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Protein

Sodium/calcium exchanger 3

Gene

Slc8a3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (PubMed:8798769, PubMed:9486131). 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. Required for normal oligodendrocyte differentiation and for normal myelination. Mediates Ca2+ efflux from mitochondria and contributes to mitochondrial Ca2+ ion homeostasis.By similarity2 Publications

Enzyme regulationi

Calcium transport is down-regulated by Na+ and stimulated by Ca2+.1 Publication

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

  • calcium:sodium antiporter activity Source: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • calcium ion export from cell Source: RGD
  • calcium ion import into cell Source: RGD
  • calcium ion transport into cytosol Source: RGD
  • cell communication Source: InterPro
  • cellular response to cAMP Source: RGD
  • cellular response to hypoxia Source: UniProtKB
  • hematopoietic progenitor cell differentiation Source: Ensembl
  • learning Source: UniProtKB
  • long-term synaptic potentiation Source: UniProtKB
  • memory Source: UniProtKB
  • mitochondrial calcium ion homeostasis Source: UniProtKB
  • mitochondrial calcium ion transport Source: UniProtKB
  • myelination Source: UniProtKB
  • oligodendrocyte differentiation Source: UniProtKB
  • regulation of skeletal muscle contraction Source: UniProtKB
  • sodium ion transport Source: RGD
  • telencephalon development Source: RGD
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-RNO-418359. Reduction of cytosolic Ca++ levels.
R-RNO-425561. Sodium/Calcium exchangers.
R-RNO-5578775. Ion homeostasis.

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:Ncx31 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi620197. Slc8a3.

Subcellular locationi

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

GO - Cellular componenti

  • cell junction Source: UniProtKB-SubCell
  • cell projection Source: RGD
  • dendritic spine Source: RGD
  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • microtubule Source: RGD
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: RGD
  • neuromuscular junction Source: UniProtKB
  • neuronal cell body Source: RGD
  • perikaryon Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: RGD
  • sarcolemma Source: RGD
  • sarcoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000001938531 – 927Sodium/calcium exchanger 3Add BLAST897

Amino acid modifications

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

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP70549.
PRIDEiP70549.

Expressioni

Tissue specificityi

Detected in neurons in brain cortex and hippocampus. Detected in pyramidal cell bodies and processes, in granule cells and interneurons in the CA1 and CA3 region of the hippocampus. Detected on astrocyte processes in brain cortex. Detected on endothelial cells in hippocampus capillaries (at protein level) (PubMed:16914199). Restricted to brain and skeletal muscle (PubMed:8798769).2 Publications

Developmental stagei

Up-regulated during in vitro differentiation of oligodendrocytes (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000029871.
GenevisibleiP70549. RN.

Interactioni

Subunit structurei

Interacts with AKAP1.By similarity

Protein-protein interaction databases

IntActiP70549. 1 interactor.
MINTiMINT-8290546.
STRINGi10116.ENSRNOP00000041987.

Structurei

3D structure databases

ProteinModelPortaliP70549.
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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi645 – 648Poly-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.
InParanoidiP70549.
KOiK05849.
OMAiVHTDEPE.
OrthoDBiEOG091G0EC1.

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.

P70549-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAWLRLQPLT SAFLHFGLVT FVLFLNGLRA EAGDLRDVPS AGQNNESCSG
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
RVFFVTAAWS VFAYIWLYMI LAVFSPGVVQ VWEGLLTLFF FPVCVLLAWV
260 270 280 290 300
ADKRLLFYKY MHKRYRTDKH RGIIIETEGE HPKGIEMDGK MMNSHFLDGN
310 320 330 340 350
LIPLEGKEVD ESRREMIRIL KDLKQKHPEK DLDQLVEMAN YYALSHQQKS
360 370 380 390 400
RAFYRIQATR MMTGAGNILK KHAAEQAKKT ASMSEVHTDE PEDFASKVFF
410 420 430 440 450
DPCSYQCLEN CGAVLLTVVR KGGDISKTMY VDYKTEDGSA NAGADYEFTE
460 470 480 490 500
GTVVLKPGET QKEFSVGIID DDIFEEDEHF FVRLSNVRVE EEQLEEGMTP
510 520 530 540 550
AILNSLPLPR AVLASPCVAT VTILDDDHAG IFTFECDTIH VSESIGVMEV
560 570 580 590 600
KVLRTSGARG TVIVPFRTVE GTAKGGGEDF EDTYGELEFK NDETVKTIRV
610 620 630 640 650
KIVDEEEYER QENFFIALGE PKWMERGISA LLLSPEVTDR KLTMEEEEAK
660 670 680 690 700
RIAEMGKPVL GEHPKLEVII EESYEFKSTV DKLIKKTNLA LVVGTHSWRD
710 720 730 740 750
QFMEAITVSA AGDEEEDESG EERLPSCFDY VMHFLTVFWK VLFACVPPTE
760 770 780 790 800
YCHGWACFVV SILIIGMLTA IIGDLASHFG CTIGLKDSVT AVVFVAFGTS
810 820 830 840 850
VPDTFASKAA ALQDVYADAS IGNVTGSNAV NVFLGIGLAW SVAAIYWAMQ
860 870 880 890 900
GQEFHVSAGT LAFSVTLFTI FAFVCLSVLL YRRRPHLGGE LGGPRGCKLA
910 920
TTWLFVSLWL LYVLFATLEA YCYIKGF
Length:927
Mass (Da):103,163
Last modified:February 1, 1997 - v1
Checksum:iEAB35F9620DBE69E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53420 mRNA. Translation: AAC52817.1.
RefSeqiNP_511175.1. NM_078620.2.
XP_017449476.1. XM_017593987.1.
XP_017449477.1. XM_017593988.1.
XP_017449478.1. XM_017593989.1.
XP_017449479.1. XM_017593990.1.
XP_017449480.1. XM_017593991.1.

Genome annotation databases

EnsembliENSRNOT00000048606; ENSRNOP00000041987; ENSRNOG00000029871.
GeneIDi140448.
KEGGirno:140448.
UCSCiRGD:620197. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53420 mRNA. Translation: AAC52817.1.
RefSeqiNP_511175.1. NM_078620.2.
XP_017449476.1. XM_017593987.1.
XP_017449477.1. XM_017593988.1.
XP_017449478.1. XM_017593989.1.
XP_017449479.1. XM_017593990.1.
XP_017449480.1. XM_017593991.1.

3D structure databases

ProteinModelPortaliP70549.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP70549. 1 interactor.
MINTiMINT-8290546.
STRINGi10116.ENSRNOP00000041987.

Proteomic databases

PaxDbiP70549.
PRIDEiP70549.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000048606; ENSRNOP00000041987; ENSRNOG00000029871.
GeneIDi140448.
KEGGirno:140448.
UCSCiRGD:620197. rat.

Organism-specific databases

CTDi6547.
RGDi620197. Slc8a3.

Phylogenomic databases

eggNOGiKOG1306. Eukaryota.
ENOG410XPJP. LUCA.
GeneTreeiENSGT00730000110414.
HOGENOMiHOG000266971.
HOVERGENiHBG006441.
InParanoidiP70549.
KOiK05849.
OMAiVHTDEPE.
OrthoDBiEOG091G0EC1.

Enzyme and pathway databases

ReactomeiR-RNO-418359. Reduction of cytosolic Ca++ levels.
R-RNO-425561. Sodium/Calcium exchangers.
R-RNO-5578775. Ion homeostasis.

Miscellaneous databases

PROiP70549.

Gene expression databases

BgeeiENSRNOG00000029871.
GenevisibleiP70549. RN.

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 nameiNAC3_RAT
AccessioniPrimary (citable) accession number: P70549
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: November 30, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.