Q6J4K2 (NCKX6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	SLC24A6
Synonyms:	NCKX6, NCLX

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	584 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Antiport Calcium transport Ion transport Sensory transduction Sodium transport Transport
Cellular component	Cell membrane Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide Transmembrane Transmembrane helix
Ligand	Calcium Lithium Sodium
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glucose homeostasis Inferred from direct assay Ref.8. Source: UniProtKB mitochondrial calcium ion transport Inferred from direct assay Ref.8. Source: UniProtKB regulation of insulin secretion Inferred from direct assay Ref.8. Source: UniProtKB response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to mitochondrial membrane Inferred from direct assay Ref.8. Source: UniProtKB mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Traceable author statement. Source: Reactome sarcolemma Inferred from electronic annotation. Source: Compara
Molecular_function	calcium:sodium antiporter activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 26	26	Mitochondrion Potential
	Chain	27 – 584	558	Sodium/potassium/calcium exchanger 6, mitochondrial		PRO_0000045756
Regions
	Topological domain	27 – 95	69	Extracellular Potential
	Transmembrane	96 – 116	21	Helical; Name=1; Potential
	Topological domain	117 – 140	24	Cytoplasmic Potential
	Transmembrane	141 – 161	21	Helical; Name=2; Potential
	Topological domain	162 – 168	7	Extracellular Potential
	Transmembrane	169 – 189	21	Helical; Name=3; Potential
	Topological domain	190 – 200	11	Cytoplasmic Potential
	Transmembrane	201 – 221	21	Helical; Name=4; Potential
	Topological domain	222 – 226	5	Extracellular Potential
	Transmembrane	227 – 247	21	Helical; Name=5; Potential
	Topological domain	248 – 325	78	Cytoplasmic Potential
	Transmembrane	326 – 346	21	Helical; Name=6; Potential
	Topological domain	347 – 360	14	Extracellular Potential
	Transmembrane	361 – 381	21	Helical; Name=7; Potential
	Topological domain	382 – 383	2	Cytoplasmic Potential
	Transmembrane	384 – 404	21	Helical; Name=8; Potential
	Topological domain	405 – 416	12	Extracellular Potential
	Transmembrane	417 – 437	21	Helical; Name=9; Potential
	Topological domain	438 – 445	8	Cytoplasmic Potential
	Transmembrane	446 – 466	21	Helical; Name=10; Potential
	Topological domain	467 – 487	21	Extracellular Potential
	Transmembrane	488 – 508	21	Helical; Name=11; Potential
	Topological domain	509 – 524	16	Cytoplasmic Potential
	Transmembrane	525 – 545	21	Helical; Name=12; Potential
	Topological domain	546 – 558	13	Extracellular Potential
	Transmembrane	559 – 579	21	Helical; Name=13; Potential
	Topological domain	580 – 584	5	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	60	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	176 – 231	56	Missing in isoform 2.		VSP_016996
	Natural variant	222	1	R → C. Corresponds to variant rs16942745 [ dbSNP | Ensembl ].		VAR_050224
	Natural variant	358	1	L → F. Corresponds to variant rs3764034 [ dbSNP | Ensembl ].		VAR_050225
Experimental info
	Sequence conflict	57	1	C → R in AAT35807. Ref.1
	Sequence conflict	130	1	S → P in AAT35807. Ref.1
	Sequence conflict	281	1	N → S in AAT35807. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 10, 2006. Version 2. Checksum: 6B7008661CC12872	FASTA	584	64,231
	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
	Isoform 2 (S-NCLX) [UniParc]. Checksum: A1B30D288E0B7B47	FASTA	528	58,087
	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 LGALFGYLGL 190 200 210 220 230 240 YVFYVVTVIL CTWIYQRQRR GSLFCPMPVT PEILSDSEED RVSSNTNSYD YGDEYRPLFF 250 260 270 280 290 300 YQETTAQILV RALNPLDYMK WRRKSAYWKA LKVFKLPVEF LLLLTVPVVD PDKDDQNWKR 310 320 330 340 350 360 PLNCLHLVIS PLVVVLTLQS GTYGVYEIGG LVPVWVVVVI AGTALASVTF FATSDSQPPR 370 380 390 400 410 420 LHWLFAFLGF LTSALWINAA ATEVVNILRS LGVVFRLSNT VLGLTLLAWG NSIGDAFSDF 430 440 450 460 470 480 TLARQGYPRM AFSACFGGII FNILVGVGLG CLLQISRSHT EVKLEPDGLL VWVLAGALGL 490 500 510 520 SLVFSLVSVP LQCFQLSRVY GFCLLLFYLN FLVVALLTEF GVIHLKSM

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00017232. IPI00452007.
RefSeq	NP_079235.2. NM_024959.2.
UniGene	Hs.286194.
3D structure databases
ProteinModelPortal	Q6J4K2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6J4K2. 1 interaction.
STRING	9606.ENSP00000202831.
Protein family/group databases
TCDB	2.A.19.4.4. Ca2+:cation antiporter (CaCA) family.
PTM databases
PhosphoSite	Q6J4K2.
Polymorphism databases
DMDM	85681048.
Proteomic databases
PaxDb	Q6J4K2.
PRIDE	Q6J4K2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000202831; ENSP00000202831; ENSG00000089060. ENST00000546737; ENSP00000450081; ENSG00000089060. ENST00000552014; ENSP00000447091; ENSG00000089060.
GeneID	80024.
KEGG	hsa:80024.
UCSC	uc001tvb.3. human.
Organism-specific databases
CTD	80024.
GeneCards	GC12M113736.
H-InvDB	HIX0171623.
HGNC	HGNC:26175. SLC24A6.
HPA	HPA040668.
MIM	609841. gene.
neXtProt	NX_Q6J4K2.
PharmGKB	PA134954965.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0530.
HOGENOM	HOG000113743.
HOVERGEN	HBG082009.
InParanoid	Q6J4K2.
KO	K13754.
OMA	DRVSSNT.
OrthoDB	EOG49W2FP.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q6J4K2.
Bgee	Q6J4K2.
CleanEx	HS_SLC24A6.
Genevestigator	Q6J4K2.
GermOnline	ENSG00000089060. Homo sapiens.
Family and domain databases
InterPro	IPR004837. NaCa_Exmemb. [Graphical view]
Pfam	PF01699. Na_Ca_ex. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	80024.
NextBio	70174.
SOURCE	Search...

Entry information

Entry name

NCKX6_HUMAN

Accession

Primary (citable) accession number: Q6J4K2
Secondary accession number(s): A6NP50 , Q4KMS9, Q6J4K1, Q9H6I8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	January 10, 2006
Last modified:	April 3, 2013
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.