NCKX5_HUMAN
ID NCKX5_HUMAN Reviewed; 500 AA.
AC Q71RS6; A5X8Z8; A5X8Z9; Q14CT4; Q6DKH3;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Sodium/potassium/calcium exchanger 5;
DE AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 5;
DE AltName: Full=Solute carrier family 24 member 5;
DE Flags: Precursor;
GN Name=SLC24A5 {ECO:0000303|PubMed:16357253, ECO:0000312|HGNC:HGNC:20611};
GN Synonyms=JSX {ECO:0000303|Ref.1}, NCKX5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Satoh J., Romero M.F.;
RT "Cloning and characterization of a novel, renal divalent cation transporter
RT (JSX).";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Retinal pigment epithelium;
RA Mangini N.J., Kennedy B.G., Canfield V.A., Cheng K.C.;
RT "Cloning and characterization of a K-dependent, Na-Ca2+ exchanger, member 5
RT (slc24A5) expressed in human retinal pigment epithelium.";
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Retinal pigment epithelium;
RA Mangini N.J., Kennedy B.G., Canfield V.A., Cheng K.C.;
RT "Molecular cloning of a splice variant of SLC24A5 from human retinal
RT pigment epithelium.";
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, AND VARIANT ALA-111.
RX PubMed=16357253; DOI=10.1126/science.1116238;
RA Lamason R.L., Mohideen M.-A.P.K., Mest J.R., Wong A.C., Norton H.L.,
RA Aros M.C., Jurynec M.J., Mao X., Humphreville V.R., Humbert J.E., Sinha S.,
RA Moore J.L., Jagadeeswaran P., Zhao W., Ning G., Makalowska I.,
RA McKeigue P.M., O'Donnell D., Kittles R., Parra E.J., Mangini N.J.,
RA Grunwald D.J., Shriver M.D., Canfield V.A., Cheng K.C.;
RT "SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish
RT and humans.";
RL Science 310:1782-1786(2005).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [8]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND CHARACTERIZATION
RP OF VARIANT ALA-111.
RX PubMed=18166528; DOI=10.1074/jbc.m707521200;
RA Ginger R.S., Askew S.E., Ogborne R.M., Wilson S., Ferdinando D., Dadd T.,
RA Smith A.M., Kazi S., Szerencsei R.T., Winkfein R.J., Schnetkamp P.P.,
RA Green M.R.;
RT "SLC24A5 encodes a trans-Golgi network protein with potassium-dependent
RT sodium-calcium exchange activity that regulates human epidermal
RT melanogenesis.";
RL J. Biol. Chem. 283:5486-5495(2008).
RN [9]
RP INVOLVEMENT IN OCA6.
RX PubMed=23364476; DOI=10.1038/jid.2013.49;
RA Wei A.H., Zang D.J., Zhang Z., Liu X.Z., He X., Yang L., Wang Y.,
RA Zhou Z.Y., Zhang M.R., Dai L.L., Yang X.M., Li W.;
RT "Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic
RT oculocutaneous albinism.";
RL J. Invest. Dermatol. 133:1834-1840(2013).
RN [10]
RP VARIANT ALA-111, INVOLVEMENT IN SHEP4, AND POLYMORPHISM.
RX PubMed=17999355; DOI=10.1086/522235;
RA Stokowski R.P., Pant P.V.K., Dadd T., Fereday A., Hinds D.A., Jarman C.,
RA Filsell W., Ginger R.S., Green M.R., van der Ouderaa F.J., Cox D.R.;
RT "A genomewide association study of skin pigmentation in a South Asian
RT population.";
RL Am. J. Hum. Genet. 81:1119-1132(2007).
CC -!- FUNCTION: Calcium, potassium:sodium antiporter that transports 1 Ca(2+)
CC and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+)
CC (PubMed:18166528). Involved in pigmentation, possibly by participating
CC in ion transport in melanosomes (PubMed:16357253, PubMed:18166528).
CC Predominant sodium-calcium exchanger in melanocytes (PubMed:16357253,
CC PubMed:18166528). {ECO:0000269|PubMed:16357253,
CC ECO:0000269|PubMed:18166528}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Ca(2+)(out) + K(+)(out) + 4 Na(+)(in) = Ca(2+)(in) + K(+)(in)
CC + 4 Na(+)(out); Xref=Rhea:RHEA:69967, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:29103, ChEBI:CHEBI:29108;
CC Evidence={ECO:0000305|PubMed:18166528};
CC -!- INTERACTION:
CC Q71RS6; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12163679, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:18166528}; Multi-pass membrane protein
CC {ECO:0000255}. Melanosome {ECO:0000269|PubMed:17081065}. Note=Enriched
CC in late-stage melanosomes. {ECO:0000269|PubMed:17081065}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q71RS6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q71RS6-2; Sequence=VSP_047596;
CC -!- POLYMORPHISM: Genetic variants in SLC24A5 define the skin/hair/eye
CC pigmentation variation locus 4 (SHEP4) [MIM:113750]. Hair, eye and skin
CC pigmentation are among the most visible examples of human phenotypic
CC variation, with a broad normal range that is subject to substantial
CC geographic stratification. In the case of skin, individuals tend to
CC have lighter pigmentation with increasing distance from the equator. By
CC contrast, the majority of variation in human eye and hair color is
CC found among individuals of European ancestry, with most other human
CC populations fixed for brown eyes and black hair.
CC {ECO:0000269|PubMed:17999355}.
CC -!- POLYMORPHISM: The Ala-111 allele predominates (93 to 100%) in African
CC and East Asian populations. In contrast, the Thr-111 allele is nearly
CC fixed (98.7 to 100%) in European populations, is associated with a
CC substantial reduction in regional heterozygosity, and correlates with
CC lighter skin pigmentation in admixed populations.
CC {ECO:0000269|PubMed:17999355}.
CC -!- DISEASE: Albinism, oculocutaneous, 6 (OCA6) [MIM:113750]: A disorder
CC characterized by a reduction or complete loss of melanin in the skin,
CC hair and eyes. Patients show reduced or lacking pigmentation often
CC accompanied by eye symptoms such as photophobia, strabismus, moderate
CC to severe visual impairment, and nystagmus.
CC {ECO:0000269|PubMed:23364476}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC family. SLC24A subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Skin-deep - Issue 74 of
CC September 2006;
CC URL="https://web.expasy.org/spotlight/back_issues/074";
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DR EMBL; AF348468; AAQ15116.1; -; mRNA.
DR EMBL; DQ665306; ABG66958.1; -; mRNA.
DR EMBL; DQ665307; ABG66959.1; -; mRNA.
DR EMBL; AC090526; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC073944; AAH73944.1; -; mRNA.
DR EMBL; BC113628; AAI13629.1; -; mRNA.
DR EMBL; BC113630; AAI13631.1; -; mRNA.
DR EMBL; BC143950; AAI43951.1; -; mRNA.
DR CCDS; CCDS10128.1; -. [Q71RS6-1]
DR RefSeq; NP_995322.1; NM_205850.2. [Q71RS6-1]
DR AlphaFoldDB; Q71RS6; -.
DR BioGRID; 129632; 4.
DR IntAct; Q71RS6; 4.
DR STRING; 9606.ENSP00000341550; -.
DR TCDB; 2.A.19.4.6; the ca(2+):cation antiporter (caca) family.
DR iPTMnet; Q71RS6; -.
DR PhosphoSitePlus; Q71RS6; -.
DR BioMuta; SLC24A5; -.
DR DMDM; 74749781; -.
DR MassIVE; Q71RS6; -.
DR PaxDb; Q71RS6; -.
DR PeptideAtlas; Q71RS6; -.
DR PRIDE; Q71RS6; -.
DR ProteomicsDB; 68623; -. [Q71RS6-1]
DR ProteomicsDB; 754; -.
DR Antibodypedia; 24489; 98 antibodies from 28 providers.
DR DNASU; 283652; -.
DR Ensembl; ENST00000341459.8; ENSP00000341550.3; ENSG00000188467.11. [Q71RS6-1]
DR Ensembl; ENST00000449382.2; ENSP00000389966.2; ENSG00000188467.11. [Q71RS6-2]
DR GeneID; 283652; -.
DR KEGG; hsa:283652; -.
DR MANE-Select; ENST00000341459.8; ENSP00000341550.3; NM_205850.3; NP_995322.1.
DR UCSC; uc001zwe.4; human. [Q71RS6-1]
DR CTD; 283652; -.
DR DisGeNET; 283652; -.
DR GeneCards; SLC24A5; -.
DR HGNC; HGNC:20611; SLC24A5.
DR HPA; ENSG00000188467; Tissue enriched (skin).
DR MalaCards; SLC24A5; -.
DR MIM; 113750; phenotype.
DR MIM; 609802; gene.
DR neXtProt; NX_Q71RS6; -.
DR OpenTargets; ENSG00000188467; -.
DR Orphanet; 370097; Oculocutaneous albinism type 6.
DR PharmGKB; PA134868972; -.
DR VEuPathDB; HostDB:ENSG00000188467; -.
DR eggNOG; KOG1307; Eukaryota.
DR GeneTree; ENSGT01030000234532; -.
DR HOGENOM; CLU_007948_5_0_1; -.
DR InParanoid; Q71RS6; -.
DR OMA; ENMGYHA; -.
DR OrthoDB; 1168500at2759; -.
DR PhylomeDB; Q71RS6; -.
DR TreeFam; TF318759; -.
DR PathwayCommons; Q71RS6; -.
DR Reactome; R-HSA-425561; Sodium/Calcium exchangers.
DR Reactome; R-HSA-5619036; Defective SLC24A5 causes oculocutaneous albinism 6 (OCA6).
DR SignaLink; Q71RS6; -.
DR SIGNOR; Q71RS6; -.
DR BioGRID-ORCS; 283652; 11 hits in 1064 CRISPR screens.
DR ChiTaRS; SLC24A5; human.
DR GeneWiki; SLC24A5; -.
DR GenomeRNAi; 283652; -.
DR Pharos; Q71RS6; Tbio.
DR PRO; PR:Q71RS6; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q71RS6; protein.
DR Bgee; ENSG00000188467; Expressed in skin of abdomen and 48 other tissues.
DR ExpressionAtlas; Q71RS6; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IDA:MGI.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0008273; F:calcium, potassium:sodium antiporter activity; IDA:ARUK-UCL.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0070509; P:calcium ion import; IDA:ARUK-UCL.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IDA:MGI.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:Ensembl.
DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central.
DR GO; GO:0048022; P:negative regulation of melanin biosynthetic process; IEA:Ensembl.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1420.30; -; 2.
DR InterPro; IPR004481; K/Na/Ca-exchanger.
DR InterPro; IPR004837; NaCa_Exmemb.
DR InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR InterPro; IPR030245; SLC24A5.
DR PANTHER; PTHR10846; PTHR10846; 1.
DR PANTHER; PTHR10846:SF61; PTHR10846:SF61; 1.
DR Pfam; PF01699; Na_Ca_ex; 2.
DR TIGRFAMs; TIGR00367; TIGR00367; 1.
PE 1: Evidence at protein level;
KW Albinism; Alternative splicing; Antiport; Calcium; Calcium transport;
KW Golgi apparatus; Ion transport; Membrane; Potassium; Potassium transport;
KW Reference proteome; Sensory transduction; Signal; Sodium; Sodium transport;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..500
FT /note="Sodium/potassium/calcium exchanger 5"
FT /id="PRO_0000045753"
FT TOPO_DOM 30..66
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 67..87
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 88..111
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..136
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 158..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 217..302
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..333
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 334..354
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 355..368
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..399
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..420
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 421..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..468
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 469..489
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 490..500
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VAR_SEQ 41..101
FT /note="GNSTQCVISPSSEFPEGFFTRQERRDGGIIIYFLIIVYMFMAISIVCDEYFL
FT PSLEIISES -> A (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047596"
FT VARIANT 111
FT /note="T -> A (associated with SHEP4; greatly reduced
FT exchange activity; dbSNP:rs1426654)"
FT /evidence="ECO:0000269|PubMed:16357253,
FT ECO:0000269|PubMed:17999355, ECO:0000269|PubMed:18166528"
FT /id="VAR_024922"
SQ SEQUENCE 500 AA; 54888 MW; D8E91A017C9651ED CRC64;
MQTKGGQTWA RRALLLGILW ATAHLPLSGT SLPQRLPRAT GNSTQCVISP SSEFPEGFFT
RQERRDGGII IYFLIIVYMF MAISIVCDEY FLPSLEIISE SLGLSQDVAG TTFMAAGSSA
PELVTAFLGV FITKGDIGIS TILGSAIYNL LGICAACGLL SNTVSTLSCW PLFRDCAAYT
ISAAAVLGII YDNQVYWYEG ALLLLIYGLY VLVLCFDIKI NQYIIKKCSP CCACLAKAME
RSEQQPLMGW EDEGQPFIRR QSRTDSGIFY EDSGYSQLSI SLHGLSQVSE DPPSVFNMPE
ADLKRIFWVL SLPIITLLFL TTPDCRKKFW KNYFVITFFM SAIWISAFTY ILVWMVTITG
ETLEIPDTVM GLTLLAAGTS IPDTIASVLV ARKGKGDMAM SNIVGSNVFD MLCLGIPWFI
KTAFINGSAP AEVNSRGLTY ITISLNISII FLFLAVHFNG WKLDRKLGIV CLLSYLGLAT
LSVLYELGII GNNKIRGCGG
