UniProtKB - Q9UPR5 (NAC2_HUMAN)
Protein
Sodium/calcium exchanger 2
Gene
SLC8A2
Organism
Homo sapiens (Human)
Status
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
Activity regulationi
Calcium transport is down-regulated by Na+ and stimulated by Ca2+.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 407 | Calcium 1By similarity | 1 | |
Metal bindingi | 407 | Calcium 2By similarity | 1 | |
Metal bindingi | 407 | Calcium 3By similarity | 1 | |
Metal bindingi | 443 | Calcium 1By similarity | 1 | |
Metal bindingi | 443 | Calcium 4By similarity | 1 | |
Metal bindingi | 468 | Calcium 2By similarity | 1 | |
Metal bindingi | 469 | Calcium 1By similarity | 1 | |
Metal bindingi | 469 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 469 | Calcium 3By similarity | 1 | |
Metal bindingi | 469 | Calcium 4By similarity | 1 | |
Metal bindingi | 471 | Calcium 3; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 473 | Calcium 1By similarity | 1 | |
Metal bindingi | 473 | Calcium 3By similarity | 1 | |
Metal bindingi | 473 | Calcium 4By similarity | 1 | |
Metal bindingi | 476 | Calcium 4By similarity | 1 | |
Metal bindingi | 518 | Calcium 3By similarity | 1 | |
Metal bindingi | 519 | Calcium 2By similarity | 1 | |
Metal bindingi | 520 | Calcium 2By similarity | 1 | |
Metal bindingi | 520 | Calcium 3By similarity | 1 | |
Metal bindingi | 536 | Calcium 5By similarity | 1 | |
Metal bindingi | 598 | Calcium 5By similarity | 1 | |
Metal bindingi | 598 | Calcium 6By similarity | 1 | |
Metal bindingi | 599 | Calcium 6By similarity | 1 | |
Metal bindingi | 600 | Calcium 5; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 600 | Calcium 6By similarity | 1 | |
Metal bindingi | 665 | Calcium 5By similarity | 1 |
GO - Molecular functioni
- calcium:cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration Source: ARUK-UCL
- calcium:sodium antiporter activity Source: UniProtKB
- calcium ion transmembrane transporter activity Source: ARUK-UCL
- calmodulin binding Source: UniProtKB-KW
- cation:cation antiporter activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- sodium ion transmembrane transporter activity Source: ARUK-UCL
GO - Biological processi
- calcium ion export across plasma membrane Source: ARUK-UCL
- calcium ion import across plasma membrane Source: GO_Central
- calcium ion transmembrane transport Source: UniProtKB
- cell communication Source: InterPro
- cellular calcium ion homeostasis Source: UniProtKB
- cognition Source: ARUK-UCL
- ion transport Source: Reactome
- learning Source: UniProtKB
- learning or memory Source: ARUK-UCL
- long-term synaptic potentiation Source: UniProtKB
- memory Source: UniProtKB
- metal ion transport Source: GO_Central
- modulation of excitatory postsynaptic potential Source: ARUK-UCL
- neuron cellular homeostasis Source: ARUK-UCL
- positive regulation of protein serine/threonine kinase activity Source: ARUK-UCL
- regulation of action potential firing pattern Source: ARUK-UCL
- regulation of calcineurin-mediated signaling Source: ARUK-UCL
- regulation of cardiac conduction Source: Reactome
- regulation of cytosolic calcium ion concentration Source: ARUK-UCL
- regulation of gene expression Source: ARUK-UCL
- regulation of short-term neuronal synaptic plasticity Source: UniProtKB
- response to ischemia Source: ARUK-UCL
- sodium ion transmembrane transport Source: UniProtKB
- synapse organization Source: ARUK-UCL
- transport across blood-brain barrier Source: ARUK-UCL
Keywordsi
Molecular function | Calmodulin-binding |
Biological process | Antiport, Calcium transport, Ion transport, Sodium transport, Transport |
Ligand | Calcium, Metal-binding, Sodium |
Enzyme and pathway databases
PathwayCommonsi | Q9UPR5 |
Reactomei | R-HSA-418359, Reduction of cytosolic Ca++ levels R-HSA-425561, Sodium/Calcium exchangers R-HSA-5578775, Ion homeostasis |
Protein family/group databases
TCDBi | 2.A.19.3.5, the ca(2+):cation antiporter (caca) family |
Names & Taxonomyi
Protein namesi | Recommended name: Sodium/calcium exchanger 2Alternative name(s): Na(+)/Ca(2+)-exchange protein 2 Solute carrier family 8 member 2 |
Gene namesi | Name:SLC8A2 Synonyms:KIAA1087, NCX2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11069, SLC8A2 |
MIMi | 601901, gene |
neXtProti | NX_Q9UPR5 |
VEuPathDBi | HostDB:ENSG00000118160.13 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Multi-pass membrane protein By similarity
- Basolateral cell membrane By similarity; Multi-pass membrane protein By similarity
Other locations
- Perikaryon By similarity
- dendrite By similarity
- dendritic spine By similarity
Plasma Membrane
- basolateral plasma membrane Source: UniProtKB-SubCell
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: Reactome
- sarcolemma Source: GO_Central
Other locations
- axon Source: ARUK-UCL
- axon terminus Source: ARUK-UCL
- dendrite Source: ARUK-UCL
- dendritic spine Source: UniProtKB-SubCell
- membrane Source: GO_Central
- neuronal cell body Source: ARUK-UCL
- perikaryon Source: UniProtKB-SubCell
- postsynapse Source: GO_Central
- postsynaptic density Source: ARUK-UCL
- presynapse Source: ARUK-UCL
- synapse Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 21 – 68 | ExtracellularSequence analysisAdd BLAST | 48 | |
Transmembranei | 69 – 90 | HelicalSequence analysisAdd BLAST | 22 | |
Topological domaini | 91 – 130 | CytoplasmicSequence analysisAdd BLAST | 40 | |
Transmembranei | 131 – 152 | HelicalSequence analysisAdd BLAST | 22 | |
Topological domaini | 153 – 164 | ExtracellularSequence analysisAdd BLAST | 12 | |
Transmembranei | 165 – 185 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 186 – 196 | CytoplasmicSequence analysisAdd BLAST | 11 | |
Transmembranei | 197 – 219 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 220 – 222 | ExtracellularSequence analysis | 3 | |
Transmembranei | 223 – 246 | HelicalSequence analysisAdd BLAST | 24 | |
Topological domaini | 247 – 720 | CytoplasmicSequence analysisAdd BLAST | 474 | |
Transmembranei | 721 – 740 | HelicalSequence analysisAdd BLAST | 20 | |
Topological domaini | 741 – 747 | ExtracellularSequence analysis | 7 | |
Transmembranei | 748 – 770 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 771 – 772 | CytoplasmicSequence analysis | 2 | |
Transmembranei | 773 – 791 | HelicalSequence analysisAdd BLAST | 19 | |
Topological domaini | 792 – 822 | ExtracellularSequence analysisAdd BLAST | 31 | |
Transmembranei | 823 – 843 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 844 – 854 | CytoplasmicSequence analysisAdd BLAST | 11 | |
Transmembranei | 855 – 875 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 876 – 892 | ExtracellularSequence analysisAdd BLAST | 17 | |
Transmembranei | 893 – 909 | HelicalSequence analysisAdd BLAST | 17 | |
Topological domaini | 910 – 921 | CytoplasmicSequence analysisAdd BLAST | 12 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Membrane, SynapsePathology & Biotechi
Organism-specific databases
DisGeNETi | 6543 |
OpenTargetsi | ENSG00000118160 |
PharmGKBi | PA313 |
Miscellaneous databases
Pharosi | Q9UPR5, Tbio |
Genetic variation databases
BioMutai | SLC8A2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
ChainiPRO_0000019382 | 21 – 921 | Sodium/calcium exchanger 2Add BLAST | 901 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 34 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 622 | PhosphoserineBy similarity | 1 | |
Glycosylationi | 817 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
EPDi | Q9UPR5 |
jPOSTi | Q9UPR5 |
MassIVEi | Q9UPR5 |
MaxQBi | Q9UPR5 |
PaxDbi | Q9UPR5 |
PeptideAtlasi | Q9UPR5 |
PRIDEi | Q9UPR5 |
ProteomicsDBi | 85427 |
PTM databases
GlyGeni | Q9UPR5, 2 sites |
iPTMneti | Q9UPR5 |
PhosphoSitePlusi | Q9UPR5 |
Expressioni
Gene expression databases
Bgeei | ENSG00000118160, Expressed in cerebellum and 128 other tissues |
ExpressionAtlasi | Q9UPR5, baseline and differential |
Genevisiblei | Q9UPR5, HS |
Organism-specific databases
HPAi | ENSG00000118160, Tissue enriched (brain) |
Interactioni
GO - Molecular functioni
- calmodulin binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 112434, 1 interactor |
IntActi | Q9UPR5, 4 interactors |
MINTi | Q9UPR5 |
STRINGi | 9606.ENSP00000236877 |
Miscellaneous databases
RNActi | Q9UPR5, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 135 – 175 | Alpha-1Add BLAST | 41 | |
Domaini | 384 – 483 | Calx-beta 1Add BLAST | 100 | |
Domaini | 512 – 612 | Calx-beta 2Add BLAST | 101 | |
Repeati | 790 – 826 | Alpha-2Add BLAST | 37 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 248 – 267 | Putative calmodulin-binding regionBy similarityAdd BLAST | 20 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 29 – 32 | Poly-Pro | 4 | |
Compositional biasi | 638 – 641 | Poly-Glu | 4 |
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
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily. [View classification]Curated
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1306, Eukaryota |
GeneTreei | ENSGT00940000158344 |
HOGENOMi | CLU_012872_1_0_1 |
InParanoidi | Q9UPR5 |
OMAi | ELEKHAM |
OrthoDBi | 490546at2759 |
PhylomeDBi | Q9UPR5 |
TreeFami | TF314308 |
Family and domain databases
Gene3Di | 2.60.40.2030, 2 hits |
InterProi | View protein in InterPro IPR038081, CalX-like_sf IPR003644, Calx_beta IPR004836, Na_Ca_Ex IPR032452, Na_Ca_Ex_C-exten IPR004837, NaCa_Exmemb |
Pfami | View protein in Pfam PF03160, Calx-beta, 2 hits PF01699, Na_Ca_ex, 2 hits PF16494, Na_Ca_ex_C, 1 hit |
PRINTSi | PR01259, NACAEXCHNGR |
SMARTi | View protein in SMART SM00237, Calx_beta, 2 hits |
SUPFAMi | SSF141072, SSF141072, 2 hits |
TIGRFAMsi | TIGR00845, caca, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q9UPR5-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H6L7 | F5H6L7_HUMAN | Sodium/calcium exchanger 2 | SLC8A2 | 677 | Annotation score: | ||
M0R1Z4 | M0R1Z4_HUMAN | Sodium/calcium exchanger 2 | SLC8A2 | 145 | Annotation score: | ||
M0R211 | M0R211_HUMAN | Sodium/calcium exchanger 2 | SLC8A2 | 159 | Annotation score: |
Sequence cautioni
The sequence BAA83039 differs from that shown. Reason: Erroneous initiation.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072078 | 29 | P → L Found in a family with atypical autism and severe epilepsy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201723439Ensembl. | 1 | |
Natural variantiVAR_050226 | 429 | V → L. Corresponds to variant dbSNP:rs17759929Ensembl. | 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 |
CCDSi | CCDS33065.1 |
RefSeqi | NP_055878.1, NM_015063.2 |
Genome annotation databases
Ensembli | ENST00000236877; ENSP00000236877; ENSG00000118160 |
GeneIDi | 6543 |
KEGGi | hsa:6543 |
UCSCi | uc002pgx.4, human |
Similar proteinsi
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 |
CCDSi | CCDS33065.1 |
RefSeqi | NP_055878.1, NM_015063.2 |
3D structure databases
SMRi | Q9UPR5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 112434, 1 interactor |
IntActi | Q9UPR5, 4 interactors |
MINTi | Q9UPR5 |
STRINGi | 9606.ENSP00000236877 |
Protein family/group databases
TCDBi | 2.A.19.3.5, the ca(2+):cation antiporter (caca) family |
PTM databases
GlyGeni | Q9UPR5, 2 sites |
iPTMneti | Q9UPR5 |
PhosphoSitePlusi | Q9UPR5 |
Genetic variation databases
BioMutai | SLC8A2 |
Proteomic databases
EPDi | Q9UPR5 |
jPOSTi | Q9UPR5 |
MassIVEi | Q9UPR5 |
MaxQBi | Q9UPR5 |
PaxDbi | Q9UPR5 |
PeptideAtlasi | Q9UPR5 |
PRIDEi | Q9UPR5 |
ProteomicsDBi | 85427 |
Protocols and materials databases
Antibodypediai | 54559, 77 antibodies |
DNASUi | 6543 |
Genome annotation databases
Ensembli | ENST00000236877; ENSP00000236877; ENSG00000118160 |
GeneIDi | 6543 |
KEGGi | hsa:6543 |
UCSCi | uc002pgx.4, human |
Organism-specific databases
CTDi | 6543 |
DisGeNETi | 6543 |
GeneCardsi | SLC8A2 |
HGNCi | HGNC:11069, SLC8A2 |
HPAi | ENSG00000118160, Tissue enriched (brain) |
MIMi | 601901, gene |
neXtProti | NX_Q9UPR5 |
OpenTargetsi | ENSG00000118160 |
PharmGKBi | PA313 |
VEuPathDBi | HostDB:ENSG00000118160.13 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1306, Eukaryota |
GeneTreei | ENSGT00940000158344 |
HOGENOMi | CLU_012872_1_0_1 |
InParanoidi | Q9UPR5 |
OMAi | ELEKHAM |
OrthoDBi | 490546at2759 |
PhylomeDBi | Q9UPR5 |
TreeFami | TF314308 |
Enzyme and pathway databases
PathwayCommonsi | Q9UPR5 |
Reactomei | R-HSA-418359, Reduction of cytosolic Ca++ levels R-HSA-425561, Sodium/Calcium exchangers R-HSA-5578775, Ion homeostasis |
Miscellaneous databases
BioGRID-ORCSi | 6543, 4 hits in 874 CRISPR screens |
ChiTaRSi | SLC8A2, human |
GenomeRNAii | 6543 |
Pharosi | Q9UPR5, Tbio |
PROi | PR:Q9UPR5 |
RNActi | Q9UPR5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000118160, Expressed in cerebellum and 128 other tissues |
ExpressionAtlasi | Q9UPR5, baseline and differential |
Genevisiblei | Q9UPR5, HS |
Family and domain databases
Gene3Di | 2.60.40.2030, 2 hits |
InterProi | View protein in InterPro IPR038081, CalX-like_sf IPR003644, Calx_beta IPR004836, Na_Ca_Ex IPR032452, Na_Ca_Ex_C-exten IPR004837, NaCa_Exmemb |
Pfami | View protein in Pfam PF03160, Calx-beta, 2 hits PF01699, Na_Ca_ex, 2 hits PF16494, Na_Ca_ex_C, 1 hit |
PRINTSi | PR01259, NACAEXCHNGR |
SMARTi | View protein in SMART SM00237, Calx_beta, 2 hits |
SUPFAMi | SSF141072, SSF141072, 2 hits |
TIGRFAMsi | TIGR00845, caca, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NAC2_HUMAN | |
Accessioni | Q9UPR5Primary (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: | February 10, 2021 | |
This is version 159 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants