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Protein

Sodium/calcium exchanger 2

Gene

Slc8a2

Organism
Rattus norvegicus (Rat)
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 (PubMed:8021246, PubMed:9486131). 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. Plays a role in regulating urinary Ca2+ and Na+ excretion.By similarity2 Publications

Enzyme regulationi

Calcium transport is down-regulated by Na+ and stimulated by Ca2+.2 Publications

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: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • calcium ion export from cell Source: RGD
  • calcium ion import into cell Source: RGD
  • calcium ion transport into cytosol Source: RGD
  • cell communication Source: InterPro
  • learning Source: UniProtKB
  • long-term synaptic potentiation Source: UniProtKB
  • memory Source: UniProtKB
  • regulation of short-term neuronal synaptic plasticity Source: UniProtKB
  • response to vitamin D Source: RGD
  • sodium ion transmembrane transport Source: GOC
  • sodium ion transport Source: RGD
  • telencephalon development Source: RGD
Complete GO annotation...

Keywords - Biological processi

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

Keywords - Ligandi

Calcium, Calmodulin-binding, Metal-binding, Sodium

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:Slc8a2
Synonyms:Ncx2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620194. Slc8a2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 6848ExtracellularSequence analysisAdd
BLAST
Transmembranei69 – 9022HelicalSequence analysisAdd
BLAST
Topological domaini91 – 13040CytoplasmicSequence analysisAdd
BLAST
Transmembranei131 – 15222HelicalSequence analysisAdd
BLAST
Topological domaini153 – 16412ExtracellularSequence analysisAdd
BLAST
Transmembranei165 – 18521HelicalSequence analysisAdd
BLAST
Topological domaini186 – 19611CytoplasmicSequence analysisAdd
BLAST
Transmembranei197 – 21923HelicalSequence analysisAdd
BLAST
Topological domaini220 – 2223ExtracellularSequence analysis
Transmembranei223 – 24624HelicalSequence analysisAdd
BLAST
Topological domaini247 – 720474CytoplasmicSequence analysisAdd
BLAST
Transmembranei721 – 74020HelicalSequence analysisAdd
BLAST
Topological domaini741 – 7477ExtracellularSequence analysis
Transmembranei748 – 77023HelicalSequence analysisAdd
BLAST
Topological domaini771 – 7722CytoplasmicSequence analysis
Transmembranei773 – 79119HelicalSequence analysisAdd
BLAST
Topological domaini792 – 82231ExtracellularSequence analysisAdd
BLAST
Transmembranei823 – 84321HelicalSequence analysisAdd
BLAST
Topological domaini844 – 85411CytoplasmicSequence analysisAdd
BLAST
Transmembranei855 – 87521HelicalSequence analysisAdd
BLAST
Topological domaini876 – 89217ExtracellularSequence analysisAdd
BLAST
Transmembranei893 – 90917HelicalSequence analysisAdd
BLAST
Topological domaini910 – 92112CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB-SubCell
  • cell projection Source: RGD
  • dendritic spine Source: RGD
  • integral component of plasma membrane Source: UniProtKB
  • microtubule Source: RGD
  • mitochondrion Source: RGD
  • neuronal cell body Source: RGD
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Chaini21 – 921901Sodium/calcium exchanger 2PRO_0000019383Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi34 – 341N-linked (GlcNAc...)Sequence analysis
Modified residuei622 – 6221PhosphoserineBy similarity
Glycosylationi817 – 8171N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP48768.
PRIDEiP48768.

PTM databases

SwissPalmiP48768.

Expressioni

Tissue specificityi

Detected in neocortex and hippocampus on pyramidal cells, astrocyte processes and dendrites (at protein level) (PubMed:16914199). Brain and skeletal muscle.2 Publications

Interactioni

Protein-protein interaction databases

BioGridi250785. 1 interaction.
IntActiP48768. 1 interaction.
MINTiMINT-8290508.
STRINGi10116.ENSRNOP00000042012.

Structurei

3D structure databases

ProteinModelPortaliP48768.
SMRiP48768. Positions 521-674.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati135 – 17541Alpha-1Add
BLAST
Domaini384 – 483100Calx-beta 1Add
BLAST
Domaini512 – 612101Calx-beta 2Add
BLAST
Repeati790 – 82637Alpha-2Add
BLAST

Region

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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi29 – 324Poly-Pro
Compositional biasi638 – 6414Poly-Glu

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

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiP48768.
KOiK05849.

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.

Sequencei

Sequence statusi: Complete.

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

P48768-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPLALVGVA LLLGAPHCLG EATPTPSLPP PPANDSDASP GGCQGSYRCQ
60 70 80 90 100
PGVLLPVWEP DDPSLGDKAA RAVVYFVAMV YMFLGLSIIA DRFMASIEVI
110 120 130 140 150
TSKEKEITIT KANGETSVGT VRIWNETVSN LTLMALGSSA PEILLSVIEV
160 170 180 190 200
CGHNFQAGEL GPGTIVGSAA FNMFVVIAVC VYVIPAGESR KIKHLRVFFV
210 220 230 240 250
TASWSIFAYV WLYLILAVFS PGVVQVWEAL LTLVFFPVCV VFAWMADKRL
260 270 280 290 300
LFYKYVYKRY RTDPRSGIII GAEGDPPKSI ELDGTFVGTE VPGELGALGT
310 320 330 340 350
GPAEARELDA SRREVIQILK DLKQKHPDKD LEQLVGIAKY YALLHQQKSR
360 370 380 390 400
AFYRIQATRL MTGAGNVLRR HAADAARRPG ANDGAPDDED DGASRIFFEP
410 420 430 440 450
SLYHCLENCG SVLLSVACQG GEGNSTFYVD YRTEDGSAKA GSDYEYSEGT
460 470 480 490 500
LVFKPGETQK ELRIGIIDDD 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 ISALLLNQGD GDRKLTAEEE EAQRIAEMGK
660 670 680 690 700
PVLGENCRLE VIIEESYDFK NTVDKLIKKT NLALVIGTHS WREQFLEAVT
710 720 730 740 750
VSAGDEEEDE DGSREERLPS CFDYVMHFLT VFWKVLFACL PPTEYCHGWA
760 770 780 790 800
CFGVCILVIG LLTALIGDLA SHFGCTVGLK DSVNAVVFVA LGTSIPDTFA
810 820 830 840 850
SKVAALQDQC ADASIGNVTG SNAVNVFLGL GVAWSVAAVY WAVQGRPFEV
860 870 880 890 900
RTGTLAFSVT LFTVFAFVGI AVLLYRRRPH IGGELGGPRG PKLATTALFL
910 920
GLWFLYILFA SLEAYCHIRG F
Length:921
Mass (Da):100,523
Last modified:February 1, 1996 - v1
Checksum:i0CDB26BEACBCF6B1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08141 mRNA. Translation: AAA19920.1.
PIRiA54139.
RefSeqiNP_511174.1. NM_078619.1.
UniGeneiRn.10305.

Genome annotation databases

GeneIDi140447.
KEGGirno:140447.
UCSCiRGD:620194. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08141 mRNA. Translation: AAA19920.1.
PIRiA54139.
RefSeqiNP_511174.1. NM_078619.1.
UniGeneiRn.10305.

3D structure databases

ProteinModelPortaliP48768.
SMRiP48768. Positions 521-674.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250785. 1 interaction.
IntActiP48768. 1 interaction.
MINTiMINT-8290508.
STRINGi10116.ENSRNOP00000042012.

PTM databases

SwissPalmiP48768.

Proteomic databases

PaxDbiP48768.
PRIDEiP48768.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi140447.
KEGGirno:140447.
UCSCiRGD:620194. rat.

Organism-specific databases

CTDi6543.
RGDi620194. Slc8a2.

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiP48768.
KOiK05849.

Miscellaneous databases

NextBioi620477.
PROiP48768.

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

  1. "Cloning of the NCX2 isoform of the plasma membrane Na(+)-Ca2+ exchanger."
    Li Z., Matsuoka S., Hryshko L.V., Nicoll D.A., Bershon M.M., Burke E.P., Lifton R.P., Philipson K.D.
    J. Biol. Chem. 269:17434-17439(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Brain stem.
  2. Cited for: TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
  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. "Cellular and subcellular localization of Na+-Ca2+ exchanger protein isoforms, NCX1, NCX2, and NCX3 in cerebral cortex and hippocampus of adult rat."
    Minelli A., Castaldo P., Gobbi P., Salucci S., Magi S., Amoroso S.
    Cell Calcium 41:221-234(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  5. "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.

Entry informationi

Entry nameiNAC2_RAT
AccessioniPrimary (citable) accession number: P48768
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: February 17, 2016
This is version 109 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. 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.