ID  S4R2P9;
PN  Sodium/calcium exchanger 3;
GN  Slc8a3;
OS  10090;
SL  Nucleus Position: SL-0198;
SL  Comments: Cell membrane {ECO:0000269|PubMed:14722618, ECO:0000269|PubMed:24101730}; Multi-pass membrane protein {ECO:0000305}. Perikaryon {ECO:0000250|UniProtKB:P70549}. Cell projection, dendrite {ECO:0000250|UniProtKB:P70549}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:P70549}. Cell membrane, sarcolemma {ECO:0000269|PubMed:14722618}. Cytoplasm, sarcoplasm {ECO:0000269|PubMed:14722618}. Cell junction {ECO:0000269|PubMed:14722618}. Mitochondrion outer membrane {ECO:0000269|PubMed:24101730}; Multi-pass membrane protein {ECO:0000305}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P57103}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:24101730}; Multi-pass membrane protein {ECO:0000305}. Note=Detected at neuromuscular junctions. {ECO:0000269|PubMed:14722618}. [Isoform 1]: Cell membrane {ECO:0000269|PubMed:24616101}; Multi-pass membrane protein {ECO:0000305}. [Isoform 2]: Cell membrane {ECO:0000269|PubMed:24616101}; Multi-pass membrane protein {ECO:0000305}.
DR  UNIPROT: S4R2P9;
DR  UNIPROT: Q7TS90;
DR  UNIPROT: Q8VHJ8;
DR  PDB: 2LT9;
DR  Pfam: PF03160;
DR  Pfam: PF01699;
DR  Pfam: PF16494;
DE  Function: Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes. Contributes to cellular Ca(2+) homeostasis in excitable cells, both in muscle and in brain (PubMed:14722618, PubMed:21593315). In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A3 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline (PubMed:14722618, PubMed:21593315). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle (PubMed:14722618). In neurons, contributes to the rapid decrease of cytoplasmic Ca(2+) levels back to baseline after neuronal activation, and thereby contributes to modulate synaptic plasticity, learning and memory (PubMed:21593315). Required for normal oligodendrocyte differentiation and for normal myelination (PubMed:21959935). Mediates Ca(2+) efflux from mitochondria and contributes to mitochondrial Ca(2+) ion homeostasis (PubMed:24616101). Isoform 1 displays higher calcium exchanger activity than isoform 2, probably because isoform 1 has a lower threshold for activation by cytoplasmic Ca(2+) (PubMed:24616101). {ECO:0000269|PubMed:14722618, ECO:0000269|PubMed:21593315, ECO:0000269|PubMed:21959935, ECO:0000269|PubMed:24616101}.
DE  Reference Proteome: Yes;
GO  GO:0070161;
GO  GO:0030424;
GO  GO:0043679;
GO  GO:0042995;
GO  GO:0030425;
GO  GO:0043197;
GO  GO:0005789;
GO  GO:0005887;
GO  GO:0099055;
GO  GO:0031226;
GO  GO:0016020;
GO  GO:0005874;
GO  GO:0005741;
GO  GO:0005739;
GO  GO:0031594;
GO  GO:0043025;
GO  GO:0043204;
GO  GO:0048471;
GO  GO:0005886;
GO  GO:0098794;
GO  GO:0014069;
GO  GO:0042383;
GO  GO:0016528;
GO  GO:0045202;
GO  GO:0015368;
GO  GO:1905060;
GO  GO:0005432;
GO  GO:0005516;
GO  GO:0099580;
GO  GO:0046872;
GO  GO:1990034;
GO  GO:0098703;
GO  GO:0070588;
GO  GO:0060402;
GO  GO:0007154;
GO  GO:0006874;
GO  GO:0071320;
GO  GO:0071456;
GO  GO:0002244;
GO  GO:0007612;
GO  GO:0007611;
GO  GO:0060291;
GO  GO:0007613;
GO  GO:0030001;
GO  GO:0051560;
GO  GO:0006851;
GO  GO:0098815;
GO  GO:0042552;
GO  GO:0071901;
GO  GO:0048709;
GO  GO:0014819;
GO  GO:0035725;
GO  GO:0006814;
GO  GO:0050808;
TP  Membrane Topology: Transmembrane; Source: UniProt - Sequence Analysis {ECO:0000255};
SQ  MAWLRLQPLTSAFLHFGLVTFVLFLNCLRAEAGDSGDVPSAGQNNESCSGSSDCKEGVILPIWYPENPSLGDKIARVIVY
SQ  FVALIYMFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGF
SQ  IAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRVFFVTAAWSIFAYIWLYMILAVFSPGVVQVWEGLLTLFF
SQ  FPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFLDGNFTPLEGKEVDESRREMIRIL
SQ  KDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQAKKTSSMSEVHTDEPEDFASKVFF
SQ  DPCSYQCLENCGAVLLTVVRKGGDISKTMYVDYKTEDGSANAGADYEFTEGTVVLKPGETQKEFSVGIIDDDIFEEDEHF
SQ  FVRLSNVRVEEEQLAEGMLPAILNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSESIGVMEVKVLRTSGARG
SQ  TVIVPFRTVEGTAKGGGEDFEDAYGELEFKNDETVKTIHIKVIDDKAYEKNKNYVIEMMGPRMVDMSVQKALLLSPEVTD
SQ  RKLTVEEEEAKRIAEMGKPVLGEHPKLEVIIEESYEFKSTVDKLIKKTNLALVVGTHSWRDQFMEAITVSAGGDEDEDES
SQ  GEERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWACFVVSILIIGMLTAIIGDLASHFGCTIGLKDSVTAVVFVAFGT
SQ  SVPDTFASKAAALQDVYADASIGNVTGSNAVNVFLGIGLAWSVAAIYWAMQGQEFHVSAGTLAFSVTLFTIFAFVCLSVL
SQ  LYRRRPHLGGELGGPRGCKLATTWLFVSLWLLYILFATLEAYCYIKGF
//