UniProtKB - P57103 (NAC3_HUMAN)
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Protein
Sodium/calcium exchanger 3
Gene
SLC8A3
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, both in muscle and in brain. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca2+ levels due to release of Ca2+ stores from the endoplasmic reticulum. SLC8A3 mediates the export of Ca2+ from the cell during the next phase, so that cytoplasmic Ca2+ levels rapidly return to baseline. Contributes to Ca2+ transport during excitation-contraction coupling in muscle. In neurons, 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 (By similarity). Required for normal oligodendrocyte differentiation and for normal myelination (PubMed:21959935). Mediates Ca2+ efflux from mitochondria and contributes to mitochondrial Ca2+ ion homeostasis (By similarity).By similarity1 Publication
Caution
Enzyme 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 | 409 | Calcium 1By similarity | 1 | |
Metal bindingi | 409 | Calcium 2By similarity | 1 | |
Metal bindingi | 409 | Calcium 3By similarity | 1 | |
Metal bindingi | 445 | Calcium 1By similarity | 1 | |
Metal bindingi | 445 | Calcium 4By similarity | 1 | |
Metal bindingi | 470 | Calcium 2By similarity | 1 | |
Metal bindingi | 471 | Calcium 1By similarity | 1 | |
Metal bindingi | 471 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 471 | Calcium 3By similarity | 1 | |
Metal bindingi | 471 | Calcium 4By similarity | 1 | |
Metal bindingi | 473 | Calcium 3; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 475 | Calcium 1By similarity | 1 | |
Metal bindingi | 475 | Calcium 3By similarity | 1 | |
Metal bindingi | 475 | Calcium 4By similarity | 1 | |
Metal bindingi | 478 | Calcium 4By similarity | 1 | |
Metal bindingi | 525 | Calcium 3By similarity | 1 | |
Metal bindingi | 526 | Calcium 2By similarity | 1 | |
Metal bindingi | 527 | Calcium 2By similarity | 1 | |
Metal bindingi | 527 | Calcium 3By similarity | 1 | |
Metal bindingi | 543 | Calcium 5By similarity | 1 | |
Metal bindingi | 579 | Calcium 6By similarity | 1 | |
Metal bindingi | 606 | Calcium 6By similarity | 1 | |
Metal bindingi | 607 | Calcium 5; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 607 | Calcium 6By similarity | 1 | |
Metal bindingi | 672 | Calcium 5By similarity | 1 |
GO - Molecular functioni
- calcium:sodium antiporter activity Source: UniProtKB
- calmodulin binding Source: UniProtKB-KW
- ion antiporter activity involved in regulation of postsynaptic membrane potential Source: Ensembl
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- calcium ion export across plasma membrane Source: Ensembl
- calcium ion import across plasma membrane Source: Ensembl
- calcium ion transmembrane transport Source: UniProtKB
- cell communication Source: InterPro
- cellular calcium ion homeostasis Source: UniProtKB
- cellular response to cAMP Source: Ensembl
- cellular response to hypoxia Source: UniProtKB
- hematopoietic progenitor cell differentiation Source: Ensembl
- ion transport Source: Reactome
- learning Source: UniProtKB
- long-term synaptic potentiation Source: UniProtKB
- memory Source: UniProtKB
- mitochondrial calcium ion homeostasis Source: UniProtKB
- mitochondrial calcium ion transmembrane transport Source: UniProtKB
- myelination Source: UniProtKB
- oligodendrocyte differentiation Source: UniProtKB
- regulation of cardiac conduction Source: Reactome
- regulation of skeletal muscle contraction Source: UniProtKB
- sodium ion transmembrane transport Source: UniProtKB
- telencephalon development Source: Ensembl
Keywordsi
Molecular function | Calmodulin-binding |
Biological process | Antiport, Calcium transport, Ion transport, Sodium transport, Transport |
Ligand | Calcium, Metal-binding, Sodium |
Enzyme and pathway databases
Reactomei | R-HSA-418359 Reduction of cytosolic Ca++ levels R-HSA-425561 Sodium/Calcium exchangers R-HSA-5578775 Ion homeostasis R-HSA-8949215 Mitochondrial calcium ion transport |
Protein family/group databases
TCDBi | 2.A.19.3.3 the ca(2+):cation antiporter (caca) family |
Names & Taxonomyi
Protein namesi | Recommended name: Sodium/calcium exchanger 3Alternative name(s): Na(+)/Ca(2+)-exchange protein 3 Solute carrier family 8 member 3 |
Gene namesi | Name:SLC8A3 Synonyms:NCX3 |
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
EuPathDBi | HostDB:ENSG00000100678.18 |
HGNCi | HGNC:11070 SLC8A3 |
MIMi | 607991 gene |
neXtProti | NX_P57103 |
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 31 – 73 | ExtracellularSequence analysisAdd BLAST | 43 | |
Transmembranei | 74 – 94 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 95 – 147 | CytoplasmicSequence analysisAdd BLAST | 53 | |
Transmembranei | 148 – 168 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 169 | ExtracellularSequence analysis | 1 | |
Transmembranei | 170 – 190 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 191 – 202 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Transmembranei | 203 – 223 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 224 – 230 | ExtracellularSequence analysis | 7 | |
Transmembranei | 231 – 251 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 252 – 726 | CytoplasmicSequence analysisAdd BLAST | 475 | |
Transmembranei | 727 – 747 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 748 – 754 | ExtracellularSequence analysis | 7 | |
Transmembranei | 755 – 775 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 776 – 778 | CytoplasmicSequence analysis | 3 | |
Transmembranei | 779 – 799 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 800 – 828 | ExtracellularSequence analysisAdd BLAST | 29 | |
Transmembranei | 829 – 849 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 850 – 860 | CytoplasmicSequence analysisAdd BLAST | 11 | |
Transmembranei | 861 – 881 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 882 – 903 | ExtracellularSequence analysisAdd BLAST | 22 | |
Transmembranei | 904 – 924 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 925 – 927 | CytoplasmicSequence analysis | 3 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membranePathology & Biotechi
Organism-specific databases
DisGeNETi | 6547 |
OpenTargetsi | ENSG00000100678 |
PharmGKBi | PA315 |
Chemistry databases
GuidetoPHARMACOLOGYi | 947 |
Polymorphism and mutation databases
DMDMi | 34395973 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 30 | Sequence analysisAdd BLAST | 30 | |
ChainiPRO_0000019384 | 31 – 927 | Sodium/calcium exchanger 3Add BLAST | 897 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 45 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 823 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
PaxDbi | P57103 |
PeptideAtlasi | P57103 |
PRIDEi | P57103 |
TopDownProteomicsi | P57103-2 [P57103-2] |
PTM databases
iPTMneti | P57103 |
PhosphoSitePlusi | P57103 |
Expressioni
Tissue specificityi
Isoform 2 is expressed in brain and skeletal muscle. Isoform 3 is expressed in excitable cells of brain, retina and skeletal muscle. Isoform 4 is expressed in skeletal muscle.1 Publication
Developmental stagei
Up-regulated during in vitro differentiation of oligodendrocytes (at protein level). Up-regulated during in vitro differentiation of oligodendrocytes.1 Publication
Gene expression databases
Bgeei | ENSG00000100678 |
CleanExi | HS_SLC8A3 |
ExpressionAtlasi | P57103 baseline and differential |
Genevisiblei | P57103 HS |
Interactioni
Subunit structurei
Interacts with AKAP1.By similarity
GO - Molecular functioni
- calmodulin binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGridi | 1124378 interactors. |
STRINGi | 9606.ENSP00000370669 |
Structurei
3D structure databases
ProteinModelPortali | P57103 |
SMRi | P57103 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 140 – 180 | Alpha-1Add BLAST | 41 | |
Domaini | 386 – 485 | Calx-beta 1Add BLAST | 100 | |
Domaini | 519 – 619 | Calx-beta 2Add BLAST | 101 | |
Repeati | 796 – 832 | Alpha-2Add BLAST | 37 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 253 – 272 | Putative calmodulin-binding regionBy similarityAdd BLAST | 20 |
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 ENOG410XPJP LUCA |
GeneTreei | ENSGT00730000110414 |
HOGENOMi | HOG000266971 |
HOVERGENi | HBG006441 |
InParanoidi | P57103 |
KOi | K05849 |
OMAi | PIWYPEN |
OrthoDBi | EOG091G0EC1 |
PhylomeDBi | P57103 |
TreeFami | TF314308 |
Family and domain databases
Gene3Di | 2.60.40.20302 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 |
s (7)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 7 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 3 (identifier: P57103-1) [UniParc]FASTAAdd to basket
Also known as: NCX3.3
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.
10 20 30 40 50
MAWLRLQPLT SAFLHFGLVT FVLFLNGLRA EAGGSGDVPS TGQNNESCSG
60 70 80 90 100
SSDCKEGVIL PIWYPENPSL GDKIARVIVY FVALIYMFLG VSIIADRFMA
110 120 130 140 150
SIEVITSQER EVTIKKPNGE TSTTTIRVWN ETVSNLTLMA LGSSAPEILL
160 170 180 190 200
SLIEVCGHGF IAGDLGPSTI VGSAAFNMFI IIGICVYVIP DGETRKIKHL
210 220 230 240 250
RVFFITAAWS IFAYIWLYMI LAVFSPGVVQ VWEGLLTLFF FPVCVLLAWV
260 270 280 290 300
ADKRLLFYKY MHKKYRTDKH RGIIIETEGD HPKGIEMDGK MMNSHFLDGN
310 320 330 340 350
LVPLEGKEVD ESRREMIRIL KDLKQKHPEK DLDQLVEMAN YYALSHQQKS
360 370 380 390 400
RAFYRIQATR MMTGAGNILK KHAAEQAKKA SSMSEVHTDE PEDFISKVFF
410 420 430 440 450
DPCSYQCLEN CGAVLLTVVR KGGDMSKTMY VDYKTEDGSA NAGADYEFTE
460 470 480 490 500
GTVVLKPGET QKEFSVGIID DDIFEEDEHF FVRLSNVRIE EEQPEEGMPP
510 520 530 540 550
AIFNSLPLPR AVLASPCVAT VTILDDDHAG IFTFECDTIH VSESIGVMEV
560 570 580 590 600
KVLRTSGARG TVIVPFRTVE GTAKGGGEDF EDTYGELEFK NDETVKTIRV
610 620 630 640 650
KIVDEEEYER QENFFIALGE PKWMERGISA LLLSPDVTDR KLTMEEEEAK
660 670 680 690 700
RIAEMGKPVL GEHPKLEVII EESYEFKTTV DKLIKKTNLA LVVGTHSWRD
710 720 730 740 750
QFMEAITVSA AGDEDEDESG EERLPSCFDY VMHFLTVFWK VLFACVPPTE
760 770 780 790 800
YCHGWACFAV SILIIGMLTA IIGDLASHFG CTIGLKDSVT AVVFVAFGTS
810 820 830 840 850
VPDTFASKAA ALQDVYADAS IGNVTGSNAV NVFLGIGLAW SVAAIYWALQ
860 870 880 890 900
GQEFHVSAGT LAFSVTLFTI FAFVCISVLL YRRRPHLGGE LGGPRGCKLA
910 920
TTWLFVSLWL LYILFATLEA YCYIKGF
Isoform 4 (identifier: P57103-3) [UniParc]FASTAAdd to basket
Also known as: NCX3.4
The sequence of this isoform differs from the canonical sequence as follows:
596-620: KTIRVKIVDEEEYERQENFFIALGE → CDRQEADYGRRGGQEDSRDGKASIG
621-927: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_036463 | 612 | E → Q in a breast cancer sample; somatic mutation. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043125 | 1 – 643 | Missing in isoform 5. 1 PublicationAdd BLAST | 643 | |
Alternative sequenceiVSP_043126 | 1 – 623 | Missing in isoform 6. 2 PublicationsAdd BLAST | 623 | |
Alternative sequenceiVSP_008117 | 596 – 620 | KTIRV…IALGE → CDRQEADYGRRGGQEDSRDG KASIG in isoform 4. 1 PublicationAdd BLAST | 25 | |
Alternative sequenceiVSP_044502 | 599 – 638 | RVKIV…SPDVT → HIKVIDDEAYEKNKNYFIEM MGPRMVDMSFQKALLLSP in isoform 8. 1 PublicationAdd BLAST | 40 | |
Alternative sequenceiVSP_008118 | 621 – 927 | Missing in isoform 4. 1 PublicationAdd BLAST | 307 | |
Alternative sequenceiVSP_008116 | 630 – 635 | Missing in isoform 2 and isoform 6. 3 Publications | 6 | |
Alternative sequenceiVSP_043850 | 636 – 638 | Missing in isoform 7. 1 Publication | 3 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | NAC3_HUMAN | |
Accessioni | P57103Primary (citable) accession number: P57103 Secondary accession number(s): Q5K3P6 Q96QG2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | August 29, 2003 | |
Last modified: | March 28, 2018 | |
This is version 145 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. |