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Protein

Sodium/potassium/calcium exchanger 6, mitochondrial

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, thereby acting as a key regulator of mitochondrion calcium homeostasis. 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. Able to transport Ca2+ in exchange of either Li+ or Na+, explaining how Li+ catalyzes Ca2+ exchange. In contrast to other members of the family its function is independent of K+.1 Publication

GO - Molecular functioni

  • calcium:sodium antiporter activity Source: BHF-UCL
  • calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  • 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 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
  • response to stimulus Source: UniProtKB-KW
  • sodium ion transmembrane transport Source: MGI
Complete GO annotation...

Keywords - Biological processi

Antiport, Calcium transport, Ion transport, Sensory transduction, Sodium transport, Transport

Keywords - Ligandi

Calcium, Lithium, Sodium

Enzyme and pathway databases

ReactomeiR-MMU-425561. Sodium/Calcium exchangers.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/potassium/calcium exchanger 6, mitochondrial
Alternative name(s):
Na(+)/K(+)/Ca(2+)-exchange protein 6
Sodium/calcium exchanger protein, mitochondrial
Solute carrier family 24 member 6
Solute carrier family 8 member B1
Gene namesi
Name:Slc8b1
Synonyms:Nckx6, Nclx, Slc24a6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2180781. Slc8b1.

Subcellular locationi

Isoform 2 :
  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini27 – 9569ExtracellularSequence analysisAdd
BLAST
Transmembranei96 – 11621Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini117 – 14024CytoplasmicSequence analysisAdd
BLAST
Transmembranei141 – 16121Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini162 – 1687ExtracellularSequence analysis
Transmembranei169 – 18921Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini190 – 20516CytoplasmicSequence analysisAdd
BLAST
Transmembranei206 – 22621Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini227 – 2293ExtracellularSequence analysis
Transmembranei230 – 25021Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini251 – 32575CytoplasmicSequence analysisAdd
BLAST
Transmembranei326 – 34621Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini347 – 36014ExtracellularSequence analysisAdd
BLAST
Transmembranei361 – 38121Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini382 – 3832CytoplasmicSequence analysis
Transmembranei384 – 40421Helical; Name=8Sequence analysisAdd
BLAST
Topological domaini405 – 41612ExtracellularSequence analysisAdd
BLAST
Transmembranei417 – 43721Helical; Name=9Sequence analysisAdd
BLAST
Topological domaini438 – 4458CytoplasmicSequence analysis
Transmembranei446 – 46621Helical; Name=10Sequence analysisAdd
BLAST
Topological domaini467 – 49125ExtracellularSequence analysisAdd
BLAST
Transmembranei492 – 51221Helical; Name=11Sequence analysisAdd
BLAST
Topological domaini513 – 52513CytoplasmicSequence analysisAdd
BLAST
Transmembranei526 – 54621Helical; Name=12Sequence analysisAdd
BLAST
Topological domaini547 – 55913ExtracellularSequence analysisAdd
BLAST
Transmembranei560 – 58021Helical; Name=13Sequence analysisAdd
BLAST
Topological domaini581 – 5855CytoplasmicSequence analysis

GO - Cellular componenti

  • cytosol Source: MGI
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of mitochondrial membrane Source: UniProtKB
  • mitochondrial crista Source: BHF-UCL
  • mitochondrial inner membrane Source: MGI
  • mitochondrion Source: BHF-UCL
  • plasma membrane Source: MGI
  • sarcolemma Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion inner membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2626MitochondrionSequence analysisAdd
BLAST
Chaini27 – 585559Sodium/potassium/calcium exchanger 6, mitochondrialPRO_0000045757Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi46 – 461N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ925Q3.
PaxDbiQ925Q3.
PRIDEiQ925Q3.

PTM databases

PhosphoSiteiQ925Q3.

Expressioni

Tissue specificityi

Ubiquitously expressed. Expressed in dental tissues.2 Publications

Gene expression databases

BgeeiQ925Q3.
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.
OMAiANTAMAY.
OrthoDBiEOG7M0NRK.
PhylomeDBiQ925Q3.
TreeFamiTF323444.

Family and domain databases

InterProiIPR004837. NaCa_Exmemb.
[Graphical view]
PfamiPF01699. Na_Ca_ex. 2 hits.
[Graphical view]

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: L, Long

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: S, Short

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti20 – 201I → L in AAK49407 (PubMed:12080145).Curated
Sequence conflicti228 – 2281T → A in AAK49407 (PubMed:12080145).Curated
Sequence conflicti298 – 2981R → Q in AAK49407 (PubMed:12080145).Curated
Sequence conflicti381 – 3811I → L in AAK49407 (PubMed:12080145).Curated
Sequence conflicti451 – 4511F → L in AAK49407 (PubMed:12080145).Curated
Sequence conflicti566 – 5661I → V in AAK49407 (PubMed:12080145).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei122 – 14019FCPNL…SHNVA → PH in isoform 3. 1 PublicationVSP_016997Add
BLAST
Alternative sequencei471 – 585115DAFSD…HLKKA → AGARRITGVGAGQCPGPQLD LLPGLRAASVFPAQQGLRPL PPPLLHLFPCCGPAHRVWGD SPEEGVTEAAWPRGVGAILL AS in isoform 2. 1 PublicationVSP_016998Add
BLAST

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

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.
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.

3D structure databases

ProteinModelPortaliQ925Q3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000064714.

PTM databases

PhosphoSiteiQ925Q3.

Proteomic databases

MaxQBiQ925Q3.
PaxDbiQ925Q3.
PRIDEiQ925Q3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi80024.
MGIiMGI:2180781. Slc8b1.

Phylogenomic databases

eggNOGiKOG2399. Eukaryota.
COG0530. LUCA.
GeneTreeiENSGT00760000119209.
HOGENOMiHOG000113743.
HOVERGENiHBG082009.
InParanoidiQ925Q3.
KOiK13754.
OMAiANTAMAY.
OrthoDBiEOG7M0NRK.
PhylomeDBiQ925Q3.
TreeFamiTF323444.

Enzyme and pathway databases

ReactomeiR-MMU-425561. Sodium/Calcium exchangers.

Miscellaneous databases

NextBioi370346.
PROiQ925Q3.
SOURCEiSearch...

Gene expression databases

BgeeiQ925Q3.
ExpressionAtlasiQ925Q3. baseline and differential.
GenevisibleiQ925Q3. MM.

Family and domain databases

InterProiIPR004837. NaCa_Exmemb.
[Graphical view]
PfamiPF01699. Na_Ca_ex. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Strain: NOD.
    Tissue: Spleen.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: FVB/N.
    Tissue: Liver.
  4. "Molecular cloning of a sixth member of the K+-dependent Na+/Ca2+ exchanger gene family, NCKX6."
    Cai X., Lytton J.
    J. Biol. Chem. 279:5867-5876(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), POSSIBLE FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. Cited for: FUNCTION, SUBCELLULAR LOCATION.
  6. "Expression of the sodium/calcium/potassium exchanger, NCKX4, in ameloblasts."
    Hu P., Lacruz R.S., Smith C.E., Smith S.M., Kurtz I., Paine M.L.
    Cells Tissues Organs 196:501-509(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiNCKX6_MOUSE
AccessioniPrimary (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: March 16, 2016
This is version 98 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Isoform 1 was reported to not have cation exchanger activity. However, such result is unclear (PubMed:12080145).1 Publication

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.