NCKX3_HUMAN
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 03-AUG-2022, entry version 169.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; Q9HC58; 2 sites.
DR iPTMnet; Q9HC58; -.
DR PhosphoSitePlus; Q9HC58; -.
DR BioMuta; SLC24A3; -.
DR DMDM; 116242671; -.
DR MassIVE; Q9HC58; -.
DR PaxDb; Q9HC58; -.
DR PeptideAtlas; Q9HC58; -.
DR PRIDE; Q9HC58; -.
DR ProteomicsDB; 81642; -.
DR Antibodypedia; 65262; 115 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 CTD; 57419; -.
DR DisGeNET; 57419; -.
DR GeneCards; SLC24A3; -.
DR HGNC; HGNC:10977; SLC24A3.
DR HPA; ENSG00000185052; Tissue enhanced (brain).
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; YDERVSW; -.
DR OrthoDB; 1168500at2759; -.
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 1070 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 195 other tissues.
DR Genevisible; Q9HC58; HS.
DR GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:cellular calcium ion homeostasis; IDA:ARUK-UCL.
DR GO; GO:0006811; P: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; -; 2.
DR InterPro; IPR004481; K/Na/Ca-exchanger.
DR InterPro; IPR004837; NaCa_Exmemb.
DR InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR InterPro; IPR030248; SLC24A3.
DR PANTHER; PTHR10846; PTHR10846; 1.
DR PANTHER; PTHR10846:SF22; PTHR10846:SF22; 1.
DR Pfam; PF01699; Na_Ca_ex; 2.
DR TIGRFAMs; TIGR00367; TIGR00367; 1.
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
