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Q8NFF2 (NCKX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. 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 4
Alternative name(s):
Na(+)/K(+)/Ca(2+)-exchange protein 4
Solute carrier family 24 member 4
Gene names
Name:SLC24A4
Synonyms:NCKX4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length622 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transports 1 Ca2+ and 1 K+ in exchange for 4 Na+. Controls the rapid response termination and proper regulation of adaptation in olfactory sensory neurons (OSNs) which subsequently influences how odor information is encoded and perceived. May play a role in calcium transport during amelogenesis By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed abundantly in all regions of the brain, aorta, lung and thymus. Expressed at lower levels in the stomach and intestine.

Polymorphism

Genetic variants in SLC24A4 define the skin/hair/eye pigmentation variation locus 6 (SHEP6) [MIM:210750]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.

Involvement in disease

SLC24A4 mutations may be a cause of autosomal recessive hypomineralized amelogenesis imperfecta (AI), a defect of enamel formation characterized by variable degrees of incomplete mineralization of the enamel matrix, typically with a near-normal enamel matrix volume prior to posteruptive changes and premature failure. Ref.8

Sequence similarities

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

Caution

It is uncertain whether Met-1 or Met-18 is the initiator.

Sequence caution

The sequence AAH69653.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAM76070.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAM76071.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAC04715.1 differs from that shown. Reason: Probable cloning artifact.

The sequence CAD38903.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8NFF2-1)

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: Q8NFF2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-64: Missing.
Isoform 3 (identifier: Q8NFF2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     275-293: Missing.
Isoform 4 (identifier: Q8NFF2-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-109: Missing.
     172-210: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3838 Potential
Chain39 – 622584Sodium/potassium/calcium exchanger 4
PRO_0000019373

Regions

Topological domain39 – 9759Extracellular Potential
Transmembrane98 – 11821Helical; Potential
Topological domain119 – 17254Cytoplasmic Potential
Transmembrane173 – 19321Helical; Potential
Topological domain194 – 2007Extracellular Potential
Transmembrane201 – 22121Helical; Potential
Topological domain222 – 2243Cytoplasmic Potential
Transmembrane225 – 24521Helical; Potential
Topological domain246 – 424179Extracellular Potential
Transmembrane425 – 44521Helical; Potential
Topological domain446 – 45712Cytoplasmic Potential
Transmembrane458 – 47821Helical; Potential
Topological domain4791Extracellular Potential
Transmembrane480 – 50021Helical; Potential
Topological domain501 – 52626Cytoplasmic Potential
Transmembrane527 – 54721Helical; Potential
Topological domain548 – 55710Extracellular Potential
Transmembrane558 – 57821Helical; Potential
Topological domain579 – 5868Cytoplasmic Potential
Transmembrane587 – 60721Helical; Potential
Topological domain608 – 62215Extracellular Potential
Repeat139 – 17941Alpha-1
Repeat495 – 52632Alpha-2
Compositional bias395 – 40612Poly-Pro

Amino acid modifications

Glycosylation691N-linked (GlcNAc...) Potential
Glycosylation761N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 109109Missing in isoform 4.
VSP_008370
Alternative sequence1 – 6464Missing in isoform 2.
VSP_008369
Alternative sequence172 – 21039Missing in isoform 4.
VSP_008371
Alternative sequence275 – 29319Missing in isoform 3.
VSP_008372
Natural variant4991S → C Probable disease-associated mutation found in autosomal recessive hypomineralized amelogenesis imperfecta. Ref.8
VAR_070183
Natural variant6131V → I.
Corresponds to variant rs4900130 [ dbSNP | Ensembl ].
VAR_042664

Experimental info

Sequence conflict4441C → S in BAC04715. Ref.2
Sequence conflict5601Y → H in BAG58108. Ref.2

Sequences

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

Last modified July 27, 2011. Version 2.
Checksum: 00D69370E55EE388

FASTA62269,042
        10         20         30         40         50         60 
MALRGTLRPL KVRRRREMLP QQVGFVCAVL ALVCCASGLF GSLGHKTASA SKRVLPDTWR 

        70         80         90        100        110        120 
NRKLMAPVNG TQTAKNCTDP AIHEFPTDLF SNKERQHGAV LLHILGALYM FYALAIVCDD 

       130        140        150        160        170        180 
FFVPSLEKIC ERLHLSEDVA GATFMAAGSS TPELFASVIG VFITHGDVGV GTIVGSAVFN 

       190        200        210        220        230        240 
ILCIIGVCGL FAGQVVRLTW WAVCRDSVYY TISVIVLIVF IYDEQIVWWE GLVLIILYVF 

       250        260        270        280        290        300 
YILIMKYNVK MQAFFTVKQK SIANGNPVNS ELEAGNDFYD GSYDDPSVPL LGQVKEKPQY 

       310        320        330        340        350        360 
GKNPVVMVDE IMSSSPPKFT FPEAGLRIMI TNKFGPRTRL RMASRIIINE RQRLINSANG 

       370        380        390        400        410        420 
VSSKPLQNGR HENIENGNVP VENPEDPQQN QEQQPPPQPP PPEPEPVEAD FLSPFSVPEA 

       430        440        450        460        470        480 
RGDKVKWVFT WPLIFLLCVT IPNCSKPRWE KFFMVTFITA TLWIAVFSYI MVWLVTIIGY 

       490        500        510        520        530        540 
TLGIPDVIMG ITFLAAGTSV PDCMASLIVA RQGLGDMAVS NTIGSNVFDI LVGLGVPWGL 

       550        560        570        580        590        600 
QTMVVNYGST VKINSRGLVY SVVLLLGSVA LTVLGIHLNK WRLDRKLGVY VLVLYAIFLC 

       610        620 
FSIMIEFNVF TFVNLPMCRE DD 

« Hide

Isoform 2 [UniParc].

Checksum: 3DC0E1DFBC5D7828
Show »

FASTA55861,938
Isoform 3 [UniParc].

Checksum: C8A7D3637BF861F8
Show »

FASTA60367,001
Isoform 4 [UniParc].

Checksum: 5C9395536A220F7A
Show »

FASTA47452,760

References

« Hide 'large scale' references
[1]"Molecular cloning of a fourth member of the potassium-dependent sodium-calcium exchanger gene family, NCKX4."
Li X.-F., Kraev A.S., Lytton J.
J. Biol. Chem. 277:48410-48417(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF 10-622 (ISOFORMS 1 AND 3).
[2]"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] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-474 (ISOFORM 4).
Tissue: Brain.
[3]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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].
[5]"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] OF 10-622 (ISOFORM 1).
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 294-622 (ISOFORM 1).
Tissue: Testis.
[7]"Genetic determinants of hair, eye and skin pigmentation in Europeans."
Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G., Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B., Thorisdottir K., Ragnarsson R., Benediktsdottir K.R. expand/collapse author list , Aben K.K., Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K.
Nat. Genet. 39:1443-1452(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SHEP6.
[8]"Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta."
Parry D.A., Poulter J.A., Logan C.V., Brookes S.J., Jafri H., Ferguson C.H., Anwari B.M., Rashid Y., Zhao H., Johnson C.A., Inglehearn C.F., Mighell A.J.
Am. J. Hum. Genet. 92:307-312(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN AI, VARIANT CYS-499.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF520704 mRNA. Translation: AAM76070.1. Different initiation.
AF520705 mRNA. Translation: AAM76071.1. Different initiation.
AF520706 mRNA. Translation: AAM76072.1.
AK096171 mRNA. Translation: BAC04715.1. Sequence problems.
AK295059 mRNA. Translation: BAG58108.1.
AL118559 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81485.1.
BC069653 mRNA. Translation: AAH69653.1. Different initiation.
AL834225 mRNA. Translation: CAD38903.1. Different initiation.
CCDSCCDS45155.2. [Q8NFF2-3]
CCDS45156.1. [Q8NFF2-2]
CCDS9903.2. [Q8NFF2-1]
RefSeqNP_705932.2. NM_153646.3. [Q8NFF2-1]
NP_705933.2. NM_153647.3. [Q8NFF2-3]
NP_705934.1. NM_153648.3. [Q8NFF2-2]
XP_005267398.1. XM_005267341.1. [Q8NFF2-1]
UniGeneHs.385530.

3D structure databases

ProteinModelPortalQ8NFF2.
SMRQ8NFF2. Positions 120-242, 452-536.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000298877.

Protein family/group databases

TCDB2.A.19.4.5. the ca(2+):cation antiporter (caca) family.

Polymorphism databases

DMDM341941166.

Proteomic databases

PaxDbQ8NFF2.
PRIDEQ8NFF2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298877; ENSP00000298877; ENSG00000140090.
ENST00000351924; ENSP00000337789; ENSG00000140090.
ENST00000393265; ENSP00000376948; ENSG00000140090. [Q8NFF2-2]
ENST00000531433; ENSP00000433302; ENSG00000140090. [Q8NFF2-3]
ENST00000532405; ENSP00000431840; ENSG00000140090. [Q8NFF2-1]
GeneID123041.
KEGGhsa:123041.
UCSCuc001yai.3. human. [Q8NFF2-1]
uc010twm.2. human. [Q8NFF2-3]

Organism-specific databases

CTD123041.
GeneCardsGC14P092788.
HGNCHGNC:10978. SLC24A4.
MIM210750. phenotype.
609840. gene.
neXtProtNX_Q8NFF2.
Orphanet100032. Hypocalcified amelogenesis imperfecta.
PharmGKBPA35854.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0530.
HOVERGENHBG054881.
InParanoidQ8NFF2.
KOK13752.
OMAKLMAPVN.
OrthoDBEOG776SP8.
PhylomeDBQ8NFF2.
TreeFamTF318759.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ8NFF2.
BgeeQ8NFF2.
CleanExHS_SLC24A4.
GenevestigatorQ8NFF2.

Family and domain databases

InterProIPR004481. K/Na/Ca-exchanger.
IPR004837. NaCa_Exmemb.
[Graphical view]
PANTHERPTHR10846. PTHR10846. 1 hit.
PfamPF01699. Na_Ca_ex. 2 hits.
[Graphical view]
TIGRFAMsTIGR00367. TIGR00367. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi123041.
NextBio81061.
PROQ8NFF2.
SOURCESearch...

Entry information

Entry nameNCKX4_HUMAN
AccessionPrimary (citable) accession number: Q8NFF2
Secondary accession number(s): B4DHE7 expand/collapse secondary AC list , B9ZVY2, Q8N8U6, Q8NCX1, Q8NFF0, Q8NFF1
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 111 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 14

Human chromosome 14: entries, gene names and cross-references to MIM