Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q6J4K2 (NCKX6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC8B1
Synonyms:NCKX6, NCLX, SLC24A6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length584 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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+. Ref.1 Ref.6 Ref.7 Ref.8

Enzyme regulation

Strongly inhibited by zinc.

Subcellular location

Mitochondrion inner membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity. Note: Mainly localizes to mitochondrion inner membrane. Ref.6 Ref.8

Tissue specificity

Present in pancreatic beta-cells (at protein level). Ref.8

Sequence similarities

Belongs to the sodium/potassium/calcium exchanger family. SLC24A subfamily.

Sequence caution

The sequence BAB15271.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6J4K2-1)

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.
Isoform 2 (identifier: Q6J4K2-2)

Also known as: S-NCLX;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2626Mitochondrion Potential
Chain27 – 584558Sodium/potassium/calcium exchanger 6, mitochondrial
PRO_0000045756

Regions

Topological domain27 – 9569Extracellular Potential
Transmembrane96 – 11621Helical; Name=1; Potential
Topological domain117 – 14024Cytoplasmic Potential
Transmembrane141 – 16121Helical; Name=2; Potential
Topological domain162 – 1687Extracellular Potential
Transmembrane169 – 18921Helical; Name=3; Potential
Topological domain190 – 20011Cytoplasmic Potential
Transmembrane201 – 22121Helical; Name=4; Potential
Topological domain222 – 2265Extracellular Potential
Transmembrane227 – 24721Helical; Name=5; Potential
Topological domain248 – 32578Cytoplasmic Potential
Transmembrane326 – 34621Helical; Name=6; Potential
Topological domain347 – 36014Extracellular Potential
Transmembrane361 – 38121Helical; Name=7; Potential
Topological domain382 – 3832Cytoplasmic Potential
Transmembrane384 – 40421Helical; Name=8; Potential
Topological domain405 – 41612Extracellular Potential
Transmembrane417 – 43721Helical; Name=9; Potential
Topological domain438 – 4458Cytoplasmic Potential
Transmembrane446 – 46621Helical; Name=10; Potential
Topological domain467 – 48721Extracellular Potential
Transmembrane488 – 50821Helical; Name=11; Potential
Topological domain509 – 52416Cytoplasmic Potential
Transmembrane525 – 54521Helical; Name=12; Potential
Topological domain546 – 55813Extracellular Potential
Transmembrane559 – 57921Helical; Name=13; Potential
Topological domain580 – 5845Cytoplasmic Potential

Amino acid modifications

Glycosylation601N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence176 – 23156Missing in isoform 2.
VSP_016996
Natural variant2221R → C.
Corresponds to variant rs16942745 [ dbSNP | Ensembl ].
VAR_050224
Natural variant3581L → F.
Corresponds to variant rs3764034 [ dbSNP | Ensembl ].
VAR_050225

Experimental info

Sequence conflict571C → R in AAT35807. Ref.1
Sequence conflict1301S → P in AAT35807. Ref.1
Sequence conflict2811N → S in AAT35807. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 10, 2006. Version 2.
Checksum: 6B7008661CC12872

FASTA58464,231
        10         20         30         40         50         60 
MAGRRLNLRW ALSVLCVLLM AETVSGTRGS STGAHISPQF PASGVNQTPV VDCRKVCGLN 

        70         80         90        100        110        120 
VSDRCDFIRT NPDCHSDGGY LDYLEGIFCH FPPSLLPLAV TLYVSWLLYL FLILGVTAAK 

       130        140        150        160        170        180 
FFCPNLSAIS TTLKLSHNVA GVTFLAFGNG APDIFSALVA FSDPHTAGLA LGALFGAGVL 

       190        200        210        220        230        240 
VTTVVAGGIT ILHPFMAASR PFFRDIVFYM VAVFLTFLML FRGRVTLAWA LGYLGLYVFY 

       250        260        270        280        290        300 
VVTVILCTWI YQRQRRGSLF CPMPVTPEIL SDSEEDRVSS NTNSYDYGDE YRPLFFYQET 

       310        320        330        340        350        360 
TAQILVRALN PLDYMKWRRK SAYWKALKVF KLPVEFLLLL TVPVVDPDKD DQNWKRPLNC 

       370        380        390        400        410        420 
LHLVISPLVV VLTLQSGTYG VYEIGGLVPV WVVVVIAGTA LASVTFFATS DSQPPRLHWL 

       430        440        450        460        470        480 
FAFLGFLTSA LWINAAATEV VNILRSLGVV FRLSNTVLGL TLLAWGNSIG DAFSDFTLAR 

       490        500        510        520        530        540 
QGYPRMAFSA CFGGIIFNIL VGVGLGCLLQ ISRSHTEVKL EPDGLLVWVL AGALGLSLVF 

       550        560        570        580 
SLVSVPLQCF QLSRVYGFCL LLFYLNFLVV ALLTEFGVIH LKSM 

« Hide

Isoform 2 (S-NCLX) [UniParc].

Checksum: A1B30D288E0B7B47
Show »

FASTA52858,087

References

« Hide 'large scale' references
[1]"Lithium-calcium exchange is mediated by a distinct potassium-independent sodium-calcium exchanger."
Palty R., Ohana E., Hershfinkel M., Volokita M., Elgazar V., Beharier O., Silverman W.F., Argaman M., Sekler I.
J. Biol. Chem. 279:25234-25240(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION.
[2]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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 1).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 185-584 (ISOFORM 1).
[6]"NCLX is an essential component of mitochondrial Na+/Ca2+ exchange."
Palty R., Silverman W.F., Hershfinkel M., Caporale T., Sensi S.L., Parnis J., Nolte C., Fishman D., Shoshan-Barmatz V., Herrmann S., Khananshvili D., Sekler I.
Proc. Natl. Acad. Sci. U.S.A. 107:436-441(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]"The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic beta-cells."
Tarasov A.I., Semplici F., Ravier M.A., Bellomo E.A., Pullen T.J., Gilon P., Sekler I., Rizzuto R., Rutter G.A.
PLoS ONE 7:E39722-E39722(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"The mitochondrial na(+)/ca(2+) exchanger upregulates glucose dependent ca(2+) signalling linked to insulin secretion."
Nita I.I., Hershfinkel M., Fishman D., Ozeri E., Rutter G.A., Sensi S.L., Khananshvili D., Lewis E.C., Sekler I.
PLoS ONE 7:E46649-E46649(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS31909.1. [Q6J4K2-1]
RefSeqNP_079235.2. NM_024959.2. [Q6J4K2-1]
XP_006719670.1. XM_006719607.1.
XP_006719671.1. XM_006719608.1. [Q6J4K2-1]
UniGeneHs.286194.

3D structure databases

ProteinModelPortalQ6J4K2.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123078. 1 interaction.
IntActQ6J4K2. 1 interaction.
STRING9606.ENSP00000202831.

Protein family/group databases

TCDB2.A.19.4.4. the ca(2+):cation antiporter (caca) family.

PTM databases

PhosphoSiteQ6J4K2.

Polymorphism databases

DMDM85681048.

Proteomic databases

MaxQBQ6J4K2.
PaxDbQ6J4K2.
PRIDEQ6J4K2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000202831; ENSP00000202831; ENSG00000089060. [Q6J4K2-1]
ENST00000546737; ENSP00000450081; ENSG00000089060. [Q6J4K2-2]
ENST00000552014; ENSP00000447091; ENSG00000089060. [Q6J4K2-1]
GeneID80024.
KEGGhsa:80024.
UCSCuc001tvb.3. human. [Q6J4K2-1]

Organism-specific databases

CTD80024.
GeneCardsGC12M113741.
H-InvDBHIX0171623.
HGNCHGNC:26175. SLC8B1.
HPAHPA040668.
MIM609841. gene.
neXtProtNX_Q6J4K2.
PharmGKBPA134954965.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0530.
HOGENOMHOG000113743.
HOVERGENHBG082009.
InParanoidQ6J4K2.
KOK13754.
OMADRVSSNT.
OrthoDBEOG7M0NRK.
PhylomeDBQ6J4K2.
TreeFamTF323444.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ6J4K2.
BgeeQ6J4K2.
CleanExHS_SLC24A6.
GenevestigatorQ6J4K2.

Family and domain databases

InterProIPR004837. NaCa_Exmemb.
[Graphical view]
PfamPF01699. Na_Ca_ex. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi80024.
NextBio70174.
PROQ6J4K2.
SOURCESearch...

Entry information

Entry nameNCKX6_HUMAN
AccessionPrimary (citable) accession number: Q6J4K2
Secondary accession number(s): A6NP50 expand/collapse secondary AC list , Q4KMS9, Q6J4K1, Q9H6I8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: January 10, 2006
Last modified: July 9, 2014
This is version 86 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM