ID   NCKX5_DANRE             Reviewed;         513 AA.
AC   Q49SH1; Q49P06; Q592E6;
DT   10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   13-SEP-2005, sequence version 1.
DT   27-MAR-2024, entry version 101.
DE   RecName: Full=Sodium/potassium/calcium exchanger 5;
DE   AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 5;
DE   AltName: Full=Protein golden;
DE   AltName: Full=Solute carrier family 24 member 5;
DE   Flags: Precursor;
GN   Name=slc24a5; Synonyms=nckx5;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, SUBCELLULAR LOCATION,
RP   TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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   [2]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=19414594; DOI=10.1128/mcb.00177-09;
RA   Wittkopp N., Huntzinger E., Weiler C., Sauliere J., Schmidt S.,
RA   Sonawane M., Izaurralde E.;
RT   "Nonsense-mediated mRNA decay effectors are essential for zebrafish
RT   embryonic development and survival.";
RL   Mol. Cell. Biol. 29:3517-3528(2009).
CC   -!- FUNCTION: Calcium, potassium:sodium antiporter that transports 1 Ca(2+)
CC       and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+) (By
CC       similarity). Involved in pigmentation, possibly by participating in ion
CC       transport in melanosomes (PubMed:16357253). Predominant sodium-calcium
CC       exchanger in melanocytes (PubMed:16357253).
CC       {ECO:0000250|UniProtKB:Q71RS6, ECO:0000269|PubMed:16357253}.
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:0000250|UniProtKB:Q71RS6};
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC       {ECO:0000305|PubMed:16357253}; Multi-pass membrane protein
CC       {ECO:0000255}. Melanosome {ECO:0000305|PubMed:16357253}. Note=Enriched
CC       in late-stage melanosomes. {ECO:0000250|UniProtKB:Q71RS6}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in melanin-producing cells.
CC       Colocalizes with melanin biosynthesis marker dct.
CC       {ECO:0000269|PubMed:16357253}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the retinal pigment epithelium and in
CC       the melanopore precursors at 1 day post-fertilization.
CC       {ECO:0000269|PubMed:19414594}.
CC   -!- DISRUPTION PHENOTYPE: Fishes show a delayed and reduced development of
CC       pigmentation. They display a diminished number, size and density of
CC       melanosomes. {ECO:0000269|PubMed:16357253}.
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; AY538713; AAY89721.1; -; mRNA.
DR   EMBL; AY581204; AAS76476.1; -; Genomic_DNA.
DR   EMBL; AY682553; AAY89722.1; -; mRNA.
DR   RefSeq; NP_001025451.1; NM_001030280.1.
DR   AlphaFoldDB; Q49SH1; -.
DR   STRING; 7955.ENSDARP00000030499; -.
DR   PaxDb; 7955-ENSDARP00000030499; -.
DR   GeneID; 570312; -.
DR   KEGG; dre:570312; -.
DR   AGR; ZFIN:ZDB-GENE-031210-1; -.
DR   CTD; 283652; -.
DR   ZFIN; ZDB-GENE-031210-1; slc24a5.
DR   eggNOG; KOG1307; Eukaryota.
DR   InParanoid; Q49SH1; -.
DR   OrthoDB; 22570at2759; -.
DR   PhylomeDB; Q49SH1; -.
DR   PRO; PR:Q49SH1; -.
DR   Proteomes; UP000000437; Chromosome 18.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR   GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR   GO; GO:0008273; F:calcium, potassium:sodium antiporter activity; IBA:GO_Central.
DR   GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0048066; P:developmental pigmentation; IMP:ZFIN.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; IBA:GO_Central.
DR   GO; GO:0030318; P:melanocyte differentiation; IMP:ZFIN.
DR   GO; GO:0097324; P:melanocyte migration; IMP:ZFIN.
DR   GO; GO:0043473; P:pigmentation; IMP:ZFIN.
DR   GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR   Gene3D; 1.20.1420.30; NCX, central ion-binding region; 2.
DR   InterPro; IPR004481; K/Na/Ca-exchanger.
DR   InterPro; IPR004837; NaCa_Exmemb.
DR   InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR   NCBIfam; TIGR00367; calcium/sodium antiporter; 1.
DR   PANTHER; PTHR10846; SODIUM/POTASSIUM/CALCIUM EXCHANGER; 1.
DR   PANTHER; PTHR10846:SF61; SODIUM_POTASSIUM_CALCIUM EXCHANGER 5; 1.
DR   Pfam; PF01699; Na_Ca_ex; 2.
PE   2: Evidence at transcript level;
KW   Antiport; Calcium; Calcium transport; Golgi apparatus; Ion transport;
KW   Membrane; Potassium; Potassium transport; Reference proteome;
KW   Sensory transduction; Signal; Sodium; Sodium transport; Symport;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..35
FT                   /evidence="ECO:0000255"
FT   CHAIN           36..513
FT                   /note="Sodium/potassium/calcium exchanger 5"
FT                   /id="PRO_0000045755"
FT   TOPO_DOM        36..78
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        79..99
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        100..123
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        124..144
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        145..148
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        149..169
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        170..181
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        182..202
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        203..207
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        208..228
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        229..315
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        316..336
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        337..350
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        351..371
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        372..381
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        382..402
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        403..420
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        421..441
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        442..450
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        451..471
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        472..482
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        483..503
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        504..513
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        192
FT                   /note="A -> S (in Ref. 1; AAS76476)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        231
FT                   /note="R -> K (in Ref. 1; AAS76476)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        445
FT                   /note="E -> D (in Ref. 1; AAS76476)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        477
FT                   /note="D -> N (in Ref. 1; AAY89722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        512
FT                   /note="S -> R (in Ref. 1; AAY89722)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   513 AA;  56782 MW;  42023F56CFB37045 CRC64;
     MRTDVFLQRR KRRDVLLSII ALLLLIFAIV HLVFCAGLSF QGSSSARVRR DLENASECVQ
     PQSSEFPEGF FTVQERKDGG ILIYFMIIFY MLLSVSIVCD EYFLPSLEVI SERLGLSQDV
     AGATFMAAGS SAPELVTAFL GVFVTKGDIG VSTIMGSAVY NLLCICAACG LLSSAVGRLS
     CWPLFRDCVA YAISVAAVIA IISDNRVYWY DGACLLLVYG VYVAVLCFDL RISEYVMQRF
     SPCCWCLKPR DRDSGEQQPL VGWSDDSSLR VQRRSRNDSG IFQDDSGYSH LSLSLHGLNE
     ISDEHKSVFS MPDHDLKRIL WVLSLPVSTL LFVSVPDCRR PFWKNFYMLT FLMSAVWISA
     FTYVLVWMVT IVGETLGIPD TVMGMTLLAA GTSIPDTVAS VMVAREGKSD MAMSNIVGSN
     VFDMLCLGLP WFIQTVFVDV GSPVEVNSSG LVFMSCTLLL SIIFLFLAVH INGWKLDWKL
     GLVCLACYIL FATLSILYEL GIIGNNPIRS CSD
//