O60721 (NCKX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/potassium/calcium exchanger 1

Alternative name(s):
Na(+)/K(+)/Ca(2+)-exchange protein 1
Retinal rod Na-Ca+K exchanger

Gene names

Name:	SLC24A1
Synonyms:	KIAA0702, NCKX1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1099 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Critical component of the visual transduction cascade, controlling the calcium concentration of outer segments during light and darkness. Light causes a rapid lowering of cytosolic free calcium in the outer segment of both retinal rod and cone photoreceptors and the light-induced lowering of calcium is caused by extrusion via this protein which plays a key role in the process of light adaptation. Transports 1 Ca2+ and 1 K+ in exchange for 4 Na+. Ref.4
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in the retina, particularly in the inner segment, outer and inner nuclear layers, and ganglion cell layer. Ref.6
Post-translational modification	The uncleaved signal sequence is required for efficient membrane targeting and proper membrane integration.
Involvement in disease	Congenital stationary night blindness 1D (CSNB1D) [MIM:613830]: An autosomal recessive form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision. CSNB1D is characterized by a Riggs type of electroretinogram (proportionally reduced a- and b-waves). Patients have visual acuity within the normal range and no symptoms of myopia and/or nystagmus. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the sodium/potassium/calcium exchanger family. SLC24A subfamily.

Ontologies

Keywords
Biological process	Antiport Calcium transport Ion transport Sensory transduction Symport Transport Vision
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Congenital stationary night blindness
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	response to light intensity Non-traceable author statement Ref.1. Source: UniProtKB visual perception Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc outer membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	calcium, potassium:sodium antiporter activity Non-traceable author statement Ref.2. Source: UniProtKB symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	3	EBI-1753504,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60721-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O60721-2)

The sequence of this isoform differs from the canonical sequence as follows:
     631-648: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1099	1099	Sodium/potassium/calcium exchanger 1		PRO_0000223303
	Signal peptide	1 – ?		Not cleaved
Regions
	Topological domain	1 – 452	452	Extracellular Potential
	Transmembrane	453 – 473	21	Helical; Potential
	Topological domain	474 – 497	24	Cytoplasmic Potential
	Transmembrane	498 – 518	21	Helical; Potential
	Topological domain	519 – 522	4	Extracellular Potential
	Transmembrane	523 – 543	21	Helical; Potential
	Topological domain	544 – 563	20	Cytoplasmic Potential
	Transmembrane	564 – 584	21	Helical; Potential
	Topological domain	585	1	Extracellular Potential
	Transmembrane	586 – 606	21	Helical; Potential
	Topological domain	607 – 907	301	Cytoplasmic Potential
	Transmembrane	908 – 928	21	Helical; Potential
	Topological domain	929 – 935	7	Extracellular Potential
	Transmembrane	936 – 956	21	Helical; Potential
	Topological domain	957 – 971	15	Cytoplasmic Potential
	Transmembrane	972 – 992	21	Helical; Potential
	Topological domain	993 – 1010	18	Extracellular Potential
	Transmembrane	1011 – 1031	21	Helical; Potential
	Topological domain	1032 – 1039	8	Cytoplasmic Potential
	Transmembrane	1040 – 1060	21	Helical; Potential
	Topological domain	1061 – 1068	8	Extracellular Potential
	Transmembrane	1069 – 1089	21	Helical; Potential
	Topological domain	1090 – 1099	10	Cytoplasmic Potential
	Repeat	494 – 534	41	Alpha-1
	Repeat	979 – 1010	32	Alpha-2
	Compositional bias	860 – 890	31	Poly-Glu
Amino acid modifications
	Modified residue	658	1	Phosphoserine Potential
	Modified residue	724	1	Phosphothreonine Ref.5
	Modified residue	726	1	Phosphothreonine Ref.5
	Glycosylation	290	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	631 – 648	18	Missing in isoform 2.		VSP_006160
	Natural variant	37	1	T → S. Corresponds to variant rs3743171 [ dbSNP | Ensembl ].		VAR_050221
	Natural variant	311	1	V → L. Corresponds to variant rs34363823 [ dbSNP | Ensembl ].		VAR_050222
	Natural variant	313	1	L → V. Corresponds to variant rs35571449 [ dbSNP | Ensembl ].		VAR_050223
Experimental info
	Sequence conflict	516	1	V → I in AAB97832. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 3911856BB088B5FD	FASTA	1,099	121,374
	10 20 30 40 50 60 MGKLIRMGPQ ERWLLRTKRL HWSRLLFLLG MLIIGSTYQH LRRPRGLSSL WAAVSSHQPI 70 80 90 100 110 120 KLASRDLSSE EMMMMSSSPS KPSSEMGGKM LVPQASVGSD EATLSMTVEN IPSMPKRTAK 130 140 150 160 170 180 MIPTTTKNNY SPTAAGTERR KEDTPTSSRT LTYYTSTSSR QIVKKYTPTP RGEMKSYSPT 190 200 210 220 230 240 QVREKVKYTP SPRGRRVGTY VPSTFMTMET SHAITPRTTV KDSDITATYK ILETNSLKRI 250 260 270 280 290 300 MEETTPTTLK GMFDSTPTFL THEVEANVLT SPRSVMEKNN LFPPRRVESN SSAHPWGLVG 310 320 330 340 350 360 KSNPKTPQGT VLLHTPATSE GQVTISTMTG SSPAETKAFT AAWSLRNPSP RTSVSAIKTA 370 380 390 400 410 420 PAIVWRLAKK PSTAPSTSTT PTVRAKLTMQ VHHCVVVKPT PAMLTTPSPS LTTALLPEEL 430 440 450 460 470 480 SPSPSVLPPS LPDLHPKGEY PPDLFSVEER RQGWVVLHVF GMMYVFVALA IVCDEYFVPA 490 500 510 520 530 540 LGVITDKLQI SEDVAGATFM AAGGSAPELF TSLIGVFISH SNVGIGTIVG SAVFNILFVI 550 560 570 580 590 600 GTCSLFSREI LNLTWWPLFR DVSFYILDLI MLILFFLDSL IAWWESLLLL LAYAFYVFTM 610 620 630 640 650 660 KWNKHIEVWV KEQLSRRPVA KVMALEDLSK PGDGAIAVDE LQDNKKLKLP SLLTRGSSST 670 680 690 700 710 720 SLHNSTIRST IYQLMLHSLD PLREVRLAKE KEEESLNQGA RAQPQAKAES KPEEEEPAKL 730 740 750 760 770 780 PAVTVTPAPV PDIKGDQKEN PGGQEDVAEA ESTGEMPGEE GETAGEGETE EKSGGETQPE 790 800 810 820 830 840 GEGETETQGK GEECEDENEA EGKGDNEGED EGEIHAEDGE MKGNEGETES QELSAENHGE 850 860 870 880 890 900 AKNDEKGVED GGGSDGGDSE EEEEEEEEQE EEEEEEEQEE EEEEEEEEEE KGNEEPLSLD 910 920 930 940 950 960 WPETRQKQAI YLFLLPIVFP LWLTVPDVRR QESRKFFVFT FLGSIMWIAM FSYLMVWWAH 970 980 990 1000 1010 1020 QVGETIGISE EIMGLTILAA GTSIPDLITS VIVARKGLGD MAVSSSVGSN IFDITVGLPV 1030 1040 1050 1060 1070 1080 PWLLFSLING LQPVPVSSNG LFCAIVLLFL MLLFVISSIA SCKWRMNKIL GFTMFLLYFV 1090 FLIISVMLED RIISCPVSV
	Isoform 2 [UniParc]. Checksum: A72589F54E4C05B3	FASTA	1,081	119,481
	10 20 30 40 50 60 MGKLIRMGPQ ERWLLRTKRL HWSRLLFLLG MLIIGSTYQH LRRPRGLSSL WAAVSSHQPI 70 80 90 100 110 120 KLASRDLSSE EMMMMSSSPS KPSSEMGGKM LVPQASVGSD EATLSMTVEN IPSMPKRTAK 130 140 150 160 170 180 MIPTTTKNNY SPTAAGTERR KEDTPTSSRT LTYYTSTSSR QIVKKYTPTP RGEMKSYSPT 190 200 210 220 230 240 QVREKVKYTP SPRGRRVGTY VPSTFMTMET SHAITPRTTV KDSDITATYK ILETNSLKRI 250 260 270 280 290 300 MEETTPTTLK GMFDSTPTFL THEVEANVLT SPRSVMEKNN LFPPRRVESN SSAHPWGLVG 310 320 330 340 350 360 KSNPKTPQGT VLLHTPATSE GQVTISTMTG SSPAETKAFT AAWSLRNPSP RTSVSAIKTA 370 380 390 400 410 420 PAIVWRLAKK PSTAPSTSTT PTVRAKLTMQ VHHCVVVKPT PAMLTTPSPS LTTALLPEEL 430 440 450 460 470 480 SPSPSVLPPS LPDLHPKGEY PPDLFSVEER RQGWVVLHVF GMMYVFVALA IVCDEYFVPA 490 500 510 520 530 540 LGVITDKLQI SEDVAGATFM AAGGSAPELF TSLIGVFISH SNVGIGTIVG SAVFNILFVI 550 560 570 580 590 600 GTCSLFSREI LNLTWWPLFR DVSFYILDLI MLILFFLDSL IAWWESLLLL LAYAFYVFTM 610 620 630 640 650 660 KWNKHIEVWV KEQLSRRPVA KVMALEDLSK LPSLLTRGSS STSLHNSTIR STIYQLMLHS 670 680 690 700 710 720 LDPLREVRLA KEKEEESLNQ GARAQPQAKA ESKPEEEEPA KLPAVTVTPA PVPDIKGDQK 730 740 750 760 770 780 ENPGGQEDVA EAESTGEMPG EEGETAGEGE TEEKSGGETQ PEGEGETETQ GKGEECEDEN 790 800 810 820 830 840 EAEGKGDNEG EDEGEIHAED GEMKGNEGET ESQELSAENH GEAKNDEKGV EDGGGSDGGD 850 860 870 880 890 900 SEEEEEEEEE QEEEEEEEEQ EEEEEEEEEE EEKGNEEPLS LDWPETRQKQ AIYLFLLPIV 910 920 930 940 950 960 FPLWLTVPDV RRQESRKFFV FTFLGSIMWI AMFSYLMVWW AHQVGETIGI SEEIMGLTIL 970 980 990 1000 1010 1020 AAGTSIPDLI TSVIVARKGL GDMAVSSSVG SNIFDITVGL PVPWLLFSLI NGLQPVPVSS 1030 1040 1050 1060 1070 1080 NGLFCAIVLL FLMLLFVISS IASCKWRMNK ILGFTMFLLY FVFLIISVML EDRIISCPVS V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Chromosomal localization and genomic organization of the human retinal rod Na-Ca+K exchanger." Tucker J.E., Winkfein R.J., Murthy S.K., Friedman J.S., Walter M.A., Demetrick D.J., Schnetkamp P.P.M. Hum. Genet. 103:411-414(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Retina.
[2]	"cDNA cloning of the human retinal rod Na-Ca + K exchanger: comparison with a revised bovine sequence." Tucker J.E., Winkfein R.J., Cooper C.B., Schnetkamp P.P.M. Invest. Ophthalmol. Vis. Sci. 39:435-440(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Retina.
[3]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1003 (ISOFORM 2). Tissue: Brain.
[4]	"The retinal rod Na(+)/Ca(2+),K(+) exchanger contains a noncleaved signal sequence required for translocation of the N-terminus." McKiernan C.J., Friedlander M. J. Biol. Chem. 274:38177-38182(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE N-TERMINUS IN TARGETING.
[5]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-724 AND THR-726, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[6]	"A mutation in SLC24A1 implicated in autosomal-recessive congenital stationary night blindness." Riazuddin S.A., Shahzadi A., Zeitz C., Ahmed Z.M., Ayyagari R., Chavali V.R., Ponferrada V.G., Audo I., Michiels C., Lancelot M.E., Nasir I.A., Zafar A.U., Khan S.N., Husnain T., Jiao X., MacDonald I.M., Riazuddin S., Sieving P.A., Katsanis N., Hejtmancik J.F. Am. J. Hum. Genet. 87:523-531(2010) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN CSNB1D.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF062921 mRNA. Translation: AAC16732.1. AF062922 mRNA. Translation: AAC77912.1. AF026132 mRNA. Translation: AAB97832.1. AB014602 mRNA. Translation: BAA31677.2. Sequence problems.
IPI	IPI00006195. IPI00216460.
RefSeq	NP_004718.1. NM_004727.2.
UniGene	Hs.173092.
3D structure databases
ProteinModelPortal	O60721.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60721. 5 interactions.
MINT	MINT-7241544.
STRING	9606.ENSP00000261892.
PTM databases
PhosphoSite	O60721.
Proteomic databases
PaxDb	O60721.
PRIDE	O60721.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261892; ENSP00000261892; ENSG00000074621. ENST00000339868; ENSP00000341837; ENSG00000074621. ENST00000546330; ENSP00000439190; ENSG00000074621.
GeneID	9187.
KEGG	hsa:9187.
UCSC	uc010ujf.2. human. uc010ujh.2. human.
Organism-specific databases
CTD	9187.
GeneCards	GC15P065914.
HGNC	HGNC:10975. SLC24A1.
HPA	HPA039370.
MIM	603617. gene. 613830. phenotype.
neXtProt	NX_O60721.
Orphanet	215. Congenital stationary night blindness.
PharmGKB	PA35851.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0530.
HOGENOM	HOG000231933.
HOVERGEN	HBG104097.
InParanoid	O60721.
KO	K13749.
OMA	MTVENIP.
Enzyme and pathway databases
Pathway_Interaction_DB	rhodopsin_pathway. Visual signal transduction: Rods.
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O60721.
Bgee	O60721.
CleanEx	HS_SLC24A1.
Genevestigator	O60721.
GermOnline	ENSG00000074621. Homo sapiens.
Family and domain databases
InterPro	IPR004817. K-dep_Na/Ca-exchanger. IPR004481. K/Na/Ca-exchanger. IPR004837. NaCa_Exmemb. [Graphical view]
PANTHER	PTHR10846. PTHR10846. 1 hit. PTHR10846:SF7. PTHR10846:SF7. 1 hit.
Pfam	PF01699. Na_Ca_ex. 2 hits. [Graphical view]
TIGRFAMs	TIGR00927. 2A1904. 1 hit. TIGR00367. TIGR00367. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	9187.
NextBio	34449.
SOURCE	Search...

Entry information

Entry name

NCKX1_HUMAN

Accession

Primary (citable) accession number: O60721
Secondary accession number(s): O43485, O75184

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2001
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.