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Protein

Sodium/calcium exchanger 2

Gene

Slc8a2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates the electrogenic exchange of Ca2+ against Na+ ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca2+ levels and Ca2+-dependent cellular processes. Contributes to cellular Ca2+ homeostasis in excitable cells. Contributes to the rapid decrease of cytoplasmic Ca2+ levels back to baseline after neuronal activation, and thereby contributes to modulate synaptic plasticity, learning and memory (PubMed:12818181). Plays a role in regulating urinary Ca2+ and Na+ excretion (PubMed:25498502).1 Publication

Enzyme regulationi

Calcium transport is down-regulated by Na+ and stimulated by Ca2+.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi407 – 4071Calcium 1By similarity
Metal bindingi407 – 4071Calcium 2By similarity
Metal bindingi407 – 4071Calcium 3By similarity
Metal bindingi443 – 4431Calcium 1By similarity
Metal bindingi443 – 4431Calcium 4By similarity
Metal bindingi468 – 4681Calcium 2By similarity
Metal bindingi469 – 4691Calcium 1By similarity
Metal bindingi469 – 4691Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi469 – 4691Calcium 3By similarity
Metal bindingi469 – 4691Calcium 4By similarity
Metal bindingi471 – 4711Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi473 – 4731Calcium 1By similarity
Metal bindingi473 – 4731Calcium 3By similarity
Metal bindingi473 – 4731Calcium 4By similarity
Metal bindingi476 – 4761Calcium 4By similarity
Metal bindingi518 – 5181Calcium 3By similarity
Metal bindingi519 – 5191Calcium 2By similarity
Metal bindingi520 – 5201Calcium 2By similarity
Metal bindingi520 – 5201Calcium 3By similarity
Metal bindingi536 – 5361Calcium 5By similarity
Metal bindingi598 – 5981Calcium 5By similarity
Metal bindingi598 – 5981Calcium 6By similarity
Metal bindingi599 – 5991Calcium 6By similarity
Metal bindingi600 – 6001Calcium 5; via carbonyl oxygenBy similarity
Metal bindingi600 – 6001Calcium 6By similarity
Metal bindingi665 – 6651Calcium 5By similarity

GO - Molecular functioni

  • calcium:sodium antiporter activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • calcium ion transmembrane transport Source: UniProtKB
  • cell communication Source: InterPro
  • cellular calcium ion homeostasis Source: UniProtKB
  • learning Source: UniProtKB
  • long-term synaptic potentiation Source: UniProtKB
  • memory Source: UniProtKB
  • regulation of short-term neuronal synaptic plasticity Source: UniProtKB
  • sodium ion transmembrane transport Source: UniProtKB
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-MMU-418359. Reduction of cytosolic Ca++ levels.
R-MMU-425561. Sodium/Calcium exchangers.
R-MMU-5578775. Ion homeostasis.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/calcium exchanger 2
Alternative name(s):
Na(+)/Ca(2+)-exchange protein 2
Solute carrier family 8 member 2
Gene namesi
Name:Slc8a2Imported
Synonyms:Ncx21 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:107996. Slc8a2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei69 – 8921HelicalSequence analysisAdd
BLAST
Transmembranei131 – 15121HelicalSequence analysisAdd
BLAST
Transmembranei165 – 18521HelicalSequence analysisAdd
BLAST
Transmembranei197 – 21721HelicalSequence analysisAdd
BLAST
Transmembranei226 – 24621HelicalSequence analysisAdd
BLAST
Transmembranei721 – 74121HelicalSequence analysisAdd
BLAST
Transmembranei749 – 76921HelicalSequence analysisAdd
BLAST
Transmembranei786 – 80621HelicalSequence analysisAdd
BLAST
Transmembranei823 – 84321HelicalSequence analysisAdd
BLAST
Transmembranei855 – 87521HelicalSequence analysisAdd
BLAST
Transmembranei893 – 91321HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

No obvious phenotype. In hippocampus pyramidal neurons, calcium exchange activity is reduced by about half, suggesting that other, additonal calcium exchangers are active in these neurons. In these neurons, the neurotransmitter glutamate triggers a sharp increase in cellular Ca2+ that does not depend on calcium exchanger activity. In contrast, the decrease to basal levels is mediated by calcium exchangers, and is considerably slower in mutant mice than in wild-type. Basal synaptic function is not impaired in mutant mice, but they display enhanced short-term plasticity and facilitated long-term potentiation, probably due to the slower decrease of Ca2+ after an initial impulse. Mutant mice display an increased capacity for spatial learning and memory (PubMed:12818181). Heterozygous mutants show increased basal urine volume and increased urinary secretion of Ca2+ and Na+ (PubMed:25498502).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Chaini21 – 921901Sodium/calcium exchanger 2PRO_0000434796Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi125 – 1251N-linked (GlcNAc...)Sequence analysis
Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence analysis
Modified residuei622 – 6221PhosphoserineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ8K596.
PaxDbiQ68EG0.

PTM databases

iPTMnetiQ8K596.
SwissPalmiQ8K596.

Expressioni

Tissue specificityi

Detected in kidney cortex, in distal convoluted tubules and connecting segments (PubMed:25498502). Detected in brain and spinal cord (at protein level) (PubMed:12818181). Detected in brain, especially in hippocampus CA1, CA2 and CA3 fiels, dentate gyrus, cerebellum and brain cortex (PubMed:12818181).2 Publications

Gene expression databases

BgeeiQ68EG0.

Interactioni

Protein-protein interaction databases

IntActiQ8K596. 1 interaction.
STRINGi10090.ENSMUSP00000128926.

Structurei

3D structure databases

ProteinModelPortaliQ8K596.
SMRiQ8K596. Positions 394-674.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini389 – 48294Calx-beta 1Sequence analysisAdd
BLAST
Domaini512 – 611100Calx-beta 2Sequence analysisAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni248 – 26720Putative calmodulin-binding regionBy similarityAdd
BLAST

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

eggNOGiNOG241889.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
KOiK05849.
OMAiAHSQCME.
OrthoDBiEOG7S4X56.
PhylomeDBiQ8K596.
TreeFamiTF314308.

Family and domain databases

InterProiIPR003644. Calx_beta.
IPR004836. Na_Ca_Ex.
IPR032452. Na_Ca_Ex_C-exten.
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.
SMARTiSM00237. Calx_beta. 2 hits.
[Graphical view]
TIGRFAMsiTIGR00845. caca. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8K596-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAPLALMGVV LLLGVPHCLG EATPTPSLPP PTANDSDASP EGCQGSYRCQ
60 70 80 90 100
PGVLLPVWEP EDPSLGDKVA RAVVYFVAMV YMFLGVSIIA DRFMASIEVI
110 120 130 140 150
TSKEKEITIT KANGETSVGT VRIWNETVSN LTLMALGSSA PEILLTVIEV
160 170 180 190 200
CGHNFQAGEL GPGTIVGSAA FNMFVVIAVC VYVIPAGESR KIKHLRVFFV
210 220 230 240 250
TASWSIFAYV WLYLILAVFS PGVVQVWEAL LTLIFFPVCV VFAWMADKRL
260 270 280 290 300
LFYKYVYKRY RTDPRSGIII GAEGDPPKSI ELDGTFVGTE VPGELGALGT
310 320 330 340 350
GPAEARELDA SRREVIQILK DLKQKHPDKD LEQLMGIAKY YALLHQQKSR
360 370 380 390 400
AFYRIQATRL MTGAGNVLRR HAADAARRPG ATDGAPDDED DGASRIFFEP
410 420 430 440 450
SLYHCLENCG SVLLSVACQG GEGNSTFYVD YRTEDGSAKA GSDYEYSEGT
460 470 480 490 500
LVFKPGETQK DLRIGIIDDD IFEEDEHFFV RLLNLRVGDA QGMFEPDGGG
510 520 530 540 550
RPKGRLVAPL LATVTILDDD HAGIFSFQDR LLHVSECMGT VDVRVVRSSG
560 570 580 590 600
ARGTVRLPYR TVDGTARGGG VHYEDACGEL EFGDDETMKT LQVKIVDDEE
610 620 630 640 650
YEKKDNFFIE LGQPQWLKRG ISALLLNQGN GDKKITAEQE EAQRIAEMGK
660 670 680 690 700
PVLGENNRLE VIIEESYDFK NTVDKLIKKT NLALVIGTHS WREQFIEAVT
710 720 730 740 750
VSAGDEEEDE DGPREERLPS CFDYVMHFLT VFWKVLFACV PPTEYCNGWA
760 770 780 790 800
CFGVCILVIG VLTALIGDLA SHFGCTVGLK DSVNAVVFVA LGTSIPDTFA
810 820 830 840 850
SKVAALQDQC ADASIGNVTG SNAVNVFLGL GVAWSVAAVY WAVQGRPFEV
860 870 880 890 900
RAGTLAFSVT LFTVFAFVCI AVLLYRRRPQ IGGELGGPRG PKLATTALFL
910 920
GLWFLYILFS SLEAYCHIRG F
Length:921
Mass (Da):100,711
Last modified:October 1, 2002 - v1
Checksum:i5F5A378FF982073D
GO
Isoform 2 (identifier: Q8K596-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     623-628: Missing.

Show »
Length:915
Mass (Da):100,059
Checksum:i7ECA46A5FD88D85D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti260 – 2601Y → C in BAB85834 (PubMed:12581871).Curated
Sequence conflicti387 – 3871D → G in BAB85834 (PubMed:12581871).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei623 – 6286Missing in isoform 2. VSP_057980

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF503502 mRNA. Translation: AAM22231.1.
AC151733 Genomic DNA. No translation available.
CH466654 Genomic DNA. Translation: EDL42109.1.
BC058704 mRNA. Translation: AAH58704.1.
BC080277 mRNA. Translation: AAH80277.1.
AB080745 mRNA. Translation: BAB85834.1.
CCDSiCCDS20845.1. [Q8K596-1]
RefSeqiNP_683748.1. NM_148946.2. [Q8K596-1]
XP_006539533.1. XM_006539470.2. [Q8K596-2]
UniGeneiMm.241147.

Genome annotation databases

EnsembliENSMUST00000168693; ENSMUSP00000128926; ENSMUSG00000030376. [Q8K596-1]
GeneIDi110891.
KEGGimmu:110891.
UCSCiuc009fgz.1. mouse. [Q8K596-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF503502 mRNA. Translation: AAM22231.1.
AC151733 Genomic DNA. No translation available.
CH466654 Genomic DNA. Translation: EDL42109.1.
BC058704 mRNA. Translation: AAH58704.1.
BC080277 mRNA. Translation: AAH80277.1.
AB080745 mRNA. Translation: BAB85834.1.
CCDSiCCDS20845.1. [Q8K596-1]
RefSeqiNP_683748.1. NM_148946.2. [Q8K596-1]
XP_006539533.1. XM_006539470.2. [Q8K596-2]
UniGeneiMm.241147.

3D structure databases

ProteinModelPortaliQ8K596.
SMRiQ8K596. Positions 394-674.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8K596. 1 interaction.
STRINGi10090.ENSMUSP00000128926.

PTM databases

iPTMnetiQ8K596.
SwissPalmiQ8K596.

Proteomic databases

MaxQBiQ8K596.
PaxDbiQ68EG0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000168693; ENSMUSP00000128926; ENSMUSG00000030376. [Q8K596-1]
GeneIDi110891.
KEGGimmu:110891.
UCSCiuc009fgz.1. mouse. [Q8K596-1]

Organism-specific databases

CTDi6543.
MGIiMGI:107996. Slc8a2.

Phylogenomic databases

eggNOGiNOG241889.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
KOiK05849.
OMAiAHSQCME.
OrthoDBiEOG7S4X56.
PhylomeDBiQ8K596.
TreeFamiTF314308.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiSlc8a2. mouse.
NextBioi364879.
SOURCEiSearch...

Gene expression databases

BgeeiQ68EG0.

Family and domain databases

InterProiIPR003644. Calx_beta.
IPR004836. Na_Ca_Ex.
IPR032452. Na_Ca_Ex_C-exten.
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.
SMARTiSM00237. Calx_beta. 2 hits.
[Graphical view]
TIGRFAMsiTIGR00845. caca. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Towards a complete inventory of calcium transporters of the house mouse."
    Kraev A.
    Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: CerebellumImported.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Brain.
  5. "Hypoxia up-regulates glyceraldehyde-3-phosphate dehydrogenase in mouse brain capillary endothelial cells: involvement of Na+/Ca2+ exchanger."
    Yamaji R., Fujita K., Takahashi S., Yoneda H., Nagao K., Masuda W., Naito M., Tsuruo T., Miyatake K., Inui H., Nakano Y.
    Biochim. Biophys. Acta 1593:269-276(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 230-400.
    Strain: BALB/cJImported.
    Tissue: Brain capillaryImported.
  6. "Enhanced learning and memory in mice lacking Na+/Ca2+ exchanger 2."
    Jeon D., Yang Y.M., Jeong M.J., Philipson K.D., Rhim H., Shin H.S.
    Neuron 38:965-976(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-622, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain and Testis.
  8. "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.
  9. "Genetic knockout and pharmacologic inhibition of NCX2 cause natriuresis and hypercalciuria."
    Gotoh Y., Kita S., Fujii M., Tagashira H., Horie I., Arai Y., Uchida S., Iwamoto T.
    Biochem. Biophys. Res. Commun. 456:670-675(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiNAC2_MOUSE
AccessioniPrimary (citable) accession number: Q8K596
Secondary accession number(s): Q68EG0, Q8R504
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 9, 2015
Last sequence update: October 1, 2002
Last modified: April 13, 2016
This is version 96 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.