ID   NCKX3_HUMAN             Reviewed;         644 AA.
AC   Q9HC58; B1AKV7; Q9BQJ9; Q9BQL7; Q9BQY3; Q9H519;
DT   13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 4.
DT   27-MAR-2024, entry version 178.
DE   RecName: Full=Sodium/potassium/calcium exchanger 3;
DE   AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 3 {ECO:0000303|PubMed:26631410};
DE   AltName: Full=Solute carrier family 24 member 3;
DE   Flags: Precursor;
GN   Name=SLC24A3; Synonyms=NCKX3 {ECO:0000303|PubMed:26631410};
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], FUNCTION, TISSUE SPECIFICITY, AND VARIANT
RP   ILE-55.
RC   TISSUE=Brain, and Skeletal muscle;
RX   PubMed=11294880; DOI=10.1074/jbc.m102314200;
RA   Kraev A., Quednau B.D., Leach S., Li X.-F., Dong H., Winkfein R.,
RA   Perizzolo M., Cai X., Yang R., Philipson K.D., Lytton J.;
RT   "Molecular cloning of a third member of the potassium-dependent sodium-
RT   calcium exchanger gene family, NCKX3.";
RL   J. Biol. Chem. 276:23161-23172(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [3]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=26631410; DOI=10.1016/j.ceca.2015.11.001;
RA   Jalloul A.H., Szerencsei R.T., Schnetkamp P.P.;
RT   "Cation dependencies and turnover rates of the human K(+)-dependent Na(+)-
RT   Ca(2+) exchangers NCKX1, NCKX2, NCKX3 and NCKX4.";
RL   Cell Calcium 59:1-11(2016).
CC   -!- FUNCTION: Calcium, potassium:sodium antiporter that transports 1 Ca(2+)
CC       and 1 K(+) in exchange for 4 Na(+). {ECO:0000269|PubMed:11294880,
CC       ECO:0000269|PubMed:26631410}.
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:26631410};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26631410};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Abundant in the brain (PubMed:11294880). Expressed
CC       at low levels in the aorta, uterus and intestine (PubMed:11294880).
CC       {ECO:0000269|PubMed:11294880}.
CC   -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC       family. SLC24A subfamily. {ECO:0000305}.
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DR   EMBL; AF288087; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AF169257; AAG12988.2; -; mRNA.
DR   EMBL; AL121830; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL049647; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL034425; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL121761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL139429; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL136090; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS13140.1; -.
DR   RefSeq; NP_065740.2; NM_020689.3.
DR   AlphaFoldDB; Q9HC58; -.
DR   BioGRID; 121518; 21.
DR   STRING; 9606.ENSP00000333519; -.
DR   TCDB; 2.A.19.4.10; the ca(2+):cation antiporter (caca) family.
DR   GlyCosmos; Q9HC58; 2 sites, No reported glycans.
DR   GlyGen; Q9HC58; 2 sites.
DR   iPTMnet; Q9HC58; -.
DR   PhosphoSitePlus; Q9HC58; -.
DR   BioMuta; SLC24A3; -.
DR   DMDM; 116242671; -.
DR   MassIVE; Q9HC58; -.
DR   PaxDb; 9606-ENSP00000333519; -.
DR   PeptideAtlas; Q9HC58; -.
DR   ProteomicsDB; 81642; -.
DR   Antibodypedia; 65262; 123 antibodies from 20 providers.
DR   DNASU; 57419; -.
DR   Ensembl; ENST00000328041.11; ENSP00000333519.5; ENSG00000185052.13.
DR   GeneID; 57419; -.
DR   KEGG; hsa:57419; -.
DR   MANE-Select; ENST00000328041.11; ENSP00000333519.5; NM_020689.4; NP_065740.2.
DR   UCSC; uc002wrl.4; human.
DR   AGR; HGNC:10977; -.
DR   CTD; 57419; -.
DR   DisGeNET; 57419; -.
DR   GeneCards; SLC24A3; -.
DR   HGNC; HGNC:10977; SLC24A3.
DR   HPA; ENSG00000185052; Low tissue specificity.
DR   MIM; 609839; gene.
DR   neXtProt; NX_Q9HC58; -.
DR   OpenTargets; ENSG00000185052; -.
DR   PharmGKB; PA35853; -.
DR   VEuPathDB; HostDB:ENSG00000185052; -.
DR   eggNOG; KOG1307; Eukaryota.
DR   GeneTree; ENSGT01030000234532; -.
DR   HOGENOM; CLU_007948_5_2_1; -.
DR   InParanoid; Q9HC58; -.
DR   OMA; DSVIMVC; -.
DR   OrthoDB; 22570at2759; -.
DR   PhylomeDB; Q9HC58; -.
DR   TreeFam; TF318759; -.
DR   PathwayCommons; Q9HC58; -.
DR   Reactome; R-HSA-425561; Sodium/Calcium exchangers.
DR   SIGNOR; Q9HC58; -.
DR   BioGRID-ORCS; 57419; 8 hits in 1148 CRISPR screens.
DR   ChiTaRS; SLC24A3; human.
DR   GenomeRNAi; 57419; -.
DR   Pharos; Q9HC58; Tbio.
DR   PRO; PR:Q9HC58; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; Q9HC58; Protein.
DR   Bgee; ENSG00000185052; Expressed in lateral nuclear group of thalamus and 197 other cell types or tissues.
DR   GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL.
DR   GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
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:0030282; P:bone mineralization; ISS:ARUK-UCL.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; IDA:ARUK-UCL.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:ARUK-UCL.
DR   GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome.
DR   GO; GO:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IDA:ARUK-UCL.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IDA:ARUK-UCL.
DR   GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
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:SF42; SODIUM_POTASSIUM_CALCIUM EXCHANGER 3; 1.
DR   Pfam; PF01699; Na_Ca_ex; 2.
DR   Genevisible; Q9HC58; HS.
PE   2: Evidence at transcript level;
KW   Antiport; Calcium; Calcium transport; Cell membrane; Glycoprotein;
KW   Ion transport; Membrane; Phosphoprotein; Potassium; Potassium transport;
KW   Reference proteome; Repeat; Signal; Sodium; Sodium transport; Symport;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..44
FT                   /evidence="ECO:0000255"
FT   CHAIN           45..644
FT                   /note="Sodium/potassium/calcium exchanger 3"
FT                   /id="PRO_0000019370"
FT   TOPO_DOM        45..107
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        108..128
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        129..153
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        154..174
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        175..182
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        183..203
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        204..210
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        211..231
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        232..234
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        235..255
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        256..484
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        485..505
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        506..510
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        511..531
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        532..549
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        550..570
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        571..580
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        581..601
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        602..615
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        616..636
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        637..644
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   REPEAT          149..189
FT                   /note="Alpha-1"
FT   REPEAT          518..549
FT                   /note="Alpha-2"
FT   REGION          405..442
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        408..435
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         308
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99PD7"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        86
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         49
FT                   /note="L -> P (in dbSNP:rs3790174)"
FT                   /id="VAR_028024"
FT   VARIANT         55
FT                   /note="V -> I (in dbSNP:rs1569767)"
FT                   /evidence="ECO:0000269|PubMed:11294880"
FT                   /id="VAR_028025"
FT   VARIANT         168
FT                   /note="V -> I (in dbSNP:rs3790267)"
FT                   /id="VAR_028026"
FT   VARIANT         271
FT                   /note="G -> S (in dbSNP:rs6136807)"
FT                   /id="VAR_028027"
SQ   SEQUENCE   644 AA;  71992 MW;  84247571AC2EEE7B CRC64;
     MRPSGDEDRA RRRRRRRRRR DLLLSQLCFL ASVALLLWSL SSLREQKELD LMDLVGEDRK
     WMMARKLMQV NDTLTSEDAG LRNSKNCTEP ALHEFPNDIF TNEDRRQGAV VLHVLCAIYM
     FYALAIVCDD FFVPSLEKIC ERLHLSEDVA GATFMAAGSS APELFTSVIG VFITKGDVGV
     GTIVGSAVFN ILCIIGVCGL FAGQVVALSS WCLLRDSIYY TLSVIALIVF IYDEKVSWWE
     SLVLVLMYLI YIVIMKYNAC IHQCFERRTK GAGNMVNGLA NNAEIDDSSN CDATVVLLKK
     ANFHRKASVI MVDELLSAYP HQLSFSEAGL RIMITSHFPP KTRLSMASRM LINERQRLIN
     SRAYTNGESE VAIKIPIKHT VENGTGPSSA PDRGVNGTRR DDVVAEAGNE TENENEDNEN
     DEEEEEDEDD DEGPYTPFDT PSGKLETVKW AFTWPLSFVL YFTVPNCNKP RWEKWFMVTF
     ASSTLWIAAF SYMMVWMVTI IGYTLGIPDV IMGITFLAAG TSVPDCMASL IVARQGMGDM
     AVSNSIGSNV FDILIGLGLP WALQTLAVDY GSYIRLNSRG LIYSVGLLLA SVFVTVFGVH
     LNKWQLDKKL GCGCLLLYGV FLCFSIMTEF NVFTFVNLPM CGDH
//