UniProtKB - P32418 (NAC1_HUMAN)
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Protein
Sodium/calcium exchanger 1
Gene
SLC8A1
Organism
Homo sapiens (Human)
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:1374913, PubMed:11241183, PubMed:1476165). 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 similarity3 Publications
Enzyme regulationi
Activated by micromolar levels of Ca2+.Curated
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 420 | Calcium 1By similarity | 1 | |
Metal bindingi | 420 | Calcium 2By similarity | 1 | |
Metal bindingi | 420 | Calcium 3By similarity | 1 | |
Metal bindingi | 456 | Calcium 1By similarity | 1 | |
Metal bindingi | 456 | Calcium 4By similarity | 1 | |
Metal bindingi | 481 | Calcium 2By similarity | 1 | |
Metal bindingi | 482 | Calcium 1By similarity | 1 | |
Metal bindingi | 482 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 482 | Calcium 3By similarity | 1 | |
Metal bindingi | 482 | Calcium 4By similarity | 1 | |
Metal bindingi | 484 | Calcium 3; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 486 | Calcium 1By similarity | 1 | |
Metal bindingi | 486 | Calcium 3By similarity | 1 | |
Metal bindingi | 486 | Calcium 4By similarity | 1 | |
Metal bindingi | 489 | Calcium 4By similarity | 1 | |
Metal bindingi | 533 | Calcium 3By similarity | 1 | |
Metal bindingi | 534 | Calcium 2By similarity | 1 | |
Metal bindingi | 535 | Calcium 2By similarity | 1 | |
Metal bindingi | 535 | Calcium 3By similarity | 1 | |
Metal bindingi | 551 | Calcium 5By similarity | 1 | |
Metal bindingi | 587 | Calcium 6By similarity | 1 | |
Metal bindingi | 613 | Calcium 5By similarity | 1 | |
Metal bindingi | 613 | Calcium 6By similarity | 1 | |
Metal bindingi | 614 | Calcium 6By similarity | 1 | |
Metal bindingi | 615 | Calcium 5; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 615 | Calcium 6By similarity | 1 | |
Metal bindingi | 718 | Calcium 5By similarity | 1 |
GO - Molecular functioni
- ankyrin binding Source: BHF-UCL
- calcium:sodium antiporter activity Source: BHF-UCL
- calcium ion binding Source: UniProtKB
- calmodulin binding Source: UniProtKB-KW
- cytoskeletal protein binding Source: BHF-UCL
- ion antiporter activity involved in regulation of postsynaptic membrane potential Source: Ensembl
- 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 into cytosol Source: BHF-UCL
- cardiac muscle cell development Source: BHF-UCL
- cardiac muscle contraction Source: BHF-UCL
- cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
- cellular response to caffeine Source: BHF-UCL
- cellular response to cAMP Source: Ensembl
- cellular response to hypoxia Source: Ensembl
- cellular response to reactive oxygen species Source: BHF-UCL
- cellular sodium ion homeostasis Source: BHF-UCL
- cytosolic calcium ion transport Source: BHF-UCL
- ion transport Source: Reactome
- membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
- muscle contraction Source: ProtInc
- negative regulation of cytosolic calcium ion concentration Source: BHF-UCL
- positive regulation of bone mineralization Source: UniProtKB
- positive regulation of fibroblast migration Source: Ensembl
- positive regulation of the force of heart contraction Source: BHF-UCL
- regulation of cardiac conduction Source: Reactome
- regulation of cardiac muscle contraction by calcium ion signaling Source: BHF-UCL
- regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
- regulation of cell communication by electrical coupling Source: BHF-UCL
- regulation of heart rate Source: BHF-UCL
- regulation of sodium ion transport Source: Ensembl
- regulation of the force of heart contraction Source: BHF-UCL
- relaxation of cardiac muscle Source: BHF-UCL
- relaxation of smooth muscle Source: BHF-UCL
- response to ATP Source: Ensembl
- response to glucose Source: Ensembl
- response to hydrogen peroxide Source: Ensembl
- response to immobilization stress Source: Ensembl
- response to muscle stretch Source: BHF-UCL
- sodium ion export across plasma membrane Source: BHF-UCL
- sodium ion import across plasma membrane Source: BHF-UCL
- sodium ion transmembrane transport Source: UniProtKB
- telencephalon development Source: Ensembl
- vascular smooth muscle contraction Source: BHF-UCL
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-HSA-418359 Reduction of cytosolic Ca++ levels R-HSA-425561 Sodium/Calcium exchangers R-HSA-5578775 Ion homeostasis |
Protein family/group databases
TCDBi | 2.A.19.3.4 the ca(2+):cation antiporter (caca) family |
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:CNC, NCX12 Publications |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000183023.18 |
HGNCi | HGNC:11068 SLC8A1 |
MIMi | 182305 gene |
neXtProti | NX_P32418 |
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 36 – 74 | ExtracellularSequence analysisAdd BLAST | 39 | |
Transmembranei | 75 – 95 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 96 – 136 | CytoplasmicSequence analysisAdd BLAST | 41 | |
Transmembranei | 137 – 157 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 158 – 170 | ExtracellularSequence analysisAdd BLAST | 13 | |
Transmembranei | 171 – 191 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 192 – 204 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Transmembranei | 205 – 225 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 226 – 231 | ExtracellularSequence analysis | 6 | |
Transmembranei | 232 – 252 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 253 – 800 | CytoplasmicSequence analysisAdd BLAST | 548 | |
Transmembranei | 801 – 821 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 822 – 824 | ExtracellularSequence analysis | 3 | |
Transmembranei | 825 – 845 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 846 – 874 | CytoplasmicSequence analysisAdd BLAST | 29 | |
Transmembranei | 875 – 895 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 896 – 906 | ExtracellularSequence analysisAdd BLAST | 11 | |
Transmembranei | 907 – 927 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 928 – 944 | CytoplasmicSequence analysisAdd BLAST | 17 | |
Transmembranei | 945 – 965 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 966 – 973 | ExtracellularSequence analysis | 8 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 6546 |
OpenTargetsi | ENSG00000183023 |
PharmGKBi | PA314 |
Chemistry databases
ChEMBLi | CHEMBL4076 |
DrugBanki | DB00132 Alpha-Linolenic Acid DB00159 Icosapent |
Polymorphism and mutation databases
BioMutai | SLC8A1 |
DMDMi | 12644210 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 35 | Sequence analysisAdd BLAST | 35 | |
ChainiPRO_0000019379 | 36 – 973 | Sodium/calcium exchanger 1Add BLAST | 938 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 44 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 160 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 285 | PhosphoserineBy similarity | 1 | |
Modified residuei | 392 | PhosphoserineSequence analysisBy similarity | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | P32418 |
PeptideAtlasi | P32418 |
PRIDEi | P32418 |
PTM databases
iPTMneti | P32418 |
PhosphoSitePlusi | P32418 |
Expressioni
Tissue specificityi
Detected primarily in heart and at lower levels in brain (PubMed:1374913). Expressed in cardiac sarcolemma, brain, kidney, liver, pancreas, skeletal muscle, placenta and lung (PubMed:1476165).2 Publications
Gene expression databases
Bgeei | ENSG00000183023 |
CleanExi | HS_SLC8A1 |
ExpressionAtlasi | P32418 baseline and differential |
Genevisiblei | P32418 HS |
Organism-specific databases
HPAi | CAB022694 HPA070007 |
Interactioni
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
ANK2 | Q01484-2 | 2 | EBI-2682189,EBI-941994 |
GO - Molecular functioni
- ankyrin binding Source: BHF-UCL
- calmodulin binding Source: UniProtKB-KW
- cytoskeletal protein binding Source: BHF-UCL
- ion channel binding Source: BHF-UCL
Protein-protein interaction databases
BioGridi | 1124361 interactor. |
DIPi | DIP-48356N |
ELMi | P32418 |
IntActi | P32418 2 interactors. |
STRINGi | 9606.ENSP00000332931 |
Chemistry databases
BindingDBi | P32418 |
Structurei
3D structure databases
ProteinModelPortali | P32418 |
SMRi | P32418 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 141 – 181 | Alpha-1Add BLAST | 41 | |
Domaini | 396 – 496 | Calx-beta 1Add BLAST | 101 | |
Domaini | 527 – 627 | Calx-beta 2Add BLAST | 101 | |
Repeati | 842 – 878 | Alpha-2Add BLAST | 37 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 254 – 273 | Putative calmodulin-binding regionBy similarityAdd BLAST | 20 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 239 – 242 | Poly-Phe | 4 | |
Compositional biasi | 692 – 695 | Poly-Glu | 4 | |
Compositional biasi | 759 – 763 | 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. The second domain can bind another two Ca2+ ions that are essential for calcium-regulated ion exchange.By similarity
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 ENOG410XPJP LUCA |
GeneTreei | ENSGT00730000110414 |
HOGENOMi | HOG000266971 |
HOVERGENi | HBG006441 |
InParanoidi | P32418 |
KOi | K05849 |
OMAi | TVYVDFR |
OrthoDBi | EOG091G0EC1 |
PhylomeDBi | P32418 |
TreeFami | TF314308 |
Family and domain databases
Gene3Di | 2.60.40.20301 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, 3 hits |
TIGRFAMsi | TIGR00845 caca, 1 hit |
s (5)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P32418-1) [UniParc]FASTAAdd to basket
Also known as: NaCa1, NCX1.1
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT
60 70 80 90 100
GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMFL GVSIIADRFM
110 120 130 140 150
SSIEVITSQE KEITIKKPNG ETTKTTVRIW NETVSNLTLM ALGSSAPEIL
160 170 180 190 200
LSVIEVCGHN FTAGDLGPST IVGSAAFNMF IIIALCVYVV PDGETRKIKH
210 220 230 240 250
LRVFFVTAAW SIFAYTWLYI ILSVISPGVV EVWEGLLTFF FFPICVVFAW
260 270 280 290 300
VADRRLLFYK YVYKRYRAGK QRGMIIEHEG DRPSSKTEIE MDGKVVNSHV
310 320 330 340 350
ENFLDGALVL EVDERDQDDE EARREMARIL KELKQKHPDK EIEQLIELAN
360 370 380 390 400
YQVLSQQQKS RAFYRIQATR LMTGAGNILK RHAADQARKA VSMHEVNTEV
410 420 430 440 450
TENDPVSKIF FEQGTYQCLE NCGTVALTII RRGGDLTNTV FVDFRTEDGT
460 470 480 490 500
ANAGSDYEFT EGTVVFKPGD TQKEIRVGII DDDIFEEDEN FLVHLSNVKV
510 520 530 540 550
SSEASEDGIL EANHVSTLAC LGSPSTATVT IFDDDHAGIF TFEEPVTHVS
560 570 580 590 600
ESIGIMEVKV LRTSGARGNV IVPYKTIEGT ARGGGEDFED TCGELEFQND
610 620 630 640 650
EIVKTISVKV IDDEEYEKNK TFFLEIGEPR LVEMSEKKAL LLNELGGFTI
660 670 680 690 700
TGKYLFGQPV FRKVHAREHP ILSTVITIAD EYDDKQPLTS KEEEERRIAE
710 720 730 740 750
MGRPILGEHT KLEVIIEESY EFKSTVDKLI KKTNLALVVG TNSWREQFIE
760 770 780 790 800
AITVSAGEDD DDDECGEEKL PSCFDYVMHF LTVFWKVLFA FVPPTEYWNG
810 820 830 840 850
WACFIVSILM IGLLTAFIGD LASHFGCTIG LKDSVTAVVF VALGTSVPDT
860 870 880 890 900
FASKVAATQD QYADASIGNV TGSNAVNVFL GIGVAWSIAA IYHAANGEQF
910 920 930 940 950
KVSPGTLAFS VTLFTIFAFI NVGVLLYRRR PEIGGELGGP RTAKLLTSCL
960 970
FVLLWLLYIF FSSLEAYCHI KGF
Isoform 10 (identifier: P32418-4) [UniParc]FASTAAdd to basket
Also known as: NaCa10, NCX1.10
The sequence of this isoform differs from the canonical sequence as follows:
605-613: TISVKVIDD → IITIRIFDR
619-645: NKTFFLEIGEPRLVEMSEKKALLLNEL → ECSFSLVLEEPKWIRRGMK
Sequence cautioni
The sequence AAH98308 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014847 | 692 | E → V. Corresponds to variant dbSNP:rs5557Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_003397 | 605 – 613 | TISVKVIDD → IITIRIFDR in isoform 3, isoform 7 and isoform 10. 5 Publications | 9 | |
Alternative sequenceiVSP_003398 | 619 – 645 | NKTFF…LLNEL → ECSFSLVLEEPKWIRRGMK in isoform 3, isoform 7 and isoform 10. 5 PublicationsAdd BLAST | 27 | |
Alternative sequenceiVSP_003400 | 652 – 679 | Missing in isoform 3. 3 PublicationsAdd BLAST | 28 | |
Alternative sequenceiVSP_003399 | 652 – 656 | Missing in isoform 7 and isoform 5. 4 Publications | 5 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | NAC1_HUMAN | |
Accessioni | P32418Primary (citable) accession number: P32418 Secondary accession number(s): A8K6N1 Q9UKX6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1993 |
Last sequence update: | December 1, 2000 | |
Last modified: | April 25, 2018 | |
This is version 177 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |