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Protein

Mitochondrial sodium/calcium exchanger protein

Gene

SLC8B1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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:22829870, PubMed:23056385, PubMed:24898248, PubMed:28219928). 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 (By similarity). 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 (PubMed:23056385). 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 (PubMed:28219928). Involved in B-lymphocyte chemotaxis (By similarity). Able to transport Ca2+ in exchange of either Li+ or Na+, explaining how Li+ catalyzes Ca2+ exchange (PubMed:15060069). In contrast to other members of the family its function is independent of K+ (PubMed:15060069).By similarity6 Publications

Enzyme regulationi

Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:24898248). Strongly inhibited by zinc (PubMed:15060069).2 Publications

GO - Molecular functioni

GO - Biological processi

  • glucose homeostasis Source: UniProtKB
  • ion transport Source: Reactome
  • mitochondrial calcium ion homeostasis Source: UniProtKB
  • mitochondrial calcium ion transmembrane transport Source: UniProtKB
  • 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: UniProtKB
  • response to stimulus Source: UniProtKB-KW

Keywordsi

Biological processAntiport, Calcium transport, Ion transport, Sensory transduction, Sodium transport, Transport
LigandCalcium, Lithium, Sodium

Enzyme and pathway databases

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

Protein family/group databases

TCDBi2.A.19.4.4. the ca(2+):cation antiporter (caca) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial sodium/calcium exchanger proteinCurated
Alternative name(s):
Na(+)/K(+)/Ca(2+)-exchange protein 6By similarity
Sodium/calcium exchanger protein, mitochondrial1 Publication
Sodium/potassium/calcium exchanger 6By similarity
Solute carrier family 24 member 6Imported
Solute carrier family 8 member B1Imported
Gene namesi
Name:SLC8B1Imported
Synonyms:NCKX6By similarity, NCLX1 Publication, SLC24A6Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:26175. SLC8B1.

Subcellular locationi

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 – 200CytoplasmicSequence analysisAdd BLAST11
Transmembranei201 – 221Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini222 – 226ExtracellularSequence analysis5
Transmembranei227 – 247Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini248 – 325CytoplasmicSequence analysisAdd BLAST78
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 – 487ExtracellularSequence analysisAdd BLAST21
Transmembranei488 – 508Helical; Name=11Sequence analysisAdd BLAST21
Topological domaini509 – 524CytoplasmicSequence analysisAdd BLAST16
Transmembranei525 – 545Helical; Name=12Sequence analysisAdd BLAST21
Topological domaini546 – 558ExtracellularSequence analysisAdd BLAST13
Transmembranei559 – 579Helical; Name=13Sequence analysisAdd BLAST21
Topological domaini580 – 584CytoplasmicSequence analysis5

GO - Cellular componenti

  • integral component of mitochondrial membrane Source: UniProtKB
  • mitochondrial crista Source: BHF-UCL
  • mitochondrial inner membrane Source: Reactome
  • plasma membrane Source: Reactome
  • sarcolemma Source: Ensembl

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi258S → A: Abolished ability to prevent calcium overload. 1 Publication1
Mutagenesisi258S → D: Phosphomimetic mutant; prevents calcium overload. 1 Publication1

Organism-specific databases

DisGeNETi80024.
OpenTargetsiENSG00000089060.
PharmGKBiPA134954965.

Chemistry databases

ChEMBLiCHEMBL3763001.

Polymorphism and mutation databases

BioMutaiSLC24A6.
DMDMi85681048.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 26MitochondrionSequence analysisAdd BLAST26
ChainiPRO_000004575627 – 584Mitochondrial sodium/calcium exchanger proteinAdd BLAST558

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi60N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei258Phosphoserine; by PKA1 Publication1

Post-translational modificationi

Phosphorylation at Ser-258 by PKA prevents calcium overload.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ6J4K2.
PaxDbiQ6J4K2.
PeptideAtlasiQ6J4K2.
PRIDEiQ6J4K2.

PTM databases

iPTMnetiQ6J4K2.
PhosphoSitePlusiQ6J4K2.

Expressioni

Tissue specificityi

Present in pancreatic beta-cells (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000089060.
CleanExiHS_SLC24A6.
ExpressionAtlasiQ6J4K2. baseline and differential.
GenevisibleiQ6J4K2. HS.

Organism-specific databases

HPAiHPA040668.

Interactioni

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

IntActiQ6J4K2. 1 interactor.
STRINGi9606.ENSP00000202831.

Structurei

3D structure databases

ProteinModelPortaliQ6J4K2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2399. Eukaryota.
COG0530. LUCA.
GeneTreeiENSGT00760000119209.
HOGENOMiHOG000113743.
HOVERGENiHBG082009.
InParanoidiQ6J4K2.
KOiK13754.
OMAiAHISPQF.
OrthoDBiEOG091G05GE.
PhylomeDBiQ6J4K2.
TreeFamiTF323444.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6J4K2-1) [UniParc]FASTAAdd to basket

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
MAGRRLNLRW ALSVLCVLLM AETVSGTRGS STGAHISPQF PASGVNQTPV
60 70 80 90 100
VDCRKVCGLN VSDRCDFIRT NPDCHSDGGY LDYLEGIFCH FPPSLLPLAV
110 120 130 140 150
TLYVSWLLYL FLILGVTAAK FFCPNLSAIS TTLKLSHNVA GVTFLAFGNG
160 170 180 190 200
APDIFSALVA FSDPHTAGLA LGALFGAGVL VTTVVAGGIT ILHPFMAASR
210 220 230 240 250
PFFRDIVFYM VAVFLTFLML FRGRVTLAWA LGYLGLYVFY VVTVILCTWI
260 270 280 290 300
YQRQRRGSLF CPMPVTPEIL SDSEEDRVSS NTNSYDYGDE YRPLFFYQET
310 320 330 340 350
TAQILVRALN PLDYMKWRRK SAYWKALKVF KLPVEFLLLL TVPVVDPDKD
360 370 380 390 400
DQNWKRPLNC LHLVISPLVV VLTLQSGTYG VYEIGGLVPV WVVVVIAGTA
410 420 430 440 450
LASVTFFATS DSQPPRLHWL FAFLGFLTSA LWINAAATEV VNILRSLGVV
460 470 480 490 500
FRLSNTVLGL TLLAWGNSIG DAFSDFTLAR QGYPRMAFSA CFGGIIFNIL
510 520 530 540 550
VGVGLGCLLQ ISRSHTEVKL EPDGLLVWVL AGALGLSLVF SLVSVPLQCF
560 570 580
QLSRVYGFCL LLFYLNFLVV ALLTEFGVIH LKSM
Length:584
Mass (Da):64,231
Last modified:January 10, 2006 - v2
Checksum:i6B7008661CC12872
GO
Isoform 2 (identifier: Q6J4K2-2) [UniParc]FASTAAdd to basket
Also known as: S-NCLX1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     176-231: Missing.

Show »
Length:528
Mass (Da):58,087
Checksum:iA1B30D288E0B7B47
GO

Sequence cautioni

The sequence BAB15271 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57C → R in AAT35807 (PubMed:15060069).Curated1
Sequence conflicti130S → P in AAT35807 (PubMed:15060069).Curated1
Sequence conflicti281N → S in AAT35807 (PubMed:15060069).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050224222R → C. Corresponds to variant dbSNP:rs16942745Ensembl.1
Natural variantiVAR_050225358L → F. Corresponds to variant dbSNP:rs3764034Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016996176 – 231Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY601759 mRNA. Translation: AAT35807.1.
AY601760 mRNA. Translation: AAT35808.1.
AC010178 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW98050.1.
BC098360 mRNA. Translation: AAH98360.1.
AK025886 mRNA. Translation: BAB15271.1. Different initiation.
CCDSiCCDS31909.1. [Q6J4K2-1]
CCDS81744.1. [Q6J4K2-2]
RefSeqiNP_001317395.1. NM_001330466.1. [Q6J4K2-2]
NP_079235.2. NM_024959.3. [Q6J4K2-1]
XP_006719670.1. XM_006719607.2.
XP_011537051.1. XM_011538749.2. [Q6J4K2-1]
XP_011537054.1. XM_011538752.2.
UniGeneiHs.286194.

Genome annotation databases

EnsembliENST00000202831; ENSP00000202831; ENSG00000089060. [Q6J4K2-1]
ENST00000546737; ENSP00000450081; ENSG00000089060. [Q6J4K2-2]
ENST00000552014; ENSP00000447091; ENSG00000089060. [Q6J4K2-1]
GeneIDi80024.
KEGGihsa:80024.
UCSCiuc001tvc.4. human. [Q6J4K2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNCLX_HUMAN
AccessioniPrimary (citable) accession number: Q6J4K2
Secondary accession number(s): A6NP50
, Q4KMS9, Q6J4K1, Q9H6I8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: January 10, 2006
Last modified: August 30, 2017
This is version 113 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families