ID NCKX1_HUMAN Reviewed; 1099 AA. AC O60721; O43485; O75184; Q17RM9; DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 13-FEB-2019, entry version 159. DE RecName: Full=Sodium/potassium/calcium exchanger 1; DE AltName: Full=Na(+)/K(+)/Ca(2+)-exchange protein 1; DE AltName: Full=Retinal rod Na-Ca+K exchanger; DE AltName: Full=Solute carrier family 24 member 1; GN Name=SLC24A1; Synonyms=KIAA0702, NCKX1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=9856482; DOI=10.1007/s004390050842; RA Tucker J.E., Winkfein R.J., Murthy S.K., Friedman J.S., Walter M.A., RA Demetrick D.J., Schnetkamp P.P.M.; RT "Chromosomal localization and genomic organization of the human RT retinal rod Na-Ca+K exchanger."; RL Hum. Genet. 103:411-414(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Retina; RX PubMed=9478004; RA Tucker J.E., Winkfein R.J., Cooper C.B., Schnetkamp P.P.M.; RT "cDNA cloning of the human retinal rod Na-Ca + K exchanger: comparison RT with a revised bovine sequence."; RL Invest. Ophthalmol. Vis. Sci. 39:435-440(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., RA Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human RT chromosome 15."; RL Nature 440:671-675(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Heart, and Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1003 (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9734811; DOI=10.1093/dnares/5.3.169; RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. X. RT The complete sequences of 100 new cDNA clones from brain which can RT code for large proteins in vitro."; RL DNA Res. 5:169-176(1998). RN [6] RP FUNCTION OF THE N-TERMINUS IN TARGETING. RX PubMed=10608890; DOI=10.1074/jbc.274.53.38177; RA McKiernan C.J., Friedlander M.; RT "The retinal rod Na(+)/Ca(2+),K(+) exchanger contains a noncleaved RT signal sequence required for translocation of the N-terminus."; RL J. Biol. Chem. 274:38177-38182(1999). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-724, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP TISSUE SPECIFICITY, AND INVOLVEMENT IN CSNB1D. RX PubMed=20850105; DOI=10.1016/j.ajhg.2010.08.013; RA Riazuddin S.A., Shahzadi A., Zeitz C., Ahmed Z.M., Ayyagari R., RA Chavali V.R., Ponferrada V.G., Audo I., Michiels C., Lancelot M.E., RA Nasir I.A., Zafar A.U., Khan S.N., Husnain T., Jiao X., RA MacDonald I.M., Riazuddin S., Sieving P.A., Katsanis N., RA Hejtmancik J.F.; RT "A mutation in SLC24A1 implicated in autosomal-recessive congenital RT stationary night blindness."; RL Am. J. Hum. Genet. 87:523-531(2010). CC -!- FUNCTION: Critical component of the visual transduction cascade, CC controlling the calcium concentration of outer segments during CC light and darkness. Light causes a rapid lowering of cytosolic CC free calcium in the outer segment of both retinal rod and cone CC photoreceptors and the light-induced lowering of calcium is caused CC by extrusion via this protein which plays a key role in the CC process of light adaptation. Transports 1 Ca(2+) and 1 K(+) in CC exchange for 4 Na(+). {ECO:0000269|PubMed:10608890}. CC -!- INTERACTION: CC P16333:NCK1; NbExp=3; IntAct=EBI-1753504, EBI-389883; CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O60721-1; Sequence=Displayed; CC Name=2; CC IsoId=O60721-2; Sequence=VSP_006160; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=O60721-3; Sequence=VSP_054491; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in the retina, particularly in the CC inner segment, outer and inner nuclear layers, and ganglion cell CC layer. {ECO:0000269|PubMed:20850105}. CC -!- PTM: The uncleaved signal sequence is required for efficient CC membrane targeting and proper membrane integration. CC -!- DISEASE: Night blindness, congenital stationary, 1D (CSNB1D) CC [MIM:613830]: An autosomal recessive form of congenital stationary CC night blindness, a non-progressive retinal disorder characterized CC by impaired night vision. CSNB1D is characterized by a Riggs type CC of electroretinogram (proportionally reduced a- and b-waves). CC Patients have visual acuity within the normal range and no CC symptoms of myopia and/or nystagmus. CC {ECO:0000269|PubMed:20850105}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC CC 2.A.19) 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; AF062921; AAC16732.1; -; mRNA. DR EMBL; AF062922; AAC77912.1; -; mRNA. DR EMBL; AF026132; AAB97832.1; -; mRNA. DR EMBL; AC011939; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC027220; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC117263; AAI17264.1; -; mRNA. DR EMBL; BC143375; AAI43376.1; -; mRNA. DR EMBL; AB014602; BAA31677.2; ALT_SEQ; mRNA. DR CCDS; CCDS45284.1; -. [O60721-1] DR CCDS; CCDS73742.1; -. [O60721-3] DR CCDS; CCDS73743.1; -. [O60721-2] DR RefSeq; NP_001287960.1; NM_001301031.1. [O60721-3] DR RefSeq; NP_001287961.1; NM_001301032.1. [O60721-2] DR RefSeq; NP_001287962.1; NM_001301033.1. DR RefSeq; NP_004718.1; NM_004727.2. [O60721-1] DR RefSeq; XP_005254835.1; XM_005254778.3. [O60721-1] DR RefSeq; XP_011520521.1; XM_011522219.1. [O60721-1] DR RefSeq; XP_011520522.1; XM_011522220.2. [O60721-2] DR RefSeq; XP_011520523.1; XM_011522221.2. [O60721-3] DR UniGene; Hs.173092; -. DR UniGene; Hs.617821; -. DR ProteinModelPortal; O60721; -. DR SMR; O60721; -. DR BioGrid; 114624; 2. DR IntAct; O60721; 5. DR STRING; 9606.ENSP00000261892; -. DR TCDB; 2.A.19.4.9; the ca(2+):cation antiporter (caca) family. DR iPTMnet; O60721; -. DR PhosphoSitePlus; O60721; -. DR BioMuta; SLC24A1; -. DR jPOST; O60721; -. DR MaxQB; O60721; -. DR PaxDb; O60721; -. DR PeptideAtlas; O60721; -. DR PRIDE; O60721; -. DR ProteomicsDB; 49569; -. DR ProteomicsDB; 49570; -. [O60721-2] DR Ensembl; ENST00000261892; ENSP00000261892; ENSG00000074621. [O60721-1] DR Ensembl; ENST00000339868; ENSP00000341837; ENSG00000074621. [O60721-3] DR Ensembl; ENST00000399033; ENSP00000381991; ENSG00000074621. [O60721-3] DR Ensembl; ENST00000546330; ENSP00000439190; ENSG00000074621. [O60721-2] DR GeneID; 9187; -. DR KEGG; hsa:9187; -. DR UCSC; uc010ujf.2; human. [O60721-1] DR CTD; 9187; -. DR DisGeNET; 9187; -. DR EuPathDB; HostDB:ENSG00000074621.13; -. DR GeneCards; SLC24A1; -. DR HGNC; HGNC:10975; SLC24A1. DR HPA; HPA039370; -. DR MalaCards; SLC24A1; -. DR MIM; 603617; gene. DR MIM; 613830; phenotype. DR neXtProt; NX_O60721; -. DR OpenTargets; ENSG00000074621; -. DR Orphanet; 215; Congenital stationary night blindness. DR PharmGKB; PA35851; -. DR eggNOG; KOG1307; Eukaryota. DR eggNOG; ENOG410Y9YY; LUCA. DR GeneTree; ENSGT00940000153508; -. DR HOGENOM; HOG000231933; -. DR HOVERGEN; HBG104097; -. DR InParanoid; O60721; -. DR KO; K13749; -. DR OMA; PSEEMMM; -. DR OrthoDB; 309052at2759; -. DR PhylomeDB; O60721; -. DR TreeFam; TF318759; -. DR Reactome; R-HSA-2485179; Activation of the phototransduction cascade. DR Reactome; R-HSA-425561; Sodium/Calcium exchangers. DR Reactome; R-HSA-5619077; Defective SLC24A1 causes congenital stationary night blindness 1D (CSNB1D). DR ChiTaRS; SLC24A1; human. DR GenomeRNAi; 9187; -. DR PRO; PR:O60721; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; ENSG00000074621; Expressed in 159 organ(s), highest expression level in amniotic fluid. DR ExpressionAtlas; O60721; baseline and differential. DR Genevisible; O60721; HS. DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0019867; C:outer membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central. DR GO; GO:0008273; F:calcium, potassium:sodium antiporter activity; IBA:GO_Central. DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW. DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central. DR GO; GO:0006816; P:calcium ion transport; NAS:UniProtKB. DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central. 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:0009642; P:response to light intensity; NAS:UniProtKB. DR GO; GO:0007601; P:visual perception; NAS:UniProtKB. DR InterPro; IPR004481; K/Na/Ca-exchanger. DR InterPro; IPR004837; NaCa_Exmemb. DR InterPro; IPR004817; SLC24A1. DR PANTHER; PTHR10846; PTHR10846; 1. DR Pfam; PF01699; Na_Ca_ex; 2. DR TIGRFAMs; TIGR00927; 2A1904; 1. DR TIGRFAMs; TIGR00367; TIGR00367; 1. PE 1: Evidence at protein level; KW Alternative splicing; Antiport; Calcium; Calcium transport; KW Complete proteome; Congenital stationary night blindness; KW Glycoprotein; Ion transport; Membrane; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Sensory transduction; Signal; Symport; KW Transmembrane; Transmembrane helix; Transport; Vision. FT CHAIN 1 1099 Sodium/potassium/calcium exchanger 1. FT /FTId=PRO_0000223303. FT SIGNAL 1 ? Not cleaved. FT TOPO_DOM 1 452 Extracellular. {ECO:0000255}. FT TRANSMEM 453 473 Helical. {ECO:0000255}. FT TOPO_DOM 474 497 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 498 518 Helical. {ECO:0000255}. FT TOPO_DOM 519 522 Extracellular. {ECO:0000255}. FT TRANSMEM 523 543 Helical. {ECO:0000255}. FT TOPO_DOM 544 563 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 564 584 Helical. {ECO:0000255}. FT TOPO_DOM 585 585 Extracellular. {ECO:0000255}. FT TRANSMEM 586 606 Helical. {ECO:0000255}. FT TOPO_DOM 607 907 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 908 928 Helical. {ECO:0000255}. FT TOPO_DOM 929 935 Extracellular. {ECO:0000255}. FT TRANSMEM 936 956 Helical. {ECO:0000255}. FT TOPO_DOM 957 971 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 972 992 Helical. {ECO:0000255}. FT TOPO_DOM 993 1010 Extracellular. {ECO:0000255}. FT TRANSMEM 1011 1031 Helical. {ECO:0000255}. FT TOPO_DOM 1032 1039 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1040 1060 Helical. {ECO:0000255}. FT TOPO_DOM 1061 1068 Extracellular. {ECO:0000255}. FT TRANSMEM 1069 1089 Helical. {ECO:0000255}. FT TOPO_DOM 1090 1099 Cytoplasmic. {ECO:0000255}. FT REPEAT 494 534 Alpha-1. FT REPEAT 979 1010 Alpha-2. FT COMPBIAS 860 890 Poly-Glu. FT MOD_RES 658 658 Phosphoserine. {ECO:0000255}. FT MOD_RES 724 724 Phosphothreonine. FT {ECO:0000244|PubMed:19690332}. FT CARBOHYD 290 290 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VAR_SEQ 631 648 Missing (in isoform 2). FT {ECO:0000303|PubMed:9478004, FT ECO:0000303|PubMed:9734811}. FT /FTId=VSP_006160. FT VAR_SEQ 932 961 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_054491. FT VARIANT 37 37 T -> S (in dbSNP:rs3743171). FT /FTId=VAR_050221. FT VARIANT 311 311 V -> L (in dbSNP:rs34363823). FT /FTId=VAR_050222. FT VARIANT 313 313 L -> V (in dbSNP:rs35571449). FT /FTId=VAR_050223. FT CONFLICT 516 516 V -> I (in Ref. 2; AAB97832). FT {ECO:0000305}. SQ SEQUENCE 1099 AA; 121374 MW; 3911856BB088B5FD CRC64; MGKLIRMGPQ ERWLLRTKRL HWSRLLFLLG MLIIGSTYQH LRRPRGLSSL WAAVSSHQPI KLASRDLSSE EMMMMSSSPS KPSSEMGGKM LVPQASVGSD EATLSMTVEN IPSMPKRTAK MIPTTTKNNY SPTAAGTERR KEDTPTSSRT LTYYTSTSSR QIVKKYTPTP RGEMKSYSPT QVREKVKYTP SPRGRRVGTY VPSTFMTMET SHAITPRTTV KDSDITATYK ILETNSLKRI MEETTPTTLK GMFDSTPTFL THEVEANVLT SPRSVMEKNN LFPPRRVESN SSAHPWGLVG KSNPKTPQGT VLLHTPATSE GQVTISTMTG SSPAETKAFT AAWSLRNPSP RTSVSAIKTA PAIVWRLAKK PSTAPSTSTT PTVRAKLTMQ VHHCVVVKPT PAMLTTPSPS LTTALLPEEL SPSPSVLPPS LPDLHPKGEY PPDLFSVEER RQGWVVLHVF GMMYVFVALA IVCDEYFVPA LGVITDKLQI SEDVAGATFM AAGGSAPELF TSLIGVFISH SNVGIGTIVG SAVFNILFVI GTCSLFSREI LNLTWWPLFR DVSFYILDLI MLILFFLDSL IAWWESLLLL LAYAFYVFTM KWNKHIEVWV KEQLSRRPVA KVMALEDLSK PGDGAIAVDE LQDNKKLKLP SLLTRGSSST SLHNSTIRST IYQLMLHSLD PLREVRLAKE KEEESLNQGA RAQPQAKAES KPEEEEPAKL PAVTVTPAPV PDIKGDQKEN PGGQEDVAEA ESTGEMPGEE GETAGEGETE EKSGGETQPE GEGETETQGK GEECEDENEA EGKGDNEGED EGEIHAEDGE MKGNEGETES QELSAENHGE AKNDEKGVED GGGSDGGDSE EEEEEEEEQE EEEEEEEQEE EEEEEEEEEE KGNEEPLSLD WPETRQKQAI YLFLLPIVFP LWLTVPDVRR QESRKFFVFT FLGSIMWIAM FSYLMVWWAH QVGETIGISE EIMGLTILAA GTSIPDLITS VIVARKGLGD MAVSSSVGSN IFDITVGLPV PWLLFSLING LQPVPVSSNG LFCAIVLLFL MLLFVISSIA SCKWRMNKIL GFTMFLLYFV FLIISVMLED RIISCPVSV //