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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)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

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-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)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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA313.

Polymorphism and mutation databases

BioMutaiSLC8A2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Chaini21 – 921901Sodium/calcium exchanger 2PRO_0000019382Add
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

EPDiQ9UPR5.
MaxQBiQ9UPR5.
PaxDbiQ9UPR5.
PeptideAtlasiQ9UPR5.
PRIDEiQ9UPR5.

PTM databases

iPTMnetiQ9UPR5.
PhosphoSiteiQ9UPR5.

Expressioni

Gene expression databases

BgeeiQ9UPR5.
CleanExiHS_SLC8A2.
ExpressionAtlasiQ9UPR5. baseline and differential.
GenevisibleiQ9UPR5. HS.

Organism-specific databases

HPAiHPA050818.
HPA054671.

Interactioni

Protein-protein interaction databases

BioGridi112434. 1 interaction.
STRINGi9606.ENSP00000236877.

Structurei

3D structure databases

ProteinModelPortaliQ9UPR5.
SMRiQ9UPR5. Positions 394-674.
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.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiQ9UPR5.
KOiK05849.
OMAiAHSQCME.
OrthoDBiEOG7S4X56.
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 BAA83039.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti29 – 291P → L Found in a family with atypical autism and severe epilepsy; unknown pathological significance. 1 Publication
Corresponds to variant rs201723439 [ dbSNP | Ensembl ].
VAR_072078
Natural varianti429 – 4291V → L.
Corresponds to variant rs17759929 [ dbSNP | Ensembl ].
VAR_050226

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. Positions 394-674.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112434. 1 interaction.
STRINGi9606.ENSP00000236877.

Protein family/group databases

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

PTM databases

iPTMnetiQ9UPR5.
PhosphoSiteiQ9UPR5.

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

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiQ9UPR5.
KOiK05849.
OMAiAHSQCME.
OrthoDBiEOG7S4X56.
PhylomeDBiQ9UPR5.
TreeFamiTF314308.

Enzyme and pathway databases

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

BgeeiQ9UPR5.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
    Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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. "Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation."
    Lee H., Lin M.C., Kornblum H.I., Papazian D.M., Nelson S.F.
    Hum. Mol. Genet. 23:3481-3489(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LEU-29.

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: July 6, 2016
This is version 133 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.