NCKX4_MOUSE
ID NCKX4_MOUSE Reviewed; 622 AA.
AC Q8CGQ8; Q8BLL5; Q8BLL7;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Sodium/potassium/calcium exchanger 4;
DE AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 4 {ECO:0000303|PubMed:12379639};
DE AltName: Full=Solute carrier family 24 member 4;
DE Flags: Precursor;
GN Name=Slc24a4 {ECO:0000312|MGI:MGI:2447362};
GN Synonyms=Nckx4 {ECO:0000303|PubMed:12379639};
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 [MRNA] OF 11-622 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=12379639; DOI=10.1074/jbc.m210011200;
RA Li X.-F., Kraev A.S., Lytton J.;
RT "Molecular cloning of a fourth member of the potassium-dependent sodium-
RT calcium exchanger gene family, NCKX4.";
RL J. Biol. Chem. 277:48410-48417(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-573 (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-257 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Retina;
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=22677781; DOI=10.1159/000337493;
RA Hu P., Lacruz R.S., Smith C.E., Smith S.M., Kurtz I., Paine M.L.;
RT "Expression of the sodium/calcium/potassium exchanger, NCKX4, in
RT ameloblasts.";
RL Cells Tissues Organs 196:501-509(2012).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22057188; DOI=10.1038/nn.2943;
RA Stephan A.B., Tobochnik S., Dibattista M., Wall C.M., Reisert J., Zhao H.;
RT "The Na(+)/Ca(2+) exchanger NCKX4 governs termination and adaptation of the
RT mammalian olfactory response.";
RL Nat. Neurosci. 15:131-137(2012).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23375655; DOI=10.1016/j.ajhg.2013.01.003;
RA Parry D.A., Poulter J.A., Logan C.V., Brookes S.J., Jafri H.,
RA Ferguson C.H., Anwari B.M., Rashid Y., Zhao H., Johnson C.A.,
RA Inglehearn C.F., Mighell A.J.;
RT "Identification of mutations in SLC24A4, encoding a potassium-dependent
RT sodium/calcium exchanger, as a cause of amelogenesis imperfecta.";
RL Am. J. Hum. Genet. 92:307-312(2013).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24621671; DOI=10.1177/0022034514527971;
RA Wang S., Choi M., Richardson A.S., Reid B.M., Seymen F., Yildirim M.,
RA Tuna E., Gencay K., Simmer J.P., Hu J.C.;
RT "STIM1 and SLC24A4 are critical for enamel maturation.";
RL J. Dent. Res. 93:94S-100S(2014).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=26247047; DOI=10.1002/mgg3.143;
RA Wang S.K., Hu Y., Yang J., Smith C.E., Nunez S.M., Richardson A.S., Pal S.,
RA Samann A.C., Hu J.C., Simmer J.P.;
RT "Critical roles for WDR72 in calcium transport and matrix protein removal
RT during enamel maturation.";
RL Mol. Genet. Genomic Med. 3:302-319(2015).
CC -!- FUNCTION: Calcium, potassium:sodium antiporter that transports 1 Ca(2+)
CC and 1 K(+) in exchange for 4 Na(+) (PubMed:22057188). Controls the
CC rapid response termination and proper regulation of adaptation in
CC olfactory sensory neurons (OSNs) which subsequently influences how odor
CC information is encoded and perceived (PubMed:22057188). May play a role
CC in calcium transport during amelogenesis (PubMed:23375655).
CC {ECO:0000269|PubMed:22057188, ECO:0000269|PubMed:23375655}.
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:Q8NFF2};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24621671,
CC ECO:0000269|PubMed:26247047}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:24621671,
CC ECO:0000269|PubMed:26247047}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CGQ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CGQ8-2; Sequence=VSP_041610, VSP_041611;
CC -!- TISSUE SPECIFICITY: Expressed in late secretory-stage and maturation-
CC stage ameloblasts, with significantly increased expression during the
CC late stages of amelogenesis (at protein level) (PubMed:22677781,
CC PubMed:24621671, PubMed:26247047). Widely expressed in most regions of
CC the brain, including hippocampus, neocortex, thalamus, striatum and
CC olfactory bulb (PubMed:12379639). Expressed in the olfactory sensory
CC neurons (PubMed:22057188). {ECO:0000269|PubMed:22057188,
CC ECO:0000269|PubMed:22677781, ECO:0000269|PubMed:24621671,
CC ECO:0000269|PubMed:26247047}.
CC -!- DISRUPTION PHENOTYPE: Mice have a reduced ability to locate an odorous
CC source and lower body weights. The olfactory sensory neurons display
CC defects in response termination and adaptation but have unchanged
CC sensitivity (PubMed:22057188). Mice show severe enamel defects
CC (PubMed:23375655). {ECO:0000269|PubMed:22057188,
CC ECO:0000269|PubMed:23375655}.
CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC family. SLC24A subfamily. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-18 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN37415.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC31835.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC31835.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AY156046; AAN37415.1; ALT_INIT; mRNA.
DR EMBL; AK044239; BAC31835.1; ALT_SEQ; mRNA.
DR EMBL; AK044368; BAC31887.1; -; mRNA.
DR CCDS; CCDS26117.2; -. [Q8CGQ8-1]
DR RefSeq; NP_742164.1; NM_172152.2. [Q8CGQ8-1]
DR AlphaFoldDB; Q8CGQ8; -.
DR STRING; 10090.ENSMUSP00000078030; -.
DR GlyGen; Q8CGQ8; 1 site.
DR iPTMnet; Q8CGQ8; -.
DR PhosphoSitePlus; Q8CGQ8; -.
DR MaxQB; Q8CGQ8; -.
DR PaxDb; Q8CGQ8; -.
DR PRIDE; Q8CGQ8; -.
DR ProteomicsDB; 252927; -. [Q8CGQ8-1]
DR ProteomicsDB; 252928; -. [Q8CGQ8-2]
DR Antibodypedia; 47402; 108 antibodies from 22 providers.
DR DNASU; 238384; -.
DR Ensembl; ENSMUST00000079020; ENSMUSP00000078030; ENSMUSG00000041771. [Q8CGQ8-1]
DR GeneID; 238384; -.
DR KEGG; mmu:238384; -.
DR UCSC; uc007oty.1; mouse. [Q8CGQ8-1]
DR CTD; 123041; -.
DR MGI; MGI:2447362; Slc24a4.
DR VEuPathDB; HostDB:ENSMUSG00000041771; -.
DR eggNOG; KOG1307; Eukaryota.
DR GeneTree; ENSGT01030000234532; -.
DR InParanoid; Q8CGQ8; -.
DR OrthoDB; 1168500at2759; -.
DR TreeFam; TF318759; -.
DR Reactome; R-MMU-425561; Sodium/Calcium exchangers.
DR BioGRID-ORCS; 238384; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Slc24a4; mouse.
DR PRO; PR:Q8CGQ8; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8CGQ8; protein.
DR Bgee; ENSMUSG00000041771; Expressed in retinal neural layer and 44 other tissues.
DR ExpressionAtlas; Q8CGQ8; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0120199; C:cone photoreceptor outer segment; IDA:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0031982; C:vesicle; 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:0048306; F:calcium-dependent protein binding; IPI:ARUK-UCL.
DR GO; GO:0005432; F:calcium:sodium antiporter activity; ISA:MGI.
DR GO; GO:0005516; F:calmodulin binding; IPI:ARUK-UCL.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0097186; P:amelogenesis; IMP:UniProtKB.
DR GO; GO:1990034; P:calcium ion export across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP: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; ISO:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
DR GO; GO:0071486; P:cellular response to high light intensity; IMP:ARUK-UCL.
DR GO; GO:0036368; P:cone photoresponse recovery; IMP:ARUK-UCL.
DR GO; GO:0050911; P:detection of chemical stimulus involved in sensory perception of smell; IMP:ARUK-UCL.
DR GO; GO:0042756; P:drinking behavior; IMP:ARUK-UCL.
DR GO; GO:0086009; P:membrane repolarization; IMP:ARUK-UCL.
DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; IDA:ARUK-UCL.
DR GO; GO:0021630; P:olfactory nerve maturation; IMP:ARUK-UCL.
DR GO; GO:0007602; P:phototransduction; IMP:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:1903998; P:regulation of eating behavior; IMP:ARUK-UCL.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0010469; P:regulation of signaling receptor activity; IMP:ARUK-UCL.
DR GO; GO:1990680; P:response to melanocyte-stimulating hormone; IMP:ARUK-UCL.
DR GO; GO:1990834; P:response to odorant; IMP:ARUK-UCL.
DR GO; GO:0007608; P:sensory perception of smell; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
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; IPR030232; SLC24A4.
DR PANTHER; PTHR10846; PTHR10846; 1.
DR PANTHER; PTHR10846:SF21; PTHR10846:SF21; 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 Cytoplasm; Glycoprotein; Ion transport; Membrane; Olfaction; Potassium;
KW Potassium transport; Reference proteome; Repeat; Sensory transduction;
KW Signal; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..38
FT /evidence="ECO:0000255"
FT CHAIN 39..622
FT /note="Sodium/potassium/calcium exchanger 4"
FT /id="PRO_0000019374"
FT TOPO_DOM 39..97
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 98..118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..142
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 143..163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..172
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..224
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 246..457
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 479
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..526
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 527..547
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 548..557
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 558..578
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 579..586
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 587..607
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 608..622
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REPEAT 139..179
FT /note="Alpha-1"
FT REPEAT 495..526
FT /note="Alpha-2"
FT REGION 358..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 358..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 390..407
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 275..293
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_041610"
FT VAR_SEQ 574..622
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_041611"
FT CONFLICT 430
FT /note="T -> M (in Ref. 2; BAC31835)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 622 AA; 68974 MW; 53D25851573F9D27 CRC64;
MALRGLIRQS KVRRRREMLP QQVGFVCAVL ALVCCASGLF GSLGHKTASA GKHVLLDTWR
NRKLMAPING TPLAKNCTDP AIHEFPTDLF SNKERQHGAV LLHILGALYM FYALAIVCDD
FFVPSLEKIC EKLHLSEDVA GATFMAAGSS TPELFASVIG VFITHGDVGV GTIVGSAVFN
ILCIIGVCGL FAGQVVRLTW WAVCRDSVYY TLSVIVLIAF IYDEEIVWWE GLVLIILYVF
YILIMKYNMK MQTFFTTKQK SIANGNPVSN ELEDGNDLYD GSYDDPSVPL LGQVKEKPPY
GKTPVVMVDE ILSSSPPKFT FPEAGLRIMI TNKFGPRTRL RMASRIIINE RQRLINSANG
VNSKPLQNGR HENMENGNVP VENPEDPQQG QEQQPPPQPP PPEPESVETV FLSPFSMPEA
KGDKAKWVFT WPLIFLLCVT IPNCSKPRWE KFFMVTFITA TLWIAVFSYL MVWLVTIIGY
TLGIPDVIMG ITFLAAGTSV PDCMASLIVA RQGLGDMAVS NTIGSNVFDI LVGLGIPWGL
QTMVINYGST VKINSRGLVY SVVLLLGSVA LTVLGIHLNK WRLDRKLGIY VLVLYAVFLC
FSIMIEFNVF TFVNLPMCRE DD
