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Protein

Sodium/calcium exchanger 2

Gene

SLC8A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. Plays a role in regulating urinary Ca2+ and Na+ excretion.By similarity

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi407Calcium 1By similarity1
Metal bindingi407Calcium 2By similarity1
Metal bindingi407Calcium 3By similarity1
Metal bindingi443Calcium 1By similarity1
Metal bindingi443Calcium 4By similarity1
Metal bindingi468Calcium 2By similarity1
Metal bindingi469Calcium 1By similarity1
Metal bindingi469Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi469Calcium 3By similarity1
Metal bindingi469Calcium 4By similarity1
Metal bindingi471Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi473Calcium 1By similarity1
Metal bindingi473Calcium 3By similarity1
Metal bindingi473Calcium 4By similarity1
Metal bindingi476Calcium 4By similarity1
Metal bindingi518Calcium 3By similarity1
Metal bindingi519Calcium 2By similarity1
Metal bindingi520Calcium 2By similarity1
Metal bindingi520Calcium 3By similarity1
Metal bindingi536Calcium 5By similarity1
Metal bindingi598Calcium 5By similarity1
Metal bindingi598Calcium 6By similarity1
Metal bindingi599Calcium 6By similarity1
Metal bindingi600Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi600Calcium 6By similarity1
Metal bindingi665Calcium 5By similarity1

GO - Molecular functioni

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

BioCyciZFISH:ENSG00000118160-MONOMER.
ReactomeiR-HSA-418359. Reduction of cytosolic Ca++ levels.
R-HSA-425561. Sodium/Calcium exchangers.
R-HSA-5578775. Ion homeostasis.

Protein family/group databases

TCDBi2.A.19.3.5. the ca(2+):cation antiporter (caca) family.

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:KIAA1087, NCX2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:11069. SLC8A2.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity
  • Basolateral cell membrane By similarity; Multi-pass membrane protein By similarity
  • Perikaryon By similarity
  • Cell projectiondendrite By similarity
  • Cell projectiondendritic spine By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 68ExtracellularSequence analysisAdd BLAST48
Transmembranei69 – 90HelicalSequence analysisAdd BLAST22
Topological domaini91 – 130CytoplasmicSequence analysisAdd BLAST40
Transmembranei131 – 152HelicalSequence analysisAdd BLAST22
Topological domaini153 – 164ExtracellularSequence analysisAdd BLAST12
Transmembranei165 – 185HelicalSequence analysisAdd BLAST21
Topological domaini186 – 196CytoplasmicSequence analysisAdd BLAST11
Transmembranei197 – 219HelicalSequence analysisAdd BLAST23
Topological domaini220 – 222ExtracellularSequence analysis3
Transmembranei223 – 246HelicalSequence analysisAdd BLAST24
Topological domaini247 – 720CytoplasmicSequence analysisAdd BLAST474
Transmembranei721 – 740HelicalSequence analysisAdd BLAST20
Topological domaini741 – 747ExtracellularSequence analysis7
Transmembranei748 – 770HelicalSequence analysisAdd BLAST23
Topological domaini771 – 772CytoplasmicSequence analysis2
Transmembranei773 – 791HelicalSequence analysisAdd BLAST19
Topological domaini792 – 822ExtracellularSequence analysisAdd BLAST31
Transmembranei823 – 843HelicalSequence analysisAdd BLAST21
Topological domaini844 – 854CytoplasmicSequence analysisAdd BLAST11
Transmembranei855 – 875HelicalSequence analysisAdd BLAST21
Topological domaini876 – 892ExtracellularSequence analysisAdd BLAST17
Transmembranei893 – 909HelicalSequence analysisAdd BLAST17
Topological domaini910 – 921CytoplasmicSequence analysisAdd BLAST12

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6543.
OpenTargetsiENSG00000118160.
PharmGKBiPA313.

Polymorphism and mutation databases

BioMutaiSLC8A2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001938221 – 921Sodium/calcium exchanger 2Add BLAST901

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi34N-linked (GlcNAc...)Sequence analysis1
Modified residuei622PhosphoserineBy similarity1
Glycosylationi817N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9UPR5.
MaxQBiQ9UPR5.
PaxDbiQ9UPR5.
PeptideAtlasiQ9UPR5.
PRIDEiQ9UPR5.

PTM databases

iPTMnetiQ9UPR5.
PhosphoSitePlusiQ9UPR5.

Expressioni

Gene expression databases

BgeeiENSG00000118160.
CleanExiHS_SLC8A2.
ExpressionAtlasiQ9UPR5. baseline and differential.
GenevisibleiQ9UPR5. HS.

Organism-specific databases

HPAiHPA050818.
HPA054671.

Interactioni

Protein-protein interaction databases

BioGridi112434. 1 interactor.
STRINGi9606.ENSP00000236877.

Structurei

3D structure databases

ProteinModelPortaliQ9UPR5.
SMRiQ9UPR5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati135 – 175Alpha-1Add BLAST41
Domaini384 – 483Calx-beta 1Add BLAST100
Domaini512 – 612Calx-beta 2Add BLAST101
Repeati790 – 826Alpha-2Add BLAST37

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni248 – 267Putative calmodulin-binding regionBy similarityAdd BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi29 – 32Poly-Pro4
Compositional biasi638 – 641Poly-Glu4

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.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiQ9UPR5.
KOiK05849.
OMAiAHSQCME.
OrthoDBiEOG091G0EC1.
PhylomeDBiQ9UPR5.
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.

Sequencei

Sequence statusi: Complete.

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

Q9UPR5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPLALVGVT LLLAAPPCSG AATPTPSLPP PPANDSDTST GGCQGSYRCQ
60 70 80 90 100
PGVLLPVWEP DDPSLGDKAA RAVVYFVAMV YMFLGVSIIA DRFMAAIEVI
110 120 130 140 150
TSKEKEITIT KANGETSVGT VRIWNETVSN LTLMALGSSA PEILLSVIEV
160 170 180 190 200
CGHNFQAGEL GPGTIVGSAA FNMFVVIAVC IYVIPAGESR KIKHLRVFFV
210 220 230 240 250
TASWSIFAYV WLYLILAVFS PGVVQVWEAL LTLVFFPVCV VFAWMADKRL
260 270 280 290 300
LFYKYVYKRY RTDPRSGIII GAEGDPPKSI ELDGTFVGAE APGELGGLGP
310 320 330 340 350
GPAEARELDA SRREVIQILK DLKQKHPDKD LEQLVGIANY YALLHQQKSR
360 370 380 390 400
AFYRIQATRL MTGAGNVLRR HAADASRRAA PAEGAGEDED DGASRIFFEP
410 420 430 440 450
SLYHCLENCG SVLLSVTCQG 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 EARRIAEMGK
660 670 680 690 700
PVLGENCRLE VIIEESYDFK NTVDKLIKKT NLALVIGTHS WREQFLEAIT
710 720 730 740 750
VSAGDEEEEE DGSREERLPS CFDYVMHFLT VFWKVLFACV PPTEYCHGWA
760 770 780 790 800
CFGVSILVIG 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
GLWLLYILFA SLEAYCHIRG F
Length:921
Mass (Da):100,368
Last modified:December 1, 2000 - v2
Checksum:i798CDF7E32B9410C
GO

Sequence cautioni

The sequence BAA83039 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07207829P → L Found in a family with atypical autism and severe epilepsy; unknown pathological significance. 1 PublicationCorresponds to variant rs201723439dbSNPEnsembl.1
Natural variantiVAR_050226429V → L.Corresponds to variant rs17759929dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB029010 mRNA. Translation: BAA83039.1. Different initiation.
AK302552 mRNA. Translation: BAG63821.1.
CH471126 Genomic DNA. Translation: EAW57485.1.
CCDSiCCDS33065.1.
RefSeqiNP_055878.1. NM_015063.2.
UniGeneiHs.172884.

Genome annotation databases

EnsembliENST00000236877; ENSP00000236877; ENSG00000118160.
GeneIDi6543.
KEGGihsa:6543.
UCSCiuc002pgx.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB029010 mRNA. Translation: BAA83039.1. Different initiation.
AK302552 mRNA. Translation: BAG63821.1.
CH471126 Genomic DNA. Translation: EAW57485.1.
CCDSiCCDS33065.1.
RefSeqiNP_055878.1. NM_015063.2.
UniGeneiHs.172884.

3D structure databases

ProteinModelPortaliQ9UPR5.
SMRiQ9UPR5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112434. 1 interactor.
STRINGi9606.ENSP00000236877.

Protein family/group databases

TCDBi2.A.19.3.5. the ca(2+):cation antiporter (caca) family.

PTM databases

iPTMnetiQ9UPR5.
PhosphoSitePlusiQ9UPR5.

Polymorphism and mutation databases

BioMutaiSLC8A2.

Proteomic databases

EPDiQ9UPR5.
MaxQBiQ9UPR5.
PaxDbiQ9UPR5.
PeptideAtlasiQ9UPR5.
PRIDEiQ9UPR5.

Protocols and materials databases

DNASUi6543.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000236877; ENSP00000236877; ENSG00000118160.
GeneIDi6543.
KEGGihsa:6543.
UCSCiuc002pgx.4. human.

Organism-specific databases

CTDi6543.
DisGeNETi6543.
GeneCardsiSLC8A2.
HGNCiHGNC:11069. SLC8A2.
HPAiHPA050818.
HPA054671.
MIMi601901. gene.
neXtProtiNX_Q9UPR5.
OpenTargetsiENSG00000118160.
PharmGKBiPA313.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiQ9UPR5.
KOiK05849.
OMAiAHSQCME.
OrthoDBiEOG091G0EC1.
PhylomeDBiQ9UPR5.
TreeFamiTF314308.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118160-MONOMER.
ReactomeiR-HSA-418359. Reduction of cytosolic Ca++ levels.
R-HSA-425561. Sodium/Calcium exchangers.
R-HSA-5578775. Ion homeostasis.

Miscellaneous databases

ChiTaRSiSLC8A2. human.
GenomeRNAii6543.
PROiQ9UPR5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118160.
CleanExiHS_SLC8A2.
ExpressionAtlasiQ9UPR5. baseline and differential.
GenevisibleiQ9UPR5. HS.

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...

Entry informationi

Entry nameiNAC2_HUMAN
AccessioniPrimary (citable) accession number: Q9UPR5
Secondary accession number(s): B4DYQ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: November 2, 2016
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.