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UniProtKB - P57103 (NAC3_HUMAN)

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Protein

Sodium/calcium exchanger 3

Gene

SLC8A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. 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 keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi409Calcium 1By similarity1
Metal bindingi409Calcium 2By similarity1
Metal bindingi409Calcium 3By similarity1
Metal bindingi445Calcium 1By similarity1
Metal bindingi445Calcium 4By similarity1
Metal bindingi470Calcium 2By similarity1
Metal bindingi471Calcium 1By similarity1
Metal bindingi471Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi471Calcium 3By similarity1
Metal bindingi471Calcium 4By similarity1
Metal bindingi473Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi475Calcium 1By similarity1
Metal bindingi475Calcium 3By similarity1
Metal bindingi475Calcium 4By similarity1
Metal bindingi478Calcium 4By similarity1
Metal bindingi525Calcium 3By similarity1
Metal bindingi526Calcium 2By similarity1
Metal bindingi527Calcium 2By similarity1
Metal bindingi527Calcium 3By similarity1
Metal bindingi543Calcium 5By similarity1
Metal bindingi579Calcium 6By similarity1
Metal bindingi606Calcium 6By similarity1
Metal bindingi607Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi607Calcium 6By similarity1
Metal bindingi672Calcium 5By similarity1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionCalmodulin-binding
Biological processAntiport, Calcium transport, Ion transport, Sodium transport, Transport
LigandCalcium, 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
R-HSA-8949215 Mitochondrial calcium ion transport

Protein family/group databases

TCDBi2.A.19.3.3 the ca(2+):cation antiporter (caca) family

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/calcium exchanger 3
Alternative name(s):
Na(+)/Ca(2+)-exchange protein 3
Solute carrier family 8 member 3
Gene namesi
Name:SLC8A3
Synonyms:NCX3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100678.18
HGNCiHGNC:11070 SLC8A3
MIMi607991 gene
neXtProtiNX_P57103

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 73ExtracellularSequence analysisAdd BLAST43
Transmembranei74 – 94HelicalSequence analysisAdd BLAST21
Topological domaini95 – 147CytoplasmicSequence analysisAdd BLAST53
Transmembranei148 – 168HelicalSequence analysisAdd BLAST21
Topological domaini169ExtracellularSequence analysis1
Transmembranei170 – 190HelicalSequence analysisAdd BLAST21
Topological domaini191 – 202CytoplasmicSequence analysisAdd BLAST12
Transmembranei203 – 223HelicalSequence analysisAdd BLAST21
Topological domaini224 – 230ExtracellularSequence analysis7
Transmembranei231 – 251HelicalSequence analysisAdd BLAST21
Topological domaini252 – 726CytoplasmicSequence analysisAdd BLAST475
Transmembranei727 – 747HelicalSequence analysisAdd BLAST21
Topological domaini748 – 754ExtracellularSequence analysis7
Transmembranei755 – 775HelicalSequence analysisAdd BLAST21
Topological domaini776 – 778CytoplasmicSequence analysis3
Transmembranei779 – 799HelicalSequence analysisAdd BLAST21
Topological domaini800 – 828ExtracellularSequence analysisAdd BLAST29
Transmembranei829 – 849HelicalSequence analysisAdd BLAST21
Topological domaini850 – 860CytoplasmicSequence analysisAdd BLAST11
Transmembranei861 – 881HelicalSequence analysisAdd BLAST21
Topological domaini882 – 903ExtracellularSequence analysisAdd BLAST22
Transmembranei904 – 924HelicalSequence analysisAdd BLAST21
Topological domaini925 – 927CytoplasmicSequence analysis3

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6547
OpenTargetsiENSG00000100678
PharmGKBiPA315

Chemistry databases

GuidetoPHARMACOLOGYi947

Polymorphism and mutation databases

DMDMi34395973

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000001938431 – 927Sodium/calcium exchanger 3Add BLAST897

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi45N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi823N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP57103
PeptideAtlasiP57103
PRIDEiP57103
TopDownProteomicsiP57103-2 [P57103-2]

PTM databases

iPTMnetiP57103
PhosphoSitePlusiP57103

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

BgeeiENSG00000100678
CleanExiHS_SLC8A3
ExpressionAtlasiP57103 baseline and differential
GenevisibleiP57103 HS

Interactioni

Subunit structurei

Interacts with AKAP1.By similarity

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi1124378 interactors.
STRINGi9606.ENSP00000370669

Structurei

3D structure databases

ProteinModelPortaliP57103
SMRiP57103
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati140 – 180Alpha-1Add BLAST41
Domaini386 – 485Calx-beta 1Add BLAST100
Domaini519 – 619Calx-beta 2Add BLAST101
Repeati796 – 832Alpha-2Add BLAST37

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni253 – 272Putative calmodulin-binding regionBy similarityAdd BLAST20

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 helix

Phylogenomic databases

eggNOGiKOG1306 Eukaryota
ENOG410XPJP LUCA
GeneTreeiENSGT00730000110414
HOGENOMiHOG000266971
HOVERGENiHBG006441
InParanoidiP57103
KOiK05849
OMAiPIWYPEN
OrthoDBiEOG091G0EC1
PhylomeDBiP57103
TreeFamiTF314308

Family and domain databases

Gene3Di2.60.40.20302 hits
InterProiView protein in InterPro
IPR038081 CalX-like_sf
IPR003644 Calx_beta
IPR004836 Na_Ca_Ex
IPR032452 Na_Ca_Ex_C-exten
IPR004837 NaCa_Exmemb
PfamiView protein in Pfam
PF03160 Calx-beta, 2 hits
PF01699 Na_Ca_ex, 2 hits
PF16494 Na_Ca_ex_C, 1 hit
PRINTSiPR01259 NACAEXCHNGR
SMARTiView protein in SMART
SM00237 Calx_beta, 2 hits
SUPFAMiSSF141072 SSF141072, 2 hits
TIGRFAMsiTIGR00845 caca, 1 hit

Sequences (7)i

Sequence statusi: Complete.

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

This entry describes 7 isoformsi produced by alternative 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.

« Hide

        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
Length:927
Mass (Da):103,010
Last modified:August 29, 2003 - v2
Checksum:i7B43CB6A9D77615E
GO
Isoform 2 (identifier: P57103-2) [UniParc]FASTAAdd to basket
Also known as: NCX3.2

The sequence of this isoform differs from the canonical sequence as follows:
     630-635: Missing.

Show »
Length:921
Mass (Da):102,415
Checksum:i9E7E932E8EAE13F7
GO
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 »
Length:620
Mass (Da):68,947
Checksum:i0FBEC381D196FD7C
GO
Isoform 5 (identifier: P57103-4) [UniParc]FASTAAdd to basket
Also known as: NCX3-tN.1

The sequence of this isoform differs from the canonical sequence as follows:
     1-643: Missing.

Note: Expressed in fetal brain.
Show »
Length:284
Mass (Da):31,142
Checksum:i14B4A98B3DE17144
GO
Isoform 6 (identifier: P57103-5) [UniParc]FASTAAdd to basket
Also known as: NCX3-tN.2

The sequence of this isoform differs from the canonical sequence as follows:
     1-623: Missing.
     630-635: Missing.

Note: Expressed in fetal brain.
Show »
Length:298
Mass (Da):32,745
Checksum:i6B91455189B786D7
GO
Isoform 7 (identifier: P57103-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     636-638: Missing.

Show »
Length:924
Mass (Da):102,694
Checksum:iA0A556B753998A07
GO
Isoform 8 (identifier: P57103-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     599-638: RVKIVDEEEY...SALLLSPDVT → HIKVIDDEAY...SFQKALLLSP

Show »
Length:925
Mass (Da):102,804
Checksum:i0CCF8DA0881C4FDA
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036463612E → Q in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0431251 – 643Missing in isoform 5. 1 PublicationAdd BLAST643
Alternative sequenceiVSP_0431261 – 623Missing in isoform 6. 2 PublicationsAdd BLAST623
Alternative sequenceiVSP_008117596 – 620KTIRV…IALGE → CDRQEADYGRRGGQEDSRDG KASIG in isoform 4. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_044502599 – 638RVKIV…SPDVT → HIKVIDDEAYEKNKNYFIEM MGPRMVDMSFQKALLLSP in isoform 8. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_008118621 – 927Missing in isoform 4. 1 PublicationAdd BLAST307
Alternative sequenceiVSP_008116630 – 635Missing in isoform 2 and isoform 6. 3 Publications6
Alternative sequenceiVSP_043850636 – 638Missing in isoform 7. 1 Publication3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF510501 mRNA Translation: AAN60790.1
AF510502 mRNA Translation: AAN60791.1
AF510503 mRNA Translation: AAN60792.1
AF508982 Genomic DNA Translation: AAM90955.1
AJ304852 mRNA Translation: CAC40984.1
AJ304853 mRNA Translation: CAC40985.1
AJ745101 mRNA Translation: CAG33739.1
AJ745102 mRNA Translation: CAG33740.1
AL135747 Genomic DNA No translation available.
AL160191 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW81019.1
CH471061 Genomic DNA Translation: EAW81021.1
CH471061 Genomic DNA Translation: EAW81026.1
BC142969 mRNA Translation: AAI42970.1
X93017 Genomic DNA No translation available.
CCDSiCCDS35498.1 [P57103-1]
CCDS41967.1 [P57103-4]
CCDS45131.1 [P57103-5]
CCDS53904.1 [P57103-6]
CCDS9799.1 [P57103-7]
CCDS9800.1 [P57103-2]
RefSeqiNP_001123889.1, NM_001130417.2 [P57103-5]
NP_150287.1, NM_033262.4 [P57103-7]
NP_489479.1, NM_058240.3 [P57103-6]
NP_891977.1, NM_182932.2 [P57103-2]
NP_891981.1, NM_182936.2 [P57103-4]
NP_892114.1, NM_183002.2 [P57103-1]
XP_016877095.1, XM_017021606.1 [P57103-1]
XP_016877097.1, XM_017021608.1 [P57103-2]
UniGeneiHs.337696

Genome annotation databases

EnsembliENST00000216568; ENSP00000216568; ENSG00000100678 [P57103-5]
ENST00000356921; ENSP00000349392; ENSG00000100678 [P57103-2]
ENST00000357887; ENSP00000350560; ENSG00000100678 [P57103-7]
ENST00000381269; ENSP00000370669; ENSG00000100678 [P57103-1]
ENST00000394330; ENSP00000377863; ENSG00000100678 [P57103-4]
ENST00000494208; ENSP00000436332; ENSG00000100678 [P57103-3]
ENST00000528359; ENSP00000433531; ENSG00000100678 [P57103-7]
ENST00000534137; ENSP00000436688; ENSG00000100678 [P57103-6]
GeneIDi6547
KEGGihsa:6547
UCSCiuc001xlu.5 human [P57103-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNAC3_HUMAN
AccessioniPrimary (citable) accession number: P57103
Secondary accession number(s): Q5K3P6
, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2
Entry historyiIntegrated 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 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