metal-binding, Sodium |
Enzyme and pathway databases
Reactomei | R-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 1Alternative name(s): Na(+)/Ca(2+)-exchange protein 1 Solute carrier family 8 member 1 |
Gene namesi | Name:SLC8A1 Synonyms:NCX11 Publication |
Organismi | Canis lupus familiaris (Dog) (Canis familiaris) |
Taxonomic identifieri | 9615 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane 5 Publications; Multi-pass membrane protein Curated
- sarcolemma 1 Publication
Nucleus
- nucleoplasm Source: Ensembl
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- intrinsic component of plasma membrane Source: UniProtKB
- sarcolemma Source: GO_Central
Other locations
- axon Source: GO_Central
- membrane Source: GO_Central
- postsynapse Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 33 – 71 | ExtracellularSequence analysisAdd BLAST | 39 | |
Transmembranei | 72 – 92 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 93 – 133 | CytoplasmicSequence analysisAdd BLAST | 41 | |
Transmembranei | 134 – 154 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 155 – 167 | ExtracellularSequence analysisAdd BLAST | 13 | |
Transmembranei | 168 – 188 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 189 – 201 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Transmembranei | 202 – 222 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 223 – 228 | ExtracellularSequence analysis | 6 | |
Transmembranei | 229 – 249 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 250 – 797 | CytoplasmicCuratedAdd BLAST | 548 | |
Transmembranei | 798 – 818 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 819 – 821 | ExtracellularSequence analysis | 3 | |
Transmembranei | 822 – 842 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 843 – 871 | CytoplasmicSequence analysisAdd BLAST | 29 | |
Transmembranei | 872 – 892 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 893 – 903 | ExtracellularSequence analysisAdd BLAST | 11 | |
Transmembranei | 904 – 924 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 925 – 941 | CytoplasmicSequence analysisAdd BLAST | 17 | |
Transmembranei | 942 – 962 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 963 – 970 | ExtracellularSequence analysis | 8 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 548 | E → L: Abolishes regulation by micromolar Ca(2+). 1 Publication | 1 | |
Mutagenesisi | 584 | D → V: No effect on regulation by micromolar Ca(2+). 1 Publication | 1 | |
Mutagenesisi | 610 | D → V: Abolishes regulation by micromolar Ca(2+). 1 Publication | 1 | |
Mutagenesisi | 617 | K → E: Decreases affinity for Ca(2+), but retains regulation by micromolar Ca(2+). 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 32 | Sequence analysisAdd BLAST | 32 | |
ChainiPRO_0000019376 | 33 – 970 | Sodium/calcium exchanger 1Add BLAST | 938 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 41 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 157 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 282 | PhosphoserineBy similarity | 1 | |
Modified residuei | 389 | PhosphoserineSequence analysisBy similarity | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | P23685 |
PTM databases
iPTMneti | P23685 |
SwissPalmi | P23685 |
Expressioni
Tissue specificityi
Cardiac sarcolemma (at protein level).1 Publication
Gene expression databases
Bgeei | ENSCAFG00000023592, Expressed in cardiac muscle of left ventricle and 50 other tissues |
Interactioni
GO - Molecular functioni
- ankyrin binding Source: Ensembl
- calmodulin binding Source: UniProtKB-KW
Protein-protein interaction databases
DIPi | DIP-59598N |
STRINGi | 9612.ENSCAFP00000009692 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P23685 |
SMRi | P23685 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P23685 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 138 – 178 | Alpha-1Add BLAST | 41 | |
Domaini | 393 – 493 | Calx-beta 1Add BLAST | 101 | |
Domaini | 524 – 624 | Calx-beta 2Add BLAST | 101 | |
Repeati | 839 – 875 | Alpha-2Add BLAST | 37 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 251 – 270 | Putative calmodulin-binding region1 PublicationAdd BLAST | 20 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 236 – 239 | Poly-Phe | 4 | |
Compositional biasi | 689 – 692 | Poly-Glu | 4 | |
Compositional biasi | 756 – 760 | Poly-Asp | 5 |
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
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily. [View classification]Curated
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1306, Eukaryota |
HOGENOMi | CLU_012872_1_0_1 |
InParanoidi | P23685 |
OMAi | HFICLFW |
OrthoDBi | 490546at2759 |
TreeFami | TF314308 |
Family and domain databases
Gene3Di | 2.60.40.2030, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF03160, Calx-beta, 2 hits PF01699, Na_Ca_ex, 2 hits PF16494, Na_Ca_ex_C, 1 hit |
PRINTSi | PR01259, NACAEXCHNGR PR01260, NACAEXCHNGR1 |
SMARTi | View protein in SMART SM00237, Calx_beta, 2 hits |
SUPFAMi | SSF141072, SSF141072, 2 hits |
TIGRFAMsi | TIGR00845, caca, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P23685-1 [UniParc]FASTAAdd to basket
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
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M57523 mRNA Translation: AAA62766.1 |
PIRi | A36417 |
RefSeqi | NP_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
GeneIDi | 475738 |
KEGGi | cfa:475738 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M57523 mRNA Translation: AAA62766.1 |
PIRi | A36417 |
RefSeqi | NP_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 entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2DPK | X-ray | 2.50 | A | 402-541 | [»] | |
2FWS | NMR | - | A | 403-541 | [»] | |
2FWU | NMR | - | A | 533-724 | [»] | |
2QVK | X-ray | 1.45 | A | 533-721 | [»] | |
2QVM | X-ray | 1.70 | A | 533-721 | [»] | |
3GIN | X-ray | 2.40 | A/B | 402-541 | [»] | |
3US9 | X-ray | 2.68 | A | 403-724 | [»] | |
6BV7 | NMR | - | A | 306-359 | [»] | |
BMRBi | P23685 | |||||
SMRi | P23685 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
DIPi | DIP-59598N |
STRINGi | 9612.ENSCAFP00000009692 |
PTM databases
iPTMneti | P23685 |
SwissPalmi | P23685 |
Proteomic databases
PaxDbi | P23685 |
Genome annotation databases
GeneIDi | 475738 |
KEGGi | cfa:475738 |
Organism-specific databases
CTDi | 6546 |
Phylogenomic databases
eggNOGi | KOG1306, Eukaryota |
HOGENOMi | CLU_012872_1_0_1 |
InParanoidi | P23685 |
OMAi | HFICLFW |
OrthoDBi | 490546at2759 |
TreeFami | TF314308 |
Enzyme and pathway databases
Reactomei | R-CFA-418359, Reduction of cytosolic Ca++ levels R-CFA-425561, Sodium/Calcium exchangers R-CFA-5578775, Ion homeostasis |
Miscellaneous databases
EvolutionaryTracei | P23685 |
Gene expression databases
Bgeei | ENSCAFG00000023592, Expressed in cardiac muscle of left ventricle and 50 other tissues |
Family and domain databases
Gene3Di | 2.60.40.2030, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF03160, Calx-beta, 2 hits PF01699, Na_Ca_ex, 2 hits PF16494, Na_Ca_ex_C, 1 hit |
PRINTSi | PR01259, NACAEXCHNGR PR01260, NACAEXCHNGR1 |
SMARTi | View protein in SMART SM00237, Calx_beta, 2 hits |
SUPFAMi | SSF141072, SSF141072, 2 hits |
TIGRFAMsi | TIGR00845, caca, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NAC1_CANLF | |
Accessioni | P23685Primary (citable) accession number: P23685 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1991 |
Last sequence update: | November 1, 1991 | |
Last modified: | December 2, 2020 | |
This is version 152 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families