ID NCKX4_HUMAN Reviewed; 622 AA. AC Q8NFF2; B4DHE7; B9ZVY2; Q8N8U6; Q8NCX1; Q8NFF0; Q8NFF1; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 177. 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|HGNC:HGNC:10978}; GN Synonyms=NCKX4 {ECO:0000303|PubMed:12379639}; 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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF RP 10-622 (ISOFORMS 1 AND 3), FUNCTION, TISSUE SPECIFICITY, AND TRANSPORTER RP ACTIVITY. 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] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1-474 (ISOFORM 4). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-622 (ISOFORM 1). 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 294-622 (ISOFORM 1). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP INVOLVEMENT IN SHEP6, AND POLYMORPHISM. RX PubMed=17952075; DOI=10.1038/ng.2007.13; RA Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., RA Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G., RA Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B., RA Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K., RA Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., RA Stefansson K.; RT "Genetic determinants of hair, eye and skin pigmentation in Europeans."; RL Nat. Genet. 39:1443-1452(2007). RN [8] 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). RN [9] RP FUNCTION, INVOLVEMENT IN AI2A5, AND VARIANT AI2A5 CYS-499. 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 [10] RP FUNCTION, INVOLVEMENT IN AI2A5, AND VARIANT AI2A5 VAL-146. 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). CC -!- FUNCTION: Calcium, potassium:sodium antiporter that transports 1 Ca(2+) CC and 1 K(+) in exchange for 4 Na(+) (PubMed:12379639, PubMed:26631410). CC Controls the rapid response termination and proper regulation of CC adaptation in olfactory sensory neurons (OSNs) which subsequently CC influences how odor information is encoded and perceived (By CC similarity). May play a role in calcium transport during amelogenesis CC (PubMed:23375655, PubMed:24621671). {ECO:0000250|UniProtKB:Q8CGQ8, CC ECO:0000269|PubMed:12379639, ECO:0000269|PubMed:23375655, CC ECO:0000269|PubMed:24621671, 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:0000269|PubMed:12379639, ECO:0000269|PubMed:26631410}; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26631410}; CC Multi-pass membrane protein {ECO:0000255}. Cytoplasm CC {ECO:0000250|UniProtKB:Q8CGQ8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8NFF2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8NFF2-2; Sequence=VSP_008369; CC Name=3; CC IsoId=Q8NFF2-3; Sequence=VSP_008372; CC Name=4; CC IsoId=Q8NFF2-4; Sequence=VSP_008370, VSP_008371; CC -!- TISSUE SPECIFICITY: Expressed abundantly in all regions of the brain, CC aorta, lung and thymus (PubMed:12379639). Expressed at lower levels in CC the stomach and intestine (PubMed:12379639). CC {ECO:0000269|PubMed:12379639}. CC -!- POLYMORPHISM: Genetic variants in SLC24A4 define the skin/hair/eye CC pigmentation variation locus 6 (SHEP6) [MIM:210750]. Hair, eye and skin CC pigmentation are among the most visible examples of human phenotypic CC variation, with a broad normal range that is subject to substantial CC geographic stratification. In the case of skin, individuals tend to CC have lighter pigmentation with increasing distance from the equator. By CC contrast, the majority of variation in human eye and hair color is CC found among individuals of European ancestry, with most other human CC populations fixed for brown eyes and black hair. CC {ECO:0000269|PubMed:17952075}. CC -!- DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A5 (AI2A5) CC [MIM:615887]: A defect of enamel formation. The disorder involves both CC primary and secondary dentitions. The teeth have a shiny agar jelly CC appearance and the enamel is softer than normal. Brown pigment is CC present in middle layers of enamel. {ECO:0000269|PubMed:23375655, CC ECO:0000269|PubMed:24621671}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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=AAH69653.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAM76070.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAM76071.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC04715.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC Sequence=CAD38903.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AF520704; AAM76070.1; ALT_INIT; mRNA. DR EMBL; AF520705; AAM76071.1; ALT_INIT; mRNA. DR EMBL; AF520706; AAM76072.1; -; mRNA. DR EMBL; AK096171; BAC04715.1; ALT_SEQ; mRNA. DR EMBL; AK295059; BAG58108.1; -; mRNA. DR EMBL; AL118559; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471061; EAW81485.1; -; Genomic_DNA. DR EMBL; BC069653; AAH69653.1; ALT_INIT; mRNA. DR EMBL; AL834225; CAD38903.1; ALT_INIT; mRNA. DR CCDS; CCDS45155.2; -. [Q8NFF2-3] DR CCDS; CCDS45156.1; -. [Q8NFF2-2] DR CCDS; CCDS9903.2; -. [Q8NFF2-1] DR RefSeq; NP_705932.2; NM_153646.3. [Q8NFF2-1] DR RefSeq; NP_705933.2; NM_153647.3. [Q8NFF2-3] DR RefSeq; NP_705934.1; NM_153648.3. [Q8NFF2-2] DR RefSeq; XP_011534743.1; XM_011536441.2. DR RefSeq; XP_011534744.1; XM_011536442.2. DR AlphaFoldDB; Q8NFF2; -. DR BioGRID; 125813; 2. DR STRING; 9606.ENSP00000431840; -. DR ChEMBL; CHEMBL5209636; -. DR TCDB; 2.A.19.4.5; the ca(2+):cation antiporter (caca) family. DR GlyCosmos; Q8NFF2; 2 sites, No reported glycans. DR GlyGen; Q8NFF2; 2 sites. DR iPTMnet; Q8NFF2; -. DR PhosphoSitePlus; Q8NFF2; -. DR BioMuta; SLC24A4; -. DR DMDM; 341941166; -. DR EPD; Q8NFF2; -. DR MassIVE; Q8NFF2; -. DR PaxDb; 9606-ENSP00000431840; -. DR PeptideAtlas; Q8NFF2; -. DR ProteomicsDB; 73293; -. [Q8NFF2-1] DR ProteomicsDB; 73294; -. [Q8NFF2-2] DR ProteomicsDB; 73295; -. [Q8NFF2-3] DR ProteomicsDB; 73296; -. [Q8NFF2-4] DR ABCD; Q8NFF2; 1 sequenced antibody. DR Antibodypedia; 47402; 140 antibodies from 22 providers. DR DNASU; 123041; -. DR Ensembl; ENST00000393265.6; ENSP00000376948.2; ENSG00000140090.18. [Q8NFF2-2] DR Ensembl; ENST00000531433.5; ENSP00000433302.1; ENSG00000140090.18. [Q8NFF2-3] DR Ensembl; ENST00000532405.6; ENSP00000431840.1; ENSG00000140090.18. [Q8NFF2-1] DR Ensembl; ENST00000676001.1; ENSP00000502715.1; ENSG00000140090.18. [Q8NFF2-1] DR GeneID; 123041; -. DR KEGG; hsa:123041; -. DR MANE-Select; ENST00000532405.6; ENSP00000431840.1; NM_153646.4; NP_705932.2. DR UCSC; uc001yai.4; human. [Q8NFF2-1] DR AGR; HGNC:10978; -. DR CTD; 123041; -. DR DisGeNET; 123041; -. DR GeneCards; SLC24A4; -. DR HGNC; HGNC:10978; SLC24A4. DR HPA; ENSG00000140090; Group enriched (choroid plexus, retina). DR MalaCards; SLC24A4; -. DR MIM; 210750; phenotype. DR MIM; 609840; gene. DR MIM; 615887; phenotype. DR neXtProt; NX_Q8NFF2; -. DR OpenTargets; ENSG00000140090; -. DR Orphanet; 100032; Hypocalcified amelogenesis imperfecta. DR Orphanet; 100033; Hypomaturation amelogenesis imperfecta. DR PharmGKB; PA35854; -. DR VEuPathDB; HostDB:ENSG00000140090; -. DR eggNOG; KOG1307; Eukaryota. DR GeneTree; ENSGT01030000234532; -. DR HOGENOM; CLU_007948_5_2_1; -. DR InParanoid; Q8NFF2; -. DR OMA; LFGSWGH; -. DR OrthoDB; 22570at2759; -. DR PhylomeDB; Q8NFF2; -. DR TreeFam; TF318759; -. DR PathwayCommons; Q8NFF2; -. DR Reactome; R-HSA-425561; Sodium/Calcium exchangers. DR Reactome; R-HSA-5619055; Defective SLC24A4 causes hypomineralized amelogenesis imperfecta (AI). DR SIGNOR; Q8NFF2; -. DR BioGRID-ORCS; 123041; 9 hits in 1141 CRISPR screens. DR GenomeRNAi; 123041; -. DR Pharos; Q8NFF2; Tbio. DR PRO; PR:Q8NFF2; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q8NFF2; Protein. DR Bgee; ENSG00000140090; Expressed in monocyte and 118 other cell types or tissues. DR ExpressionAtlas; Q8NFF2; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; ISS:ARUK-UCL. DR GO; GO:0120199; C:cone photoreceptor outer segment; ISS:ARUK-UCL. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL. DR GO; GO:0031982; C:vesicle; ISS: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; ISS:ARUK-UCL. DR GO; GO:0005516; F:calmodulin binding; ISS:ARUK-UCL. DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW. DR GO; GO:0097186; P:amelogenesis; ISS:UniProtKB. DR GO; GO:1990034; P:calcium ion export across plasma membrane; ISS:ARUK-UCL. DR GO; GO:0055074; P:calcium ion homeostasis; ISS:ARUK-UCL. DR GO; GO:0098703; P:calcium ion import across plasma membrane; ISS:ARUK-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:ARUK-UCL. DR GO; GO:0071486; P:cellular response to high light intensity; IEA:Ensembl. DR GO; GO:0036368; P:cone photoresponse recovery; ISS:ARUK-UCL. DR GO; GO:0050911; P:detection of chemical stimulus involved in sensory perception of smell; ISS:ARUK-UCL. DR GO; GO:0042756; P:drinking behavior; ISS:ARUK-UCL. DR GO; GO:0070166; P:enamel mineralization; TAS:ARUK-UCL. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:ARUK-UCL. DR GO; GO:0086009; P:membrane repolarization; ISS:ARUK-UCL. DR GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome. DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; ISS:ARUK-UCL. DR GO; GO:0021630; P:olfactory nerve maturation; ISS:ARUK-UCL. DR GO; GO:0007602; P:phototransduction; ISS:ARUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:ARUK-UCL. DR GO; GO:1903998; P:regulation of eating behavior; ISS:ARUK-UCL. DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; ISS:ARUK-UCL. DR GO; GO:0010469; P:regulation of signaling receptor activity; ISS:ARUK-UCL. DR GO; GO:0009644; P:response to high light intensity; ISS:ARUK-UCL. DR GO; GO:1990680; P:response to melanocyte-stimulating hormone; ISS:ARUK-UCL. DR GO; GO:1990834; P:response to odorant; ISS:ARUK-UCL. DR GO; GO:0007608; P:sensory perception of smell; ISS:UniProtKB. DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA: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:SF21; SODIUM_POTASSIUM_CALCIUM EXCHANGER 4; 1. DR Pfam; PF01699; Na_Ca_ex; 2. DR Genevisible; Q8NFF2; HS. PE 1: Evidence at protein level; KW Alternative splicing; Amelogenesis imperfecta; Antiport; Calcium; KW Calcium transport; Cell membrane; Cytoplasm; Disease variant; Glycoprotein; KW Ion transport; Membrane; Olfaction; Potassium; Potassium transport; KW Reference proteome; Repeat; Sensory transduction; Signal; Sodium; KW Sodium transport; Symport; Transmembrane; 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_0000019373" 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..410 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..408 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 69 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 76 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..109 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_008370" FT VAR_SEQ 1..64 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12379639" FT /id="VSP_008369" FT VAR_SEQ 172..210 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_008371" FT VAR_SEQ 275..293 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12379639, FT ECO:0000303|PubMed:14702039" FT /id="VSP_008372" FT VARIANT 146 FT /note="A -> V (in AI2A5; autosomal recessive; FT dbSNP:rs587777537)" FT /evidence="ECO:0000269|PubMed:24621671" FT /id="VAR_071475" FT VARIANT 499 FT /note="S -> C (in AI2A5; autosomal recessive; FT dbSNP:rs587777536)" FT /evidence="ECO:0000269|PubMed:23375655" FT /id="VAR_070183" FT VARIANT 613 FT /note="V -> I (in dbSNP:rs4900130)" FT /id="VAR_042664" FT CONFLICT 444 FT /note="C -> S (in Ref. 2; BAC04715)" FT /evidence="ECO:0000305" FT CONFLICT 560 FT /note="Y -> H (in Ref. 2; BAG58108)" FT /evidence="ECO:0000305" SQ SEQUENCE 622 AA; 69042 MW; 00D69370E55EE388 CRC64; MALRGTLRPL KVRRRREMLP QQVGFVCAVL ALVCCASGLF GSLGHKTASA SKRVLPDTWR NRKLMAPVNG TQTAKNCTDP AIHEFPTDLF SNKERQHGAV LLHILGALYM FYALAIVCDD FFVPSLEKIC ERLHLSEDVA GATFMAAGSS TPELFASVIG VFITHGDVGV GTIVGSAVFN ILCIIGVCGL FAGQVVRLTW WAVCRDSVYY TISVIVLIVF IYDEQIVWWE GLVLIILYVF YILIMKYNVK MQAFFTVKQK SIANGNPVNS ELEAGNDFYD GSYDDPSVPL LGQVKEKPQY GKNPVVMVDE IMSSSPPKFT FPEAGLRIMI TNKFGPRTRL RMASRIIINE RQRLINSANG VSSKPLQNGR HENIENGNVP VENPEDPQQN QEQQPPPQPP PPEPEPVEAD FLSPFSVPEA RGDKVKWVFT WPLIFLLCVT IPNCSKPRWE KFFMVTFITA TLWIAVFSYI MVWLVTIIGY TLGIPDVIMG ITFLAAGTSV PDCMASLIVA RQGLGDMAVS NTIGSNVFDI LVGLGVPWGL QTMVVNYGST VKINSRGLVY SVVLLLGSVA LTVLGIHLNK WRLDRKLGVY VLVLYAIFLC FSIMIEFNVF TFVNLPMCRE DD //