UniProtKB - Q925Q3 (NCLX_MOUSE)
Protein
Mitochondrial sodium/calcium exchanger protein
Gene
Slc8b1
Organism
Mus musculus (Mouse)
Status
Functioni
Mitochondrial sodium/calcium antiporter that mediates sodium-dependent calcium efflux from mitochondrion, by mediating the exchange of 3 sodium ions per 1 calcium ion (PubMed:20018762, PubMed:28445457). Plays a central role in mitochondrial calcium homeostasis by mediating mitochondrial calcium extrusion: calcium efflux is essential for mitochondrial function and cell survival, notably in cardiomyocytes (PubMed:24067497, PubMed:28445457). Regulates rates of glucose-dependent insulin secretion in pancreatic beta-cells during the first phase of insulin secretion: acts by mediating efflux of calcium from mitochondrion, thereby affecting cytoplasmic calcium responses (By similarity). Required for store-operated Ca2+ entry (SOCE) and Ca2+ release-activated Ca2+ (CRAC) channel regulation: sodium transport by SLC8B1 leads to promote calcium-shuttling that modulates mitochondrial redox status, thereby regulating SOCE activity (By similarity). Involved in B-lymphocyte chemotaxis (PubMed:27328625). Able to transport Ca2+ in exchange of either Li+ or Na+, explaining how Li+ catalyzes Ca2+ exchange (By similarity). In contrast to other members of the family its function is independent of K+ (By similarity).By similarity4 Publications
Caution
Isoform 1 was reported to not have cation exchanger activity (PubMed:12080145). However, such result is unclear.1 Publication
Isoform 1 and isoform 2 were reported to localize to the endoplasmic reticulum membrane and cell membrane, respectively (PubMed:14625281). This result is however not supported by other studies that report localization to the mitochondrial membrane (PubMed:20018762, PubMed:24067497).3 Publications
Activity regulationi
Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:28445457). Strongly inhibited by zinc (By similarity).By similarity
GO - Molecular functioni
- calcium:sodium antiporter activity Source: BHF-UCL
- calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential Source: UniProtKB
- cation transmembrane transporter activity Source: GO_Central
- identical protein binding Source: MGI
- protein homodimerization activity Source: BHF-UCL
GO - Biological processi
- calcium export from the mitochondrion Source: UniProtKB
- calcium ion transmembrane transport Source: MGI
- cation transport Source: GO_Central
- cellular calcium ion homeostasis Source: GO_Central
- glucose homeostasis Source: UniProtKB
- mitochondrial calcium ion homeostasis Source: BHF-UCL
- mitochondrial calcium ion transmembrane transport Source: MGI
- regulation of cardiac muscle cell membrane potential Source: BHF-UCL
- regulation of cytosolic calcium ion concentration Source: BHF-UCL
- regulation of insulin secretion Source: UniProtKB
- regulation of lymphocyte chemotaxis Source: UniProtKB
- regulation of store-operated calcium entry Source: MGI
- response to stimulus Source: UniProtKB-KW
- sodium ion transmembrane transport Source: MGI
Keywordsi
Biological process | Antiport, Calcium transport, Ion transport, Sensory transduction, Sodium transport, Transport |
Ligand | Calcium, Lithium, Sodium |
Enzyme and pathway databases
Reactomei | R-MMU-425561, Sodium/Calcium exchangers R-MMU-8949215, Mitochondrial calcium ion transport |
Names & Taxonomyi
Protein namesi | Recommended name: Mitochondrial sodium/calcium exchanger proteinCuratedAlternative name(s): Na(+)/K(+)/Ca(2+)-exchange protein 61 Publication Sodium/calcium exchanger protein, mitochondrial1 Publication Sodium/potassium/calcium exchanger 61 Publication Solute carrier family 24 member 6Imported Solute carrier family 8 member B1Imported |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2180781, Slc8b1 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane 2 Publications; Multi-pass membrane protein 1 Publication
Note: Mainly localizes to mitochondrion inner membrane (PubMed:20018762).
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Mitochondrion
- integral component of mitochondrial membrane Source: UniProtKB
- mitochondrial crista Source: BHF-UCL
- mitochondrial inner membrane Source: MGI
- mitochondrion Source: UniProtKB
Plasma Membrane
- plasma membrane Source: MGI
- sarcolemma Source: MGI
Other locations
- membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 27 – 95 | ExtracellularSequence analysisAdd BLAST | 69 | |
Transmembranei | 96 – 116 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 117 – 140 | CytoplasmicSequence analysisAdd BLAST | 24 | |
Transmembranei | 141 – 161 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 162 – 168 | ExtracellularSequence analysis | 7 | |
Transmembranei | 169 – 189 | Helical; Name=3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 190 – 205 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 206 – 226 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 227 – 229 | ExtracellularSequence analysis | 3 | |
Transmembranei | 230 – 250 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 251 – 325 | CytoplasmicSequence analysisAdd BLAST | 75 | |
Transmembranei | 326 – 346 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 347 – 360 | ExtracellularSequence analysisAdd BLAST | 14 | |
Transmembranei | 361 – 381 | Helical; Name=7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 382 – 383 | CytoplasmicSequence analysis | 2 | |
Transmembranei | 384 – 404 | Helical; Name=8Sequence analysisAdd BLAST | 21 | |
Topological domaini | 405 – 416 | ExtracellularSequence analysisAdd BLAST | 12 | |
Transmembranei | 417 – 437 | Helical; Name=9Sequence analysisAdd BLAST | 21 | |
Topological domaini | 438 – 445 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 446 – 466 | Helical; Name=10Sequence analysisAdd BLAST | 21 | |
Topological domaini | 467 – 491 | ExtracellularSequence analysisAdd BLAST | 25 | |
Transmembranei | 492 – 512 | Helical; Name=11Sequence analysisAdd BLAST | 21 | |
Topological domaini | 513 – 525 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Transmembranei | 526 – 546 | Helical; Name=12Sequence analysisAdd BLAST | 21 | |
Topological domaini | 547 – 559 | ExtracellularSequence analysisAdd BLAST | 13 | |
Transmembranei | 560 – 580 | Helical; Name=13Sequence analysisAdd BLAST | 21 | |
Topological domaini | 581 – 585 | CytoplasmicSequence analysis | 5 |
Keywords - Cellular componenti
Cell membrane, Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Disruption phenotypei
Conditional deletion in adult hearts causes sudden death in 87% of the mice. Hearts show substantial cardiac remodeling, including an increase in heart mass and correlative change in cardiomyocyte cross-sectional area, as well as a significant increase in cardiac fibrosis. Defects are probably due to mitochondrial calcium overload leading to increased generation of superoxide and necrotic cell death.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 26 | MitochondrionSequence analysisAdd BLAST | 26 | |
ChainiPRO_0000045757 | 27 – 585 | Mitochondrial sodium/calcium exchanger proteinAdd BLAST | 559 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 46 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 258 | Phosphoserine; by PKABy similarity | 1 |
Post-translational modificationi
Phosphorylation at Ser-258 by PKA prevents calcium overload.By similarity
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | Q925Q3 |
PaxDbi | Q925Q3 |
PRIDEi | Q925Q3 |
PTM databases
GlyGeni | Q925Q3, 1 site |
PhosphoSitePlusi | Q925Q3 |
SwissPalmi | Q925Q3 |
Expressioni
Tissue specificityi
Ubiquitously expressed. Expressed in dental tissues.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000032754, Expressed in liver and 230 other tissues |
Genevisiblei | Q925Q3, MM |
Interactioni
GO - Molecular functioni
- identical protein binding Source: MGI
- protein homodimerization activity Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 228418, 5 interactors |
STRINGi | 10090.ENSMUSP00000064714 |
Miscellaneous databases
RNActi | Q925Q3, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily. [View classification]Curated
Keywords - Domaini
Transit peptide, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2399, Eukaryota |
GeneTreei | ENSGT00940000157433 |
HOGENOMi | CLU_004979_3_2_1 |
InParanoidi | Q925Q3 |
OMAi | CAFVKRT |
OrthoDBi | 478735at2759 |
PhylomeDBi | Q925Q3 |
TreeFami | TF323444 |
Family and domain databases
InterProi | View protein in InterPro IPR004837, NaCa_Exmemb |
Pfami | View protein in Pfam PF01699, Na_Ca_ex, 2 hits |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q925Q3-1) [UniParc]FASTAAdd to basket
Also known as: L1 Publication, Long1 Publication
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MASRWLALLW APVFLCVALI LETASGTGDP STKAHGHIQF SAGSVNQTAM
60 70 80 90 100
ADCRAVCGLN TSDRCDFVRR NPDCRSEAGY LDYLEGIFCY FPPNLLPLAI
110 120 130 140 150
TLYVFWLLYL FLILGVTAAK FFCPNLSAIS TNLKLSHNVA GVTFLAFGNG
160 170 180 190 200
APDIFSALVA FSDPRTAGLA IGALFGAGVL VTTVVAGGIT ILHPFMAASR
210 220 230 240 250
PFLRDIAFYM VAVFLTFTAL YLGRITLTWA LGYLGLYVFY VVTVIICTWV
260 270 280 290 300
YQRQRSRSLV HSISETPELL SESEEDQMSS NTNSYDYGDE YRPLLLGRET
310 320 330 340 350
TVQILIQALN PLDYRKWRTQ SISWRVLKVV KLPVEFLLLL TVPVVDPDKD
360 370 380 390 400
DRNWKRPLNC LQLVISPLVL VLTLQSGVYG IYEIGGLLPV WAVVVIVGTA
410 420 430 440 450
LASVTFFATS NREPPRLHWL FAFLGFLTSA LWINAAATEV VNILRSLGVI
460 470 480 490 500
FRLSNTVLGL TLLAWGNSIG DAFSDFTLAR QGYPRMAFSA CFGGIIFNIL
510 520 530 540 550
VGVGLGCLLQ IIRNHVVEVK LEPDGLLVWV LASALGLSLI FSLVSVPLQC
560 570 580
FQLSKAYGLC LLLFYICFLV VVLLTEFGVI HLKKA
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3Z226 | D3Z226_MOUSE | Mitochondrial sodium/calcium exchan... | Slc8b1 Slc24a6 | 529 | Annotation score: | ||
D3Z5E7 | D3Z5E7_MOUSE | Mitochondrial sodium/calcium exchan... | Slc8b1 Slc24a6 | 92 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 20 | I → L in AAK49407 (PubMed:12080145).Curated | 1 | |
Sequence conflicti | 228 | T → A in AAK49407 (PubMed:12080145).Curated | 1 | |
Sequence conflicti | 298 | R → Q in AAK49407 (PubMed:12080145).Curated | 1 | |
Sequence conflicti | 381 | I → L in AAK49407 (PubMed:12080145).Curated | 1 | |
Sequence conflicti | 451 | F → L in AAK49407 (PubMed:12080145).Curated | 1 | |
Sequence conflicti | 566 | I → V in AAK49407 (PubMed:12080145).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016997 | 122 – 140 | FCPNL…SHNVA → PH in isoform 3. 1 PublicationAdd BLAST | 19 | |
Alternative sequenceiVSP_016998 | 471 – 585 | DAFSD…HLKKA → AGARRITGVGAGQCPGPQLD LLPGLRAASVFPAQQGLRPL PPPLLHLFPCCGPAHRVWGD SPEEGVTEAAWPRGVGAILL AS in isoform 2. 1 PublicationAdd BLAST | 115 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF261233 mRNA Translation: AAK49407.1 AK157173 mRNA Translation: BAE33988.1 BC043689 mRNA Translation: AAH43689.1 |
CCDSi | CCDS39238.1 [Q925Q3-1] CCDS51633.1 [Q925Q3-2] CCDS51634.1 [Q925Q3-3] |
RefSeqi | NP_001171065.1, NM_001177594.1 [Q925Q3-3] NP_001171066.1, NM_001177595.1 [Q925Q3-2] NP_573484.2, NM_133221.2 [Q925Q3-1] |
Genome annotation databases
Ensembli | ENSMUST00000068326; ENSMUSP00000064714; ENSMUSG00000032754 [Q925Q3-1] ENSMUST00000076051; ENSMUSP00000075428; ENSMUSG00000032754 [Q925Q3-2] ENSMUST00000111890; ENSMUSP00000107521; ENSMUSG00000032754 [Q925Q3-3] |
GeneIDi | 170756 |
KEGGi | mmu:170756 |
UCSCi | uc008zhj.2, mouse [Q925Q3-1] uc012eco.1, mouse [Q925Q3-3] uc012ecp.1, mouse [Q925Q3-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF261233 mRNA Translation: AAK49407.1 AK157173 mRNA Translation: BAE33988.1 BC043689 mRNA Translation: AAH43689.1 |
CCDSi | CCDS39238.1 [Q925Q3-1] CCDS51633.1 [Q925Q3-2] CCDS51634.1 [Q925Q3-3] |
RefSeqi | NP_001171065.1, NM_001177594.1 [Q925Q3-3] NP_001171066.1, NM_001177595.1 [Q925Q3-2] NP_573484.2, NM_133221.2 [Q925Q3-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 228418, 5 interactors |
STRINGi | 10090.ENSMUSP00000064714 |
PTM databases
GlyGeni | Q925Q3, 1 site |
PhosphoSitePlusi | Q925Q3 |
SwissPalmi | Q925Q3 |
Proteomic databases
jPOSTi | Q925Q3 |
PaxDbi | Q925Q3 |
PRIDEi | Q925Q3 |
Protocols and materials databases
Antibodypediai | 31257, 85 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000068326; ENSMUSP00000064714; ENSMUSG00000032754 [Q925Q3-1] ENSMUST00000076051; ENSMUSP00000075428; ENSMUSG00000032754 [Q925Q3-2] ENSMUST00000111890; ENSMUSP00000107521; ENSMUSG00000032754 [Q925Q3-3] |
GeneIDi | 170756 |
KEGGi | mmu:170756 |
UCSCi | uc008zhj.2, mouse [Q925Q3-1] uc012eco.1, mouse [Q925Q3-3] uc012ecp.1, mouse [Q925Q3-2] |
Organism-specific databases
CTDi | 80024 |
MGIi | MGI:2180781, Slc8b1 |
Phylogenomic databases
eggNOGi | KOG2399, Eukaryota |
GeneTreei | ENSGT00940000157433 |
HOGENOMi | CLU_004979_3_2_1 |
InParanoidi | Q925Q3 |
OMAi | CAFVKRT |
OrthoDBi | 478735at2759 |
PhylomeDBi | Q925Q3 |
TreeFami | TF323444 |
Enzyme and pathway databases
Reactomei | R-MMU-425561, Sodium/Calcium exchangers R-MMU-8949215, Mitochondrial calcium ion transport |
Miscellaneous databases
BioGRID-ORCSi | 170756, 1 hit in 18 CRISPR screens |
ChiTaRSi | Slc8b1, mouse |
PROi | PR:Q925Q3 |
RNActi | Q925Q3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000032754, Expressed in liver and 230 other tissues |
Genevisiblei | Q925Q3, MM |
Family and domain databases
InterProi | View protein in InterPro IPR004837, NaCa_Exmemb |
Pfami | View protein in Pfam PF01699, Na_Ca_ex, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NCLX_MOUSE | |
Accessioni | Q925Q3Primary (citable) accession number: Q925Q3 Secondary accession number(s): Q3U067, Q80XM7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 10, 2006 |
Last sequence update: | January 10, 2006 | |
Last modified: | December 2, 2020 | |
This is version 127 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families