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Q71RS6 (NCKX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/potassium/calcium exchanger 5
Alternative name(s):
Na(+)/K(+)/Ca(2+)-exchange protein 5
Solute carrier family 24 member 5
Gene names
Name:SLC24A5
Synonyms:JSX, NCKX5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length500 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cation exchanger involved in pigmentation, possibly by participating in ion transport in melanosomes. Predominant sodium-Calcium exchanger in melanocytes. Probably transports 1 Ca2+ and 1 K+ to the melanosome in exchange for 4 cytoplasmic Na+. Ref.6 Ref.8

Subcellular location

Golgi apparatustrans-Golgi network membrane; Multi-pass membrane protein. Melanosome. Note: Enriched in late-stage melanosomes. Ref.7 Ref.8

Polymorphism

Genetic variants in SLC24A5 define the skin/hair/eye pigmentation variation locus 4 (SHEP4) [MIM:113750]. 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.

The Ala-111 allele predominates (93 to 100%) in African and East Asian populations. In contrast, the Thr-111 allele is nearly fixed (98.7 to 100%) in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations.

Sequence similarities

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

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q71RS6-1)

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: Q71RS6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     41-101: GNSTQCVISPSSEFPEGFFTRQERRDGGIIIYFLIIVYMFMAISIVCDEYFLPSLEIISES → A

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Chain30 – 500471Sodium/potassium/calcium exchanger 5
PRO_0000045753

Regions

Topological domain30 – 6637Extracellular Potential
Transmembrane67 – 8721Helical; Name=1; Potential
Topological domain88 – 11124Cytoplasmic Potential
Transmembrane112 – 13221Helical; Name=2; Potential
Topological domain133 – 1364Extracellular Potential
Transmembrane137 – 15721Helical; Name=3; Potential
Topological domain158 – 16912Cytoplasmic Potential
Transmembrane170 – 19021Helical; Name=4; Potential
Topological domain191 – 1955Extracellular Potential
Transmembrane196 – 21621Helical; Name=5; Potential
Topological domain217 – 30286Cytoplasmic Potential
Transmembrane303 – 32321Helical; Name=6; Potential
Topological domain324 – 33310Extracellular Potential
Transmembrane334 – 35421Helical; Name=7; Potential
Topological domain355 – 36814Cytoplasmic Potential
Transmembrane369 – 38921Helical; Name=8; Potential
Topological domain390 – 39910Extracellular Potential
Transmembrane400 – 42021Helical; Name=9; Potential
Topological domain421 – 43717Cytoplasmic Potential
Transmembrane438 – 45821Helical; Name=10; Potential
Topological domain459 – 46810Extracellular Potential
Transmembrane469 – 48921Helical; Name=11; Potential
Topological domain490 – 50011Cytoplasmic Potential

Natural variations

Alternative sequence41 – 10161GNSTQ…IISES → A in isoform 2.
VSP_047596
Natural variant1111T → A Associated with SHEP4; greatly reduced exchange activity. Ref.6 Ref.8 Ref.9
Corresponds to variant rs1426654 [ dbSNP | Ensembl ].
VAR_024922

Sequences

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

Last modified July 5, 2004. Version 1.
Checksum: D8E91A017C9651ED

FASTA50054,888
        10         20         30         40         50         60 
MQTKGGQTWA RRALLLGILW ATAHLPLSGT SLPQRLPRAT GNSTQCVISP SSEFPEGFFT 

        70         80         90        100        110        120 
RQERRDGGII IYFLIIVYMF MAISIVCDEY FLPSLEIISE SLGLSQDVAG TTFMAAGSSA 

       130        140        150        160        170        180 
PELVTAFLGV FITKGDIGIS TILGSAIYNL LGICAACGLL SNTVSTLSCW PLFRDCAAYT 

       190        200        210        220        230        240 
ISAAAVLGII YDNQVYWYEG ALLLLIYGLY VLVLCFDIKI NQYIIKKCSP CCACLAKAME 

       250        260        270        280        290        300 
RSEQQPLMGW EDEGQPFIRR QSRTDSGIFY EDSGYSQLSI SLHGLSQVSE DPPSVFNMPE 

       310        320        330        340        350        360 
ADLKRIFWVL SLPIITLLFL TTPDCRKKFW KNYFVITFFM SAIWISAFTY ILVWMVTITG 

       370        380        390        400        410        420 
ETLEIPDTVM GLTLLAAGTS IPDTIASVLV ARKGKGDMAM SNIVGSNVFD MLCLGIPWFI 

       430        440        450        460        470        480 
KTAFINGSAP AEVNSRGLTY ITISLNISII FLFLAVHFNG WKLDRKLGIV CLLSYLGLAT 

       490        500 
LSVLYELGII GNNKIRGCGG 

« Hide

Isoform 2 [UniParc].

Checksum: 33634D113F7A3745
Show »

FASTA44048,016

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel, renal divalent cation transporter (JSX)."
Satoh J., Romero M.F.
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[2]"Cloning and characterization of a K-dependent, Na-Ca2+ exchanger, member 5 (slc24A5) expressed in human retinal pigment epithelium."
Mangini N.J., Kennedy B.G., Canfield V.A., Cheng K.C.
Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Retinal pigment epithelium.
[3]"Molecular cloning of a splice variant of SLC24A5 from human retinal pigment epithelium."
Mangini N.J., Kennedy B.G., Canfield V.A., Cheng K.C.
Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Retinal pigment epithelium.
[4]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
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] (ISOFORM 1).
Tissue: Brain and Mammary gland.
[6]"SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans."
Lamason R.L., Mohideen M.-A.P.K., Mest J.R., Wong A.C., Norton H.L., Aros M.C., Jurynec M.J., Mao X., Humphreville V.R., Humbert J.E., Sinha S., Moore J.L., Jagadeeswaran P., Zhao W., Ning G., Makalowska I., McKeigue P.M., O'Donnell D. expand/collapse author list , Kittles R., Parra E.J., Mangini N.J., Grunwald D.J., Shriver M.D., Canfield V.A., Cheng K.C.
Science 310:1782-1786(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANT ALA-111.
[7]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[8]"SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis."
Ginger R.S., Askew S.E., Ogborne R.M., Wilson S., Ferdinando D., Dadd T., Smith A.M., Kazi S., Szerencsei R.T., Winkfein R.J., Schnetkamp P.P., Green M.R.
J. Biol. Chem. 283:5486-5495(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT ALA-111.
[9]"A genomewide association study of skin pigmentation in a South Asian population."
Stokowski R.P., Pant P.V.K., Dadd T., Fereday A., Hinds D.A., Jarman C., Filsell W., Ginger R.S., Green M.R., van der Ouderaa F.J., Cox D.R.
Am. J. Hum. Genet. 81:1119-1132(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-111, ASSOCIATION WITH SHEP4.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Skin-deep - Issue 74 of September 2006

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF348468 mRNA. Translation: AAQ15116.1.
DQ665306 mRNA. Translation: ABG66958.1.
DQ665307 mRNA. Translation: ABG66959.1.
AC090526 Genomic DNA. No translation available.
BC073944 mRNA. Translation: AAH73944.1.
BC113628 mRNA. Translation: AAI13629.1.
BC113630 mRNA. Translation: AAI13631.1.
BC143950 mRNA. Translation: AAI43951.1.
RefSeqNP_995322.1. NM_205850.2.
XP_005254365.1. XM_005254308.2.
UniGeneHs.710240.

3D structure databases

ProteinModelPortalQ71RS6.
SMRQ71RS6. Positions 363-411.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000341550.

Protein family/group databases

TCDB2.A.19.4.6. the ca(2+):cation antiporter (caca) family.

Polymorphism databases

DMDM74749781.

Proteomic databases

PaxDbQ71RS6.
PRIDEQ71RS6.

Protocols and materials databases

DNASU283652.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341459; ENSP00000341550; ENSG00000188467. [Q71RS6-1]
ENST00000449382; ENSP00000389966; ENSG00000188467. [Q71RS6-2]
GeneID283652.
KEGGhsa:283652.
UCSCuc001zwe.3. human. [Q71RS6-1]

Organism-specific databases

CTD283652.
GeneCardsGC15P048413.
H-InvDBHIX0012216.
HGNCHGNC:20611. SLC24A5.
MIM113750. phenotype.
609802. gene.
neXtProtNX_Q71RS6.
Orphanet370097. Oculocutaneous albinism type 6.
PharmGKBPA134868972.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0530.
HOGENOMHOG000231933.
HOVERGENHBG054881.
InParanoidQ71RS6.
KOK13753.
OMACYILFAT.
OrthoDBEOG776SP8.
PhylomeDBQ71RS6.
TreeFamTF318759.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

BgeeQ71RS6.
CleanExHS_SLC24A5.
GenevestigatorQ71RS6.

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

ChiTaRSSLC24A5. human.
GeneWikiSLC24A5.
GenomeRNAi283652.
NextBio35462293.
PROQ71RS6.
SOURCESearch...

Entry information

Entry nameNCKX5_HUMAN
AccessionPrimary (citable) accession number: Q71RS6
Secondary accession number(s): A5X8Z8 expand/collapse secondary AC list , A5X8Z9, Q14CT4, Q6DKH3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 92 of the entry and version 1 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

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

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 15

Human chromosome 15: entries, gene names and cross-references to MIM