UniProtKB - Q6J4K2 (NCLX_HUMAN)
Protein
Mitochondrial sodium/calcium exchanger protein
Gene
SLC8B1
Organism
Homo sapiens (Human)
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: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
Activity regulationi
Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:24898248). Strongly inhibited by zinc (PubMed:15060069).2 Publications
GO - Molecular functioni
- calcium:cation antiporter activity Source: Reactome
- calcium:sodium antiporter activity Source: UniProtKB
- calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential Source: UniProtKB
- cation transmembrane transporter activity Source: GO_Central
- protein homodimerization activity Source: BHF-UCL
GO - Biological processi
- calcium export from the mitochondrion Source: UniProtKB
- cation transport Source: GO_Central
- cellular calcium ion homeostasis Source: GO_Central
- glucose homeostasis Source: UniProtKB
- ion transport Source: Reactome
- mitochondrial calcium ion homeostasis Source: UniProtKB
- mitochondrial calcium ion transmembrane transport 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 process | Antiport, Calcium transport, Ion transport, Sensory transduction, Sodium transport, Transport |
Ligand | Calcium, Lithium, Sodium |
Enzyme and pathway databases
PathwayCommonsi | Q6J4K2 |
Reactomei | R-HSA-425561, Sodium/Calcium exchangers R-HSA-8949215, Mitochondrial calcium ion transport |
Protein family/group databases
TCDBi | 2.A.19.4.4, the ca(2+):cation antiporter (caca) family |
Names & Taxonomyi
Protein namesi | Recommended name: Mitochondrial sodium/calcium exchanger proteinCuratedAlternative 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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:26175, SLC8B1 |
MIMi | 609841, gene |
neXtProti | NX_Q6J4K2 |
VEuPathDBi | HostDB:ENSG00000089060.11 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane 2 Publications; Multi-pass membrane protein 2 Publications
Mitochondrion
- integral component of mitochondrial membrane Source: UniProtKB
- mitochondrial crista Source: BHF-UCL
- mitochondrial inner membrane Source: Reactome
Plasma Membrane
- plasma membrane Source: Reactome
- sarcolemma Source: Ensembl
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 – 200 | CytoplasmicSequence analysisAdd BLAST | 11 | |
Transmembranei | 201 – 221 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 222 – 226 | ExtracellularSequence analysis | 5 | |
Transmembranei | 227 – 247 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 248 – 325 | CytoplasmicSequence analysisAdd BLAST | 78 | |
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 – 487 | ExtracellularSequence analysisAdd BLAST | 21 | |
Transmembranei | 488 – 508 | Helical; Name=11Sequence analysisAdd BLAST | 21 | |
Topological domaini | 509 – 524 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 525 – 545 | Helical; Name=12Sequence analysisAdd BLAST | 21 | |
Topological domaini | 546 – 558 | ExtracellularSequence analysisAdd BLAST | 13 | |
Transmembranei | 559 – 579 | Helical; Name=13Sequence analysisAdd BLAST | 21 | |
Topological domaini | 580 – 584 | CytoplasmicSequence analysis | 5 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 258 | S → A: Abolished ability to prevent calcium overload. 1 Publication | 1 | |
Mutagenesisi | 258 | S → D: Phosphomimetic mutant; prevents calcium overload. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 80024 |
OpenTargetsi | ENSG00000089060 |
PharmGKBi | PA134954965 |
Miscellaneous databases
Pharosi | Q6J4K2, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3763001 |
Genetic variation databases
BioMutai | SLC8B1 |
DMDMi | 85681048 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 26 | MitochondrionSequence analysisAdd BLAST | 26 | |
ChainiPRO_0000045756 | 27 – 584 | Mitochondrial sodium/calcium exchanger proteinAdd BLAST | 558 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 60 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 258 | Phosphoserine; by PKA1 Publication | 1 |
Post-translational modificationi
Phosphorylation at Ser-258 by PKA prevents calcium overload.1 Publication
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | Q6J4K2 |
MassIVEi | Q6J4K2 |
MaxQBi | Q6J4K2 |
PaxDbi | Q6J4K2 |
PeptideAtlasi | Q6J4K2 |
PRIDEi | Q6J4K2 |
ProteomicsDBi | 66508 [Q6J4K2-1] 66509 [Q6J4K2-2] |
PTM databases
GlyGeni | Q6J4K2, 1 site |
iPTMneti | Q6J4K2 |
PhosphoSitePlusi | Q6J4K2 |
Expressioni
Tissue specificityi
Present in pancreatic beta-cells (at protein level).1 Publication
Gene expression databases
Bgeei | ENSG00000089060, Expressed in right adrenal gland and 199 other tissues |
ExpressionAtlasi | Q6J4K2, baseline and differential |
Genevisiblei | Q6J4K2, HS |
Organism-specific databases
HPAi | ENSG00000089060, Low tissue specificity |
Interactioni
GO - Molecular functioni
- protein homodimerization activity Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 123078, 2 interactors |
IntActi | Q6J4K2, 1 interactor |
STRINGi | 9606.ENSP00000447091 |
Chemistry databases
BindingDBi | Q6J4K2 |
Miscellaneous databases
RNActi | Q6J4K2, 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 | Q6J4K2 |
OMAi | WIMNIAN |
OrthoDBi | 478735at2759 |
PhylomeDBi | Q6J4K2 |
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 (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q6J4K2-1) [UniParc]FASTAAdd to basket
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
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
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8VR99 | F8VR99_HUMAN | Mitochondrial sodium/calcium exchan... | SLC8B1 | 231 | Annotation score: | ||
F8VW44 | F8VW44_HUMAN | Mitochondrial sodium/calcium exchan... | SLC8B1 | 143 | Annotation score: | ||
H0YI75 | H0YI75_HUMAN | Mitochondrial sodium/calcium exchan... | SLC8B1 | 404 | Annotation score: | ||
F8VWW9 | F8VWW9_HUMAN | Mitochondrial sodium/calcium exchan... | SLC8B1 | 131 | Annotation score: | ||
A0A0B4J252 | A0A0B4J252_HUMAN | Mitochondrial sodium/calcium exchan... | SLC8B1 | 99 | Annotation score: | ||
F8W134 | F8W134_HUMAN | Mitochondrial sodium/calcium exchan... | SLC8B1 | 53 | Annotation score: | ||
F8VTU4 | F8VTU4_HUMAN | Mitochondrial sodium/calcium exchan... | SLC8B1 | 103 | Annotation score: |
Sequence cautioni
The sequence BAB15271 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 57 | C → R in AAT35807 (PubMed:15060069).Curated | 1 | |
Sequence conflicti | 130 | S → P in AAT35807 (PubMed:15060069).Curated | 1 | |
Sequence conflicti | 281 | N → S in AAT35807 (PubMed:15060069).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_050224 | 222 | R → C. Corresponds to variant dbSNP:rs16942745Ensembl. | 1 | |
Natural variantiVAR_050225 | 358 | L → F. Corresponds to variant dbSNP:rs3764034Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016996 | 176 – 231 | Missing in isoform 2. 1 PublicationAdd BLAST | 56 |
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. |
CCDSi | CCDS31909.1 [Q6J4K2-1] CCDS81744.1 [Q6J4K2-2] |
RefSeqi | NP_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 XP_011537054.1, XM_011538752.2 |
Genome annotation databases
Ensembli | ENST00000202831; ENSP00000202831; ENSG00000089060 [Q6J4K2-1] ENST00000546737; ENSP00000450081; ENSG00000089060 [Q6J4K2-2] ENST00000552014; ENSP00000447091; ENSG00000089060 [Q6J4K2-1] |
GeneIDi | 80024 |
KEGGi | hsa:80024 |
UCSCi | uc001tvc.4, human [Q6J4K2-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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. |
CCDSi | CCDS31909.1 [Q6J4K2-1] CCDS81744.1 [Q6J4K2-2] |
RefSeqi | NP_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 XP_011537054.1, XM_011538752.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 123078, 2 interactors |
IntActi | Q6J4K2, 1 interactor |
STRINGi | 9606.ENSP00000447091 |
Chemistry databases
BindingDBi | Q6J4K2 |
ChEMBLi | CHEMBL3763001 |
Protein family/group databases
TCDBi | 2.A.19.4.4, the ca(2+):cation antiporter (caca) family |
PTM databases
GlyGeni | Q6J4K2, 1 site |
iPTMneti | Q6J4K2 |
PhosphoSitePlusi | Q6J4K2 |
Genetic variation databases
BioMutai | SLC8B1 |
DMDMi | 85681048 |
Proteomic databases
jPOSTi | Q6J4K2 |
MassIVEi | Q6J4K2 |
MaxQBi | Q6J4K2 |
PaxDbi | Q6J4K2 |
PeptideAtlasi | Q6J4K2 |
PRIDEi | Q6J4K2 |
ProteomicsDBi | 66508 [Q6J4K2-1] 66509 [Q6J4K2-2] |
Protocols and materials databases
Antibodypediai | 31257, 85 antibodies |
Genome annotation databases
Ensembli | ENST00000202831; ENSP00000202831; ENSG00000089060 [Q6J4K2-1] ENST00000546737; ENSP00000450081; ENSG00000089060 [Q6J4K2-2] ENST00000552014; ENSP00000447091; ENSG00000089060 [Q6J4K2-1] |
GeneIDi | 80024 |
KEGGi | hsa:80024 |
UCSCi | uc001tvc.4, human [Q6J4K2-1] |
Organism-specific databases
CTDi | 80024 |
DisGeNETi | 80024 |
GeneCardsi | SLC8B1 |
HGNCi | HGNC:26175, SLC8B1 |
HPAi | ENSG00000089060, Low tissue specificity |
MIMi | 609841, gene |
neXtProti | NX_Q6J4K2 |
OpenTargetsi | ENSG00000089060 |
PharmGKBi | PA134954965 |
VEuPathDBi | HostDB:ENSG00000089060.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2399, Eukaryota |
GeneTreei | ENSGT00940000157433 |
HOGENOMi | CLU_004979_3_2_1 |
InParanoidi | Q6J4K2 |
OMAi | WIMNIAN |
OrthoDBi | 478735at2759 |
PhylomeDBi | Q6J4K2 |
TreeFami | TF323444 |
Enzyme and pathway databases
PathwayCommonsi | Q6J4K2 |
Reactomei | R-HSA-425561, Sodium/Calcium exchangers R-HSA-8949215, Mitochondrial calcium ion transport |
Miscellaneous databases
BioGRID-ORCSi | 80024, 8 hits in 860 CRISPR screens |
ChiTaRSi | SLC8B1, human |
GenomeRNAii | 80024 |
Pharosi | Q6J4K2, Tbio |
PROi | PR:Q6J4K2 |
RNActi | Q6J4K2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000089060, Expressed in right adrenal gland and 199 other tissues |
ExpressionAtlasi | Q6J4K2, baseline and differential |
Genevisiblei | Q6J4K2, HS |
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_HUMAN | |
Accessioni | Q6J4K2Primary (citable) accession number: Q6J4K2 Secondary accession number(s): A6NP50 Q9H6I8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 10, 2006 |
Last sequence update: | January 10, 2006 | |
Last modified: | February 10, 2021 | |
This is version 137 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human entries with genetic variants
List of human entries with genetic variants