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Protein

Sodium/calcium exchanger 1

Gene

SLC8A1

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
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: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

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

GO - Molecular functioni

  • calcium:sodium antiporter activity Source: UniProtKB
  • calcium ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

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

Keywords - Ligandi

Calcium, Calmodulin-binding, 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

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 – 797548CytoplasmicCuratedAdd
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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi548 – 5481E → L: Abolishes regulation by micromolar Ca(2+). 1 Publication
Mutagenesisi584 – 5841D → V: No effect on regulation by micromolar Ca(2+). 1 Publication
Mutagenesisi610 – 6101D → V: Abolishes regulation by micromolar Ca(2+). 1 Publication
Mutagenesisi617 – 6171K → E: Decreases affinity for Ca(2+), but retains regulation by micromolar Ca(2+). 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence analysisAdd
BLAST
Chaini33 – 970938Sodium/calcium exchanger 1PRO_0000019376Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP23685.

Expressioni

Tissue specificityi

Cardiac sarcolemma (at protein level).1 Publication

Interactioni

Protein-protein interaction databases

DIPiDIP-59598N.
STRINGi9615.ENSCAFP00000009692.

Structurei

Secondary structure

1
970
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi403 – 4097Combined sources
Beta strandi411 – 4166Combined sources
Beta strandi419 – 43113Combined sources
Beta strandi437 – 44812Combined sources
Turni450 – 4523Combined sources
Beta strandi458 – 4636Combined sources
Beta strandi469 – 4768Combined sources
Beta strandi486 – 49611Combined sources
Beta strandi515 – 5184Combined sources
Beta strandi522 – 5298Combined sources
Beta strandi536 – 5405Combined sources
Beta strandi542 – 5476Combined sources
Beta strandi552 – 56110Combined sources
Beta strandi567 – 57812Combined sources
Turni580 – 5834Combined sources
Beta strandi584 – 5863Combined sources
Beta strandi589 – 5946Combined sources
Beta strandi600 – 6078Combined sources
Beta strandi615 – 6239Combined sources
Beta strandi627 – 6293Combined sources
Helixi687 – 69610Combined sources
Beta strandi708 – 7147Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP23685.
SMRiP23685. Positions 403-724.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23685.

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 region1 PublicationAdd
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 (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

Contains 2 Calx-beta domains.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiP23685.
KOiK05849.
OMAiDDEECGE.
OrthoDBiEOG7S4X56.
TreeFamiTF314308.

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.

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

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.

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
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[»]
ProteinModelPortaliP23685.
SMRiP23685. Positions 403-724.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59598N.
STRINGi9615.ENSCAFP00000009692.

Proteomic databases

PaxDbiP23685.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCAFT00000010451; ENSCAFP00000009692; ENSCAFG00000023592.
GeneIDi475738.
KEGGicfa:475738.

Organism-specific databases

CTDi6546.

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiP23685.
KOiK05849.
OMAiDDEECGE.
OrthoDBiEOG7S4X56.
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.

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

  1. "Molecular cloning and functional expression of the cardiac sarcolemmal Na(+)-Ca2+ exchanger."
    Nicoll D.A., Longoni S., Philipson K.D.
    Science 250:562-565(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Heart.
  2. "Molecular studies of the cardiac sarcolemmal sodium-calcium exchanger."
    Nicoll D.A., Philipson K.D.
    Ann. N. Y. Acad. Sci. 639:181-188(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
    Tissue: Heart.
  3. "Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3)."
    Linck B., Qiu Z., He Z., Tong Q., Hilgemann D.W., Philipson K.D.
    Am. J. Physiol. 274:C415-C423(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
  4. "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.
  5. "The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif."
    Nicoll D.A., Sawaya M.R., Kwon S., Cascio D., Philipson K.D., Abramson J.
    J. Biol. Chem. 281:21577-21581(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 402-541 IN COMPLEX WITH CALCIUM, CALCIUM-BINDING SITES, DOMAIN.
  6. "The second Ca2+-binding domain of the Na+ Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis."
    Besserer G.M., Ottolia M., Nicoll D.A., Chaptal V., Cascio D., Philipson K.D., Abramson J.
    Proc. Natl. Acad. Sci. U.S.A. 104:18467-18472(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 533-721 ALONE AND IN COMPLEX WITH CALCIUM IONS, CALCIUM-BINDING SITES, FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, MUTAGENESIS OF GLU-548; ASP-584; ASP-610 AND LYS-617.
  7. "Structure and functional analysis of a Ca2+ sensor mutant of the Na+/Ca2+ exchanger."
    Chaptal V., Ottolia M., Mercado-Besserer G., Nicoll D.A., Philipson K.D., Abramson J.
    J. Biol. Chem. 284:14688-14692(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 402-541 IN COMPLEX WITH CALCIUM, FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, DOMAIN.
  8. "A common Ca2+-driven interdomain module governs eukaryotic NCX regulation."
    Giladi M., Sasson Y., Fang X., Hiller R., Buki T., Wang Y.X., Hirsch J.A., Khananshvili D.
    PLoS ONE 7:E39985-E39985(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF 403-724 IN COMPLEX WITH CALCIUM, DOMAIN.

Entry informationi

Entry nameiNAC1_CANLF
AccessioniPrimary (citable) accession number: P23685
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: May 11, 2016
This is version 125 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.