Q925Q3 · NCLX_MOUSE
- ProteinMitochondrial sodium/calcium exchanger protein
- GeneSlc8b1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids585 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
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).
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).
Catalytic activity
- Ca2+(in) + 3 Na+(out) = Ca2+(out) + 3 Na+(in)
- Ca2+(in) + 3 Li+(out) = Ca2+(out) + 3 Li+(in)
Activity regulation
Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:28445457).
Strongly inhibited by zinc (By similarity).
Strongly inhibited by zinc (By similarity).
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMitochondrial sodium/calcium exchanger protein
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ925Q3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Multi-pass membrane protein
Note: Mainly localizes to mitochondrion inner membrane (PubMed:20018762).
Isoform 2
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 27-95 | Extracellular | ||||
Sequence: TGDPSTKAHGHIQFSAGSVNQTAMADCRAVCGLNTSDRCDFVRRNPDCRSEAGYLDYLEGIFCYFPPNL | ||||||
Transmembrane | 96-116 | Helical; Name=1 | ||||
Sequence: LPLAITLYVFWLLYLFLILGV | ||||||
Topological domain | 117-140 | Cytoplasmic | ||||
Sequence: TAAKFFCPNLSAISTNLKLSHNVA | ||||||
Transmembrane | 141-161 | Helical; Name=2 | ||||
Sequence: GVTFLAFGNGAPDIFSALVAF | ||||||
Topological domain | 162-168 | Extracellular | ||||
Sequence: SDPRTAG | ||||||
Transmembrane | 169-189 | Helical; Name=3 | ||||
Sequence: LAIGALFGAGVLVTTVVAGGI | ||||||
Topological domain | 190-205 | Cytoplasmic | ||||
Sequence: TILHPFMAASRPFLRD | ||||||
Transmembrane | 206-226 | Helical; Name=4 | ||||
Sequence: IAFYMVAVFLTFTALYLGRIT | ||||||
Topological domain | 227-229 | Extracellular | ||||
Sequence: LTW | ||||||
Transmembrane | 230-250 | Helical; Name=5 | ||||
Sequence: ALGYLGLYVFYVVTVIICTWV | ||||||
Topological domain | 251-325 | Cytoplasmic | ||||
Sequence: YQRQRSRSLVHSISETPELLSESEEDQMSSNTNSYDYGDEYRPLLLGRETTVQILIQALNPLDYRKWRTQSISWR | ||||||
Transmembrane | 326-346 | Helical; Name=6 | ||||
Sequence: VLKVVKLPVEFLLLLTVPVVD | ||||||
Topological domain | 347-360 | Extracellular | ||||
Sequence: PDKDDRNWKRPLNC | ||||||
Transmembrane | 361-381 | Helical; Name=7 | ||||
Sequence: LQLVISPLVLVLTLQSGVYGI | ||||||
Topological domain | 382-383 | Cytoplasmic | ||||
Sequence: YE | ||||||
Transmembrane | 384-404 | Helical; Name=8 | ||||
Sequence: IGGLLPVWAVVVIVGTALASV | ||||||
Topological domain | 405-416 | Extracellular | ||||
Sequence: TFFATSNREPPR | ||||||
Transmembrane | 417-437 | Helical; Name=9 | ||||
Sequence: LHWLFAFLGFLTSALWINAAA | ||||||
Topological domain | 438-445 | Cytoplasmic | ||||
Sequence: TEVVNILR | ||||||
Transmembrane | 446-466 | Helical; Name=10 | ||||
Sequence: SLGVIFRLSNTVLGLTLLAWG | ||||||
Topological domain | 467-491 | Extracellular | ||||
Sequence: NSIGDAFSDFTLARQGYPRMAFSAC | ||||||
Transmembrane | 492-512 | Helical; Name=11 | ||||
Sequence: FGGIIFNILVGVGLGCLLQII | ||||||
Topological domain | 513-525 | Cytoplasmic | ||||
Sequence: RNHVVEVKLEPDG | ||||||
Transmembrane | 526-546 | Helical; Name=12 | ||||
Sequence: LLVWVLASALGLSLIFSLVSV | ||||||
Topological domain | 547-559 | Extracellular | ||||
Sequence: PLQCFQLSKAYGL | ||||||
Transmembrane | 560-580 | Helical; Name=13 | ||||
Sequence: CLLLFYICFLVVVLLTEFGVI | ||||||
Topological domain | 581-585 | Cytoplasmic | ||||
Sequence: HLKKA |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
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.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 41 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-26 | |||||
Sequence: MASRWLALLWAPVFLCVALILETASG | ||||||
Chain | PRO_0000045757 | 27-585 | Mitochondrial sodium/calcium exchanger protein | |||
Sequence: TGDPSTKAHGHIQFSAGSVNQTAMADCRAVCGLNTSDRCDFVRRNPDCRSEAGYLDYLEGIFCYFPPNLLPLAITLYVFWLLYLFLILGVTAAKFFCPNLSAISTNLKLSHNVAGVTFLAFGNGAPDIFSALVAFSDPRTAGLAIGALFGAGVLVTTVVAGGITILHPFMAASRPFLRDIAFYMVAVFLTFTALYLGRITLTWALGYLGLYVFYVVTVIICTWVYQRQRSRSLVHSISETPELLSESEEDQMSSNTNSYDYGDEYRPLLLGRETTVQILIQALNPLDYRKWRTQSISWRVLKVVKLPVEFLLLLTVPVVDPDKDDRNWKRPLNCLQLVISPLVLVLTLQSGVYGIYEIGGLLPVWAVVVIVGTALASVTFFATSNREPPRLHWLFAFLGFLTSALWINAAATEVVNILRSLGVIFRLSNTVLGLTLLAWGNSIGDAFSDFTLARQGYPRMAFSACFGGIIFNILVGVGLGCLLQIIRNHVVEVKLEPDGLLVWVLASALGLSLIFSLVSVPLQCFQLSKAYGLCLLLFYICFLVVVLLTEFGVIHLKKA | ||||||
Glycosylation | 46 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 258 | Phosphoserine; by PKA | ||||
Sequence: S |
Post-translational modification
Phosphorylation at Ser-258 by PKA prevents calcium overload.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed. Expressed in dental tissues.
Gene expression databases
Structure
Family & Domains
Sequence similarities
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
Q925Q3-1
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.
- Name1
- SynonymsL, Long
- Length585
- Mass (Da)64,365
- Last updated2006-01-10 v2
- Checksum83B001A9C78B2620
Q925Q3-2
- Name2
- SynonymsS, Short
- Differences from canonical
- 471-585: DAFSDFTLARQGYPRMAFSACFGGIIFNILVGVGLGCLLQIIRNHVVEVKLEPDGLLVWVLASALGLSLIFSLVSVPLQCFQLSKAYGLCLLLFYICFLVVVLLTEFGVIHLKKA → AGARRITGVGAGQCPGPQLDLLPGLRAASVFPAQQGLRPLPPPLLHLFPCCGPAHRVWGDSPEEGVTEAAWPRGVGAILLAS
Q925Q3-3
- Name3
- Differences from canonical
- 122-140: FCPNLSAISTNLKLSHNVA → PH
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 20 | in Ref. 1; AAK49407 | ||||
Sequence: I → L | ||||||
Alternative sequence | VSP_016997 | 122-140 | in isoform 3 | |||
Sequence: FCPNLSAISTNLKLSHNVA → PH | ||||||
Sequence conflict | 228 | in Ref. 1; AAK49407 | ||||
Sequence: T → A | ||||||
Sequence conflict | 298 | in Ref. 1; AAK49407 | ||||
Sequence: R → Q | ||||||
Sequence conflict | 381 | in Ref. 1; AAK49407 | ||||
Sequence: I → L | ||||||
Sequence conflict | 451 | in Ref. 1; AAK49407 | ||||
Sequence: F → L | ||||||
Alternative sequence | VSP_016998 | 471-585 | in isoform 2 | |||
Sequence: DAFSDFTLARQGYPRMAFSACFGGIIFNILVGVGLGCLLQIIRNHVVEVKLEPDGLLVWVLASALGLSLIFSLVSVPLQCFQLSKAYGLCLLLFYICFLVVVLLTEFGVIHLKKA → AGARRITGVGAGQCPGPQLDLLPGLRAASVFPAQQGLRPLPPPLLHLFPCCGPAHRVWGDSPEEGVTEAAWPRGVGAILLAS | ||||||
Sequence conflict | 566 | in Ref. 1; AAK49407 | ||||
Sequence: I → V |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF261233 EMBL· GenBank· DDBJ | AAK49407.1 EMBL· GenBank· DDBJ | mRNA | ||
AK157173 EMBL· GenBank· DDBJ | BAE33988.1 EMBL· GenBank· DDBJ | mRNA | ||
BC043689 EMBL· GenBank· DDBJ | AAH43689.1 EMBL· GenBank· DDBJ | mRNA |