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Protein

Mitochondrial sodium/calcium exchanger protein

Gene

Slc8b1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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

Enzyme 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
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • calcium ion transmembrane transport Source: MGI
  • glucose homeostasis Source: UniProtKB
  • mitochondrial calcium ion homeostasis Source: BHF-UCL
  • mitochondrial calcium ion transmembrane transport Source: MGI
  • mitochondrial calcium release Source: UniProtKB
  • 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 processAntiport, Calcium transport, Ion transport, Sensory transduction, Sodium transport, Transport
LigandCalcium, Lithium, Sodium

Enzyme and pathway databases

ReactomeiR-MMU-425561. Sodium/Calcium exchangers.
R-MMU-8949215. Mitochondrial calcium ion transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial sodium/calcium exchanger proteinCurated
Alternative 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
Name:Slc8b1Imported
Synonyms:Nckx61 Publication, Nclx1 Publication, Slc24a6Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2180781. Slc8b1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 95ExtracellularSequence analysisAdd BLAST69
Transmembranei96 – 116Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini117 – 140CytoplasmicSequence analysisAdd BLAST24
Transmembranei141 – 161Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini162 – 168ExtracellularSequence analysis7
Transmembranei169 – 189Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini190 – 205CytoplasmicSequence analysisAdd BLAST16
Transmembranei206 – 226Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini227 – 229ExtracellularSequence analysis3
Transmembranei230 – 250Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini251 – 325CytoplasmicSequence analysisAdd BLAST75
Transmembranei326 – 346Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini347 – 360ExtracellularSequence analysisAdd BLAST14
Transmembranei361 – 381Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini382 – 383CytoplasmicSequence analysis2
Transmembranei384 – 404Helical; Name=8Sequence analysisAdd BLAST21
Topological domaini405 – 416ExtracellularSequence analysisAdd BLAST12
Transmembranei417 – 437Helical; Name=9Sequence analysisAdd BLAST21
Topological domaini438 – 445CytoplasmicSequence analysis8
Transmembranei446 – 466Helical; Name=10Sequence analysisAdd BLAST21
Topological domaini467 – 491ExtracellularSequence analysisAdd BLAST25
Transmembranei492 – 512Helical; Name=11Sequence analysisAdd BLAST21
Topological domaini513 – 525CytoplasmicSequence analysisAdd BLAST13
Transmembranei526 – 546Helical; Name=12Sequence analysisAdd BLAST21
Topological domaini547 – 559ExtracellularSequence analysisAdd BLAST13
Transmembranei560 – 580Helical; Name=13Sequence analysisAdd BLAST21
Topological domaini581 – 585CytoplasmicSequence analysis5

Keywords - Cellular componenti

Cell membrane, Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 26MitochondrionSequence analysisAdd BLAST26
ChainiPRO_000004575727 – 585Mitochondrial sodium/calcium exchanger proteinAdd BLAST559

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi46N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei258Phosphoserine; by PKABy similarity1

Post-translational modificationi

Phosphorylation at Ser-258 by PKA prevents calcium overload.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ925Q3.
PRIDEiQ925Q3.

PTM databases

PhosphoSitePlusiQ925Q3.

Expressioni

Tissue specificityi

Ubiquitously expressed. Expressed in dental tissues.2 Publications

Gene expression databases

BgeeiENSMUSG00000032754.
ExpressionAtlasiQ925Q3. baseline and differential.
GenevisibleiQ925Q3. MM.

Interactioni

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000064714.

Structurei

3D structure databases

ProteinModelPortaliQ925Q3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2399. Eukaryota.
COG0530. LUCA.
GeneTreeiENSGT00760000119209.
HOGENOMiHOG000113743.
HOVERGENiHBG082009.
InParanoidiQ925Q3.
KOiK13754.
OMAiKMNAYES.
OrthoDBiEOG091G05GE.
PhylomeDBiQ925Q3.
TreeFamiTF323444.

Family and domain databases

InterProiView protein in InterPro
IPR004837. NaCa_Exmemb.
PfamiView protein in Pfam
PF01699. Na_Ca_ex. 2 hits.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q925Q3-1) [UniParc]FASTAAdd to basket
Also known as: L1 Publication, Long1 Publication

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.

« Hide

        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
Length:585
Mass (Da):64,365
Last modified:January 10, 2006 - v2
Checksum:i83B001A9C78B2620
GO
Isoform 2 (identifier: Q925Q3-2) [UniParc]FASTAAdd to basket
Also known as: S1 Publication, Short1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     471-585: DAFSDFTLAR...EFGVIHLKKA → AGARRITGVG...RGVGAILLAS

Show »
Length:552
Mass (Da):60,182
Checksum:i979CDD6786E80281
GO
Isoform 3 (identifier: Q925Q3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     122-140: FCPNLSAISTNLKLSHNVA → PH

Show »
Length:568
Mass (Da):62,588
Checksum:i1C3E0D1C9833FAEB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20I → L in AAK49407 (PubMed:12080145).Curated1
Sequence conflicti228T → A in AAK49407 (PubMed:12080145).Curated1
Sequence conflicti298R → Q in AAK49407 (PubMed:12080145).Curated1
Sequence conflicti381I → L in AAK49407 (PubMed:12080145).Curated1
Sequence conflicti451F → L in AAK49407 (PubMed:12080145).Curated1
Sequence conflicti566I → V in AAK49407 (PubMed:12080145).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016997122 – 140FCPNL…SHNVA → PH in isoform 3. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_016998471 – 585DAFSD…HLKKA → AGARRITGVGAGQCPGPQLD LLPGLRAASVFPAQQGLRPL PPPLLHLFPCCGPAHRVWGD SPEEGVTEAAWPRGVGAILL AS in isoform 2. 1 PublicationAdd BLAST115

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.
CCDSiCCDS39238.1. [Q925Q3-1]
CCDS51633.1. [Q925Q3-2]
CCDS51634.1. [Q925Q3-3]
RefSeqiNP_001171065.1. NM_001177594.1. [Q925Q3-3]
NP_001171066.1. NM_001177595.1. [Q925Q3-2]
NP_573484.2. NM_133221.2. [Q925Q3-1]
UniGeneiMm.291070.

Genome annotation databases

EnsembliENSMUST00000068326; ENSMUSP00000064714; ENSMUSG00000032754. [Q925Q3-1]
ENSMUST00000076051; ENSMUSP00000075428; ENSMUSG00000032754. [Q925Q3-2]
ENSMUST00000111890; ENSMUSP00000107521; ENSMUSG00000032754. [Q925Q3-3]
GeneIDi170756.
KEGGimmu:170756.
UCSCiuc008zhj.2. mouse. [Q925Q3-1]
uc012eco.1. mouse. [Q925Q3-3]
uc012ecp.1. mouse. [Q925Q3-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNCLX_MOUSE
AccessioniPrimary (citable) accession number: Q925Q3
Secondary accession number(s): Q3U067, Q80XM7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: January 10, 2006
Last modified: September 27, 2017
This is version 110 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families