NCKX2_MOUSE
ID NCKX2_MOUSE Reviewed; 666 AA.
AC Q8BUN9; B1AXF2; B1AXF3; Q14AY1; Q14BI1;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Sodium/potassium/calcium exchanger 2;
DE AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 2;
DE AltName: Full=Retinal cone Na-Ca+K exchanger;
DE AltName: Full=Solute carrier family 24 member 2;
GN Name=Slc24a2 {ECO:0000312|MGI:MGI:1923626};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 2).
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16407245; DOI=10.1074/jbc.m512137200;
RA Li X.F., Kiedrowski L., Tremblay F., Fernandez F.R., Perizzolo M.,
RA Winkfein R.J., Turner R.W., Bains J.S., Rancourt D.E., Lytton J.;
RT "Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning
RT and memory.";
RL J. Biol. Chem. 281:6273-6282(2006).
CC -!- FUNCTION: Calcium, potassium:sodium antiporter that transports 1 Ca(2+)
CC and 1 K(+) in exchange for 4 Na(+) (By similarity). Required for
CC learming and memory by regulating neuronal Ca(2+), which is essential
CC for the development of synaptic plasticity (PubMed:16407245).
CC {ECO:0000250|UniProtKB:Q9UI40, ECO:0000269|PubMed:16407245}.
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:Q9UI40};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UI40};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8BUN9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BUN9-2; Sequence=VSP_061480, VSP_061481;
CC Name=3;
CC IsoId=Q8BUN9-3; Sequence=VSP_061481;
CC Name=4;
CC IsoId=Q8BUN9-4; Sequence=VSP_061481, VSP_061482;
CC Name=5;
CC IsoId=Q8BUN9-5; Sequence=VSP_061482;
CC -!- DISRUPTION PHENOTYPE: Mice display a significan reduction in Ca(2+)
CC flux in cortical neurons, leading to a profound loss of long term
CC potentiation and an increase in long term depression at hippocampal
CC Schaffer/CA1 synapses, and clear deficits in specific tests of motor
CC learning and spatial working memory (PubMed:16407245). Mice do not show
CC any obvious loss of photoreceptor function in cones (PubMed:16407245).
CC {ECO:0000269|PubMed:16407245}.
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; AK083127; BAC38773.1; -; mRNA.
DR EMBL; BC115867; AAI15868.1; -; mRNA.
DR EMBL; BC116637; AAI16638.1; -; mRNA.
DR RefSeq; NP_001103710.1; NM_001110240.1.
DR RefSeq; NP_766014.1; NM_172426.2.
DR RefSeq; XP_006538409.1; XM_006538346.3.
DR RefSeq; XP_006538412.1; XM_006538349.2.
DR AlphaFoldDB; Q8BUN9; -.
DR STRING; 10090.ENSMUSP00000102775; -.
DR GlyConnect; 2724; 1 N-Linked glycan (1 site).
DR GlyGen; Q8BUN9; 1 site, 1 N-linked glycan (1 site).
DR PhosphoSitePlus; Q8BUN9; -.
DR PaxDb; Q8BUN9; -.
DR PeptideAtlas; Q8BUN9; -.
DR ProteomicsDB; 308299; -.
DR ProteomicsDB; 332554; -.
DR ProteomicsDB; 332692; -.
DR ProteomicsDB; 373403; -.
DR Antibodypedia; 64282; 51 antibodies from 17 providers.
DR DNASU; 76376; -.
DR Ensembl; ENSMUST00000044990; ENSMUSP00000043937; ENSMUSG00000037996. [Q8BUN9-5]
DR Ensembl; ENSMUST00000107155; ENSMUSP00000102773; ENSMUSG00000037996. [Q8BUN9-4]
DR Ensembl; ENSMUST00000107157; ENSMUSP00000102775; ENSMUSG00000037996. [Q8BUN9-1]
DR Ensembl; ENSMUST00000107158; ENSMUSP00000102776; ENSMUSG00000037996. [Q8BUN9-2]
DR GeneID; 76376; -.
DR KEGG; mmu:76376; -.
DR UCSC; uc008tmk.1; mouse. [Q8BUN9-1]
DR CTD; 25769; -.
DR MGI; MGI:1923626; Slc24a2.
DR VEuPathDB; HostDB:ENSMUSG00000037996; -.
DR eggNOG; KOG1307; Eukaryota.
DR GeneTree; ENSGT01030000234532; -.
DR HOGENOM; CLU_007948_5_1_1; -.
DR InParanoid; Q8BUN9; -.
DR OMA; TIPDCRY; -.
DR OrthoDB; 1168500at2759; -.
DR PhylomeDB; Q8BUN9; -.
DR TreeFam; TF318759; -.
DR Reactome; R-MMU-425561; Sodium/Calcium exchangers.
DR BioGRID-ORCS; 76376; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Slc24a2; mouse.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8BUN9; protein.
DR Bgee; ENSMUSG00000037996; Expressed in lateral geniculate body and 85 other tissues.
DR ExpressionAtlas; Q8BUN9; baseline and differential.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005262; F:calcium channel activity; IDA:MGI.
DR GO; GO:0008273; F:calcium, potassium:sodium antiporter activity; ISO:MGI.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0070509; P:calcium ion import; ISO:MGI.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; IDA:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; ISO:MGI.
DR GO; GO:0007612; P:learning; IMP:MGI.
DR GO; GO:0060292; P:long-term synaptic depression; IMP:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:MGI.
DR GO; GO:0007613; P:memory; IMP:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
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..666
FT /note="Sodium/potassium/calcium exchanger 2"
FT /id="PRO_0000455294"
FT TOPO_DOM 1..38
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 39..59
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..133
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155..179
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 180..200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 201..205
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..260
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 261..281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 282..502
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 503..523
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 524..538
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 539..559
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 560..574
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 575..595
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 596..607
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 608..628
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 629..635
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 636..656
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 657..666
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REPEAT 175..215
FT /note="Alpha-1"
FT /evidence="ECO:0000305"
FT REPEAT 546..577
FT /note="Alpha-2"
FT /evidence="ECO:0000305"
FT REGION 63..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..443
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54701"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54701"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 311
FT /note="K -> KLSEFPPASQADGRTACPTITNDPDCQSLCFEVYPETARHGSCITNV
FT NGEPLKEKTQNSCMEE (in isoform 2)"
FT /id="VSP_061480"
FT VAR_SEQ 360..376
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /id="VSP_061481"
FT VAR_SEQ 451..455
FT /note="KATET -> T (in isoform 4 and isoform 5)"
FT /id="VSP_061482"
SQ SEQUENCE 666 AA; 74241 MW; 9FDF821097BA3875 CRC64;
MDLHQSPTAR LLQKWCSHES PFGCRRHYNS RKKLKLIRVI GLVMGLVAVS TVPFSISAFT
ETDSQSNRGE ASDMSGPRVA QGHRQRTLLD LNDKIRDYTP QPPASQEDQA ENSTEHTQGD
YPKDIFSLEE RRKGAIILHV IGMIYMFIAL AIVCDEFFVP SLTVITEKLG ISDDVAGATF
MAAGGSAPEL FTSLIGVFIA HSNVGIGTIV GSAVFNILFV IGMCALFSRE ILNLTWWPLF
RDVSFYIVDL LMLITFFLDN VIMWWESLLL LTAYFAYVVF MKFNVQVERW VKQMISRNNV
IKVTVPEAQA KSPTAGDKDG PTLPSKPRLQ RGGSSASLHN SLMRNSIFQL MIHTLDPLAE
ELGSYGKLKY YDTMTEEGRF REKASILHKI AKKKCQVDEN ERQNGAANHV EKIELPNSTS
TEVEMTPSSE ASEPVQNGNL SHNIEAADAP KATETAEEED DQPLSLSWPT NTRKQATFLI
VFPIVFPLWI TLPDVRKPAS RKFFPITFFG SITWIAVFSY LMVWWAHQVG ETIGISEEIM
GLTILAAGTS IPDLITSVIV ARKGLGDMAV SSSVGSNIFD ITVGLPLPWL LYTIIHRFSP
VTVSSNGLFC AIVLLFIMLL FVILSIALCK WRMNKILGFI MFGLYFVFLV VSVLLEDKVL
VCPVSI
