NCKX2_HUMAN
ID NCKX2_HUMAN Reviewed; 661 AA.
AC Q9UI40; B7ZLL8; Q9NTN5; Q9NZQ4;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Sodium/potassium/calcium exchanger 2;
DE AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 2 {ECO:0000303|PubMed:10662833};
DE AltName: Full=Retinal cone Na-Ca+K exchanger;
DE AltName: Full=Solute carrier family 24 member 2;
GN Name=SLC24A2; Synonyms=NCKX2 {ECO:0000303|PubMed:10662833};
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] (ISOFORMS 1 AND 2), FUNCTION, AND TRANSPORTER
RP ACTIVITY.
RC TISSUE=Retina;
RX PubMed=10662833; DOI=10.1523/jneurosci.20-04-01424.2000;
RA Prinsen C.F.M., Szerencsei R.T., Schnetkamp P.P.M.;
RT "Molecular cloning and functional expression of the potassium-dependent
RT sodium-calcium exchanger from human and chicken retinal cone
RT photoreceptors.";
RL J. Neurosci. 20:1424-1434(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [4]
RP TOPOLOGY, MUTAGENESIS OF ASN-111, AND GLYCOSYLATION AT ASN-111.
RX PubMed=12600216; DOI=10.1021/bi0270788;
RA Kinjo T.G., Szerencsei R.T., Winkfein R.J., Kang K., Schnetkamp P.P.;
RT "Topology of the retinal cone NCKX2 Na/Ca-K exchanger.";
RL Biochemistry 42:2485-2491(2003).
RN [5]
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(+) (PubMed:10662833, PubMed:26631410).
CC Required for learming and memory by regulating neuronal Ca(2+), which
CC is essential for the development of synaptic plasticity (By
CC similarity). {ECO:0000250|UniProtKB:Q8BUN9,
CC ECO:0000269|PubMed:10662833, 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:10662833, ECO:0000305|PubMed:26631410};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26631410};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UI40-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UI40-2; Sequence=VSP_006164;
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; AF097366; AAF21810.1; -; mRNA.
DR EMBL; AF177987; AAF25811.1; -; mRNA.
DR EMBL; AL158077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158206; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133281; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069622; AAH69622.1; -; mRNA.
DR EMBL; BC143889; AAI43890.1; -; mRNA.
DR CCDS; CCDS55297.1; -. [Q9UI40-2]
DR CCDS; CCDS6493.1; -. [Q9UI40-1]
DR RefSeq; NP_001180217.1; NM_001193288.2. [Q9UI40-2]
DR RefSeq; NP_065077.1; NM_020344.3. [Q9UI40-1]
DR RefSeq; XP_005251482.1; XM_005251425.2.
DR RefSeq; XP_005251483.1; XM_005251426.4.
DR RefSeq; XP_006716813.1; XM_006716750.3.
DR RefSeq; XP_016870081.1; XM_017014592.1. [Q9UI40-1]
DR RefSeq; XP_016870082.1; XM_017014593.1.
DR AlphaFoldDB; Q9UI40; -.
DR BioGRID; 117306; 1.
DR STRING; 9606.ENSP00000344801; -.
DR TCDB; 2.A.19.4.11; the ca(2+):cation antiporter (caca) family.
DR GlyGen; Q9UI40; 1 site.
DR iPTMnet; Q9UI40; -.
DR PhosphoSitePlus; Q9UI40; -.
DR BioMuta; SLC24A2; -.
DR DMDM; 17865516; -.
DR MassIVE; Q9UI40; -.
DR MaxQB; Q9UI40; -.
DR PaxDb; Q9UI40; -.
DR PeptideAtlas; Q9UI40; -.
DR PRIDE; Q9UI40; -.
DR ProteomicsDB; 84469; -. [Q9UI40-1]
DR ProteomicsDB; 84470; -. [Q9UI40-2]
DR Antibodypedia; 64282; 51 antibodies from 17 providers.
DR DNASU; 25769; -.
DR Ensembl; ENST00000286344.4; ENSP00000286344.3; ENSG00000155886.12. [Q9UI40-2]
DR Ensembl; ENST00000341998.7; ENSP00000344801.1; ENSG00000155886.12. [Q9UI40-1]
DR GeneID; 25769; -.
DR KEGG; hsa:25769; -.
DR MANE-Select; ENST00000341998.7; ENSP00000344801.1; NM_020344.4; NP_065077.1.
DR UCSC; uc003zoa.3; human. [Q9UI40-1]
DR CTD; 25769; -.
DR DisGeNET; 25769; -.
DR GeneCards; SLC24A2; -.
DR HGNC; HGNC:10976; SLC24A2.
DR HPA; ENSG00000155886; Tissue enriched (brain).
DR MIM; 609838; gene.
DR neXtProt; NX_Q9UI40; -.
DR OpenTargets; ENSG00000155886; -.
DR PharmGKB; PA35852; -.
DR VEuPathDB; HostDB:ENSG00000155886; -.
DR eggNOG; KOG1307; Eukaryota.
DR GeneTree; ENSGT01030000234532; -.
DR HOGENOM; CLU_007948_5_1_1; -.
DR InParanoid; Q9UI40; -.
DR OMA; TIPDCRY; -.
DR OrthoDB; 1168500at2759; -.
DR PhylomeDB; Q9UI40; -.
DR TreeFam; TF318759; -.
DR PathwayCommons; Q9UI40; -.
DR Reactome; R-HSA-425561; Sodium/Calcium exchangers.
DR SIGNOR; Q9UI40; -.
DR BioGRID-ORCS; 25769; 8 hits in 1064 CRISPR screens.
DR ChiTaRS; SLC24A2; human.
DR GenomeRNAi; 25769; -.
DR Pharos; Q9UI40; Tbio.
DR PRO; PR:Q9UI40; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9UI40; protein.
DR Bgee; ENSG00000155886; Expressed in endothelial cell and 80 other tissues.
DR Genevisible; Q9UI40; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0001917; C:photoreceptor inner segment; ISS: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:0070509; P:calcium ion import; IDA:ARUK-UCL.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IDA: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:0071486; P:cellular response to high light intensity; ISS:ARUK-UCL.
DR GO; GO:0036368; P:cone photoresponse recovery; ISS:ARUK-UCL.
DR GO; GO:0034220; P:ion transmembrane transport; IDA:MGI.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0060292; P:long-term synaptic depression; IBA:GO_Central.
DR GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central.
DR GO; GO:0007602; P:phototransduction; 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:0007601; P:visual perception; IEA:InterPro.
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; IPR030236; SLC24A2.
DR PANTHER; PTHR10846; PTHR10846; 1.
DR PANTHER; PTHR10846:SF41; PTHR10846:SF41; 1.
DR Pfam; PF01699; Na_Ca_ex; 2.
DR TIGRFAMs; TIGR00367; TIGR00367; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiport; Calcium; Calcium transport; Cell membrane;
KW Glycoprotein; Ion transport; Membrane; Phosphoprotein; Potassium;
KW Potassium transport; Reference proteome; Repeat; Sodium; Sodium transport;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..661
FT /note="Sodium/potassium/calcium exchanger 2"
FT /id="PRO_0000019367"
FT TOPO_DOM 1..38
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..59
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..132
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..204
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 205..225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 226..243
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 265
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 266..286
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 287..497
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 498..518
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 519..533
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 534..554
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 555..569
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 570..590
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 591..602
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 603..623
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 624..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 631..651
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 652..661
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REPEAT 174..214
FT /note="Alpha-1"
FT REPEAT 541..572
FT /note="Alpha-2"
FT REGION 99..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 306..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 412..439
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54701"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54701"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12600216"
FT VAR_SEQ 360..376
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10662833,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_006164"
FT MUTAGEN 111
FT /note="N->D: Loss of N-glycosylation."
FT /evidence="ECO:0000269|PubMed:12600216"
SQ SEQUENCE 661 AA; 73664 MW; E6359C1F95C3AB3E CRC64;
MDLQQSTTIT SLEKWCLDES LSGCRRHYSV KKKLKLIRVL GLFMGLVAIS TVSFSISAFS
ETDTQSTGEA SVVSGPRVAQ GYHQRTLLDL NDKILDYTPQ PPLSKEGESE NSTDHAQGDY
PKDIFSLEER RKGAIILHVI GMIYMFIALA IVCDEFFVPS LTVITEKLGI SDDVAGATFM
AAGGSAPELF TSLIGVFIAH SNVGIGTIVG SAVFNILFVI GMCALFSREI LNLTWWPLFR
DVSFYIVDLI MLIIFFLDNV IMWWESLLLL TAYFCYVVFM KFNVQVEKWV KQMINRNKVV
KVTAPEAQAK PSAARDKDEP TLPAKPRLQR GGSSASLHNS LMRNSIFQLM IHTLDPLAEE
LGSYGKLKYY DTMTEEGRFR EKASILHKIA KKKCHVDENE RQNGAANHVE KIELPNSTST
DVEMTPSSDA SEPVQNGNLS HNIEGAEAQT ADEEEDQPLS LAWPSETRKQ VTFLIVFPIV
FPLWITLPDV RKPSSRKFFP ITFFGSITWI AVFSYLMVWW AHQVGETIGI SEEIMGLTIL
AAGTSIPDLI TSVIVARKGL GDMAVSSSVG SNIFDITVGL PLPWLLYTVI HRFQPVAVSS
NGLFCAIVLL FIMLLFVILS IALCKWRMNK ILGFIMFGLY FVFLVVSVLL EDRILTCPVS
I
