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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi409 – 4091Calcium 1By similarity
Metal bindingi409 – 4091Calcium 2By similarity
Metal bindingi409 – 4091Calcium 3By similarity
Metal bindingi445 – 4451Calcium 1By similarity
Metal bindingi445 – 4451Calcium 4By similarity
Metal bindingi470 – 4701Calcium 2By similarity
Metal bindingi471 – 4711Calcium 1By similarity
Metal bindingi471 – 4711Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi471 – 4711Calcium 3By similarity
Metal bindingi471 – 4711Calcium 4By similarity
Metal bindingi473 – 4731Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi475 – 4751Calcium 1By similarity
Metal bindingi475 – 4751Calcium 3By similarity
Metal bindingi475 – 4751Calcium 4By similarity
Metal bindingi478 – 4781Calcium 4By similarity
Metal bindingi525 – 5251Calcium 3By similarity
Metal bindingi526 – 5261Calcium 2By similarity
Metal bindingi527 – 5271Calcium 2By similarity
Metal bindingi527 – 5271Calcium 3By similarity
Metal bindingi543 – 5431Calcium 5By similarity
Metal bindingi579 – 5791Calcium 6By similarity
Metal bindingi606 – 6061Calcium 6By similarity
Metal bindingi607 – 6071Calcium 5; via carbonyl oxygenBy similarity
Metal bindingi607 – 6071Calcium 6By similarity
Metal bindingi672 – 6721Calcium 5By similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 7343ExtracellularSequence analysisAdd
BLAST
Transmembranei74 – 9421HelicalSequence analysisAdd
BLAST
Topological domaini95 – 14753CytoplasmicSequence analysisAdd
BLAST
Transmembranei148 – 16821HelicalSequence analysisAdd
BLAST
Topological domaini169 – 1691ExtracellularSequence analysis
Transmembranei170 – 19021HelicalSequence analysisAdd
BLAST
Topological domaini191 – 20212CytoplasmicSequence analysisAdd
BLAST
Transmembranei203 – 22321HelicalSequence analysisAdd
BLAST
Topological domaini224 – 2307ExtracellularSequence analysis
Transmembranei231 – 25121HelicalSequence analysisAdd
BLAST
Topological domaini252 – 726475CytoplasmicSequence analysisAdd
BLAST
Transmembranei727 – 74721HelicalSequence analysisAdd
BLAST
Topological domaini748 – 7547ExtracellularSequence analysis
Transmembranei755 – 77521HelicalSequence analysisAdd
BLAST
Topological domaini776 – 7783CytoplasmicSequence analysis
Transmembranei779 – 79921HelicalSequence analysisAdd
BLAST
Topological domaini800 – 82829ExtracellularSequence analysisAdd
BLAST
Transmembranei829 – 84921HelicalSequence analysisAdd
BLAST
Topological domaini850 – 86011CytoplasmicSequence analysisAdd
BLAST
Transmembranei861 – 88121HelicalSequence analysisAdd
BLAST
Topological domaini882 – 90322ExtracellularSequence analysisAdd
BLAST
Transmembranei904 – 92421HelicalSequence analysisAdd
BLAST
Topological domaini925 – 9273CytoplasmicSequence analysis

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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030Sequence analysisAdd
BLAST
Chaini31 – 927897Sodium/calcium exchanger 3PRO_0000019385Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi45 – 451N-linked (GlcNAc...)Sequence analysis
Glycosylationi823 – 8231N-linked (GlcNAc...)Sequence analysis

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

GenevisibleiP70549. RN.

Interactioni

Subunit structurei

Interacts with AKAP1.By similarity

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP70549.
SMRiP70549. Positions 396-681.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati140 – 18041Alpha-1Add
BLAST
Domaini386 – 485100Calx-beta 1Add
BLAST
Domaini519 – 619101Calx-beta 2Add
BLAST
Repeati796 – 83237Alpha-2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni253 – 27220Putative calmodulin-binding regionBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi645 – 6484Poly-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.
InParanoidiP70549.
KOiK05849.
OMAiVHTDEPE.
OrthoDBiEOG7S4X56.

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.

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.

3D structure databases

ProteinModelPortaliP70549.
SMRiP70549. Positions 396-681.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP70549. 1 interaction.
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.
OrthoDBiEOG7S4X56.

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

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...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3)."
    Linck B., Qiu Z., He Z., Tong Q., Hilgemann D.W., Philipson K.D.
    Am. J. Physiol. 274:C415-C423(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
  3. "Cellular and subcellular localization of Na+-Ca2+ exchanger protein isoforms, NCX1, NCX2, and NCX3 in cerebral cortex and hippocampus of adult rat."
    Minelli A., Castaldo P., Gobbi P., Salucci S., Magi S., Amoroso S.
    Cell Calcium 41:221-234(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  4. "Silencing or knocking out the Na(+)/Ca(2+) exchanger-3 (NCX3) impairs oligodendrocyte differentiation."
    Boscia F., D'Avanzo C., Pannaccione A., Secondo A., Casamassa A., Formisano L., Guida N., Sokolow S., Herchuelz A., Annunziato L.
    Cell Death Differ. 19:562-572(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  5. "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.

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: June 8, 2016
This is version 115 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.