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O60721 (NCKX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/potassium/calcium exchanger 1
Alternative name(s):
Na(+)/K(+)/Ca(2+)-exchange protein 1
Retinal rod Na-Ca+K exchanger
Solute carrier family 24 member 1
Gene names
Name:SLC24A1
Synonyms:KIAA0702, NCKX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1099 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Night blindness, congenital stationary, 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 processAntiport
Calcium transport
Ion transport
Sensory transduction
Symport
Transport
Vision
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCongenital stationary night blindness
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion transport

Non-traceable author statement PubMed 7539424. Source: UniProtKB

ion transport

Traceable author statement. Source: Reactome

phototransduction, visible light

Traceable author statement. Source: Reactome

response to light intensity

Non-traceable author statement Ref.1. Source: UniProtKB

rhodopsin mediated signaling pathway

Traceable author statement. Source: Reactome

sodium ion transmembrane transport

Non-traceable author statement Ref.2. Source: GOC

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.2. Source: ProtInc

visual perception

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.2. Source: ProtInc

membrane

Traceable author statement Ref.2. Source: ProtInc

outer membrane

Non-traceable author statement Ref.1. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium, 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

NCK1P163333EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10991099Sodium/potassium/calcium exchanger 1
PRO_0000223303
Signal peptide1 – ?Not cleaved

Regions

Topological domain1 – 452452Extracellular Potential
Transmembrane453 – 47321Helical; Potential
Topological domain474 – 49724Cytoplasmic Potential
Transmembrane498 – 51821Helical; Potential
Topological domain519 – 5224Extracellular Potential
Transmembrane523 – 54321Helical; Potential
Topological domain544 – 56320Cytoplasmic Potential
Transmembrane564 – 58421Helical; Potential
Topological domain5851Extracellular Potential
Transmembrane586 – 60621Helical; Potential
Topological domain607 – 907301Cytoplasmic Potential
Transmembrane908 – 92821Helical; Potential
Topological domain929 – 9357Extracellular Potential
Transmembrane936 – 95621Helical; Potential
Topological domain957 – 97115Cytoplasmic Potential
Transmembrane972 – 99221Helical; Potential
Topological domain993 – 101018Extracellular Potential
Transmembrane1011 – 103121Helical; Potential
Topological domain1032 – 10398Cytoplasmic Potential
Transmembrane1040 – 106021Helical; Potential
Topological domain1061 – 10688Extracellular Potential
Transmembrane1069 – 108921Helical; Potential
Topological domain1090 – 109910Cytoplasmic Potential
Repeat494 – 53441Alpha-1
Repeat979 – 101032Alpha-2
Compositional bias860 – 89031Poly-Glu

Amino acid modifications

Modified residue6581Phosphoserine Potential
Modified residue7241Phosphothreonine Ref.5
Modified residue7261Phosphothreonine Ref.5
Glycosylation2901N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence631 – 64818Missing in isoform 2.
VSP_006160
Natural variant371T → S.
Corresponds to variant rs3743171 [ dbSNP | Ensembl ].
VAR_050221
Natural variant3111V → L.
Corresponds to variant rs34363823 [ dbSNP | Ensembl ].
VAR_050222
Natural variant3131L → V.
Corresponds to variant rs35571449 [ dbSNP | Ensembl ].
VAR_050223

Experimental info

Sequence conflict5161V → I in AAB97832. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 3911856BB088B5FD

FASTA1,099121,374
        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 

« Hide

Isoform 2 [UniParc].

Checksum: A72589F54E4C05B3
Show »

FASTA1,081119,481

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.
RefSeqNP_004718.1. NM_004727.2.
XP_005254835.1. XM_005254778.2.
XP_005254836.1. XM_005254779.2.
UniGeneHs.173092.

3D structure databases

ProteinModelPortalO60721.
SMRO60721. Positions 475-602, 909-1087.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114624. 2 interactions.
IntActO60721. 5 interactions.
STRING9606.ENSP00000261892.

Protein family/group databases

TCDB2.A.19.4.9. the ca(2+):cation antiporter (caca) family.

PTM databases

PhosphoSiteO60721.

Proteomic databases

PaxDbO60721.
PRIDEO60721.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261892; ENSP00000261892; ENSG00000074621. [O60721-1]
ENST00000339868; ENSP00000341837; ENSG00000074621. [O60721-2]
ENST00000546330; ENSP00000439190; ENSG00000074621. [O60721-2]
GeneID9187.
KEGGhsa:9187.
UCSCuc010ujf.2. human. [O60721-1]
uc010ujh.2. human. [O60721-2]

Organism-specific databases

CTD9187.
GeneCardsGC15P065914.
HGNCHGNC:10975. SLC24A1.
HPAHPA039370.
MIM603617. gene.
613830. phenotype.
neXtProtNX_O60721.
Orphanet215. Congenital stationary night blindness.
PharmGKBPA35851.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0530.
HOGENOMHOG000231933.
HOVERGENHBG104097.
InParanoidO60721.
KOK13749.
OMAKGEYPPD.
PhylomeDBO60721.
TreeFamTF318759.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressO60721.
BgeeO60721.
CleanExHS_SLC24A1.
GenevestigatorO60721.

Family and domain databases

InterProIPR004817. K-dep_Na/Ca-exchanger.
IPR004481. K/Na/Ca-exchanger.
IPR004837. NaCa_Exmemb.
[Graphical view]
PANTHERPTHR10846. PTHR10846. 1 hit.
PTHR10846:SF7. PTHR10846:SF7. 1 hit.
PfamPF01699. Na_Ca_ex. 2 hits.
[Graphical view]
TIGRFAMsTIGR00927. 2A1904. 1 hit.
TIGR00367. TIGR00367. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi9187.
NextBio34449.
PROO60721.
SOURCESearch...

Entry information

Entry nameNCKX1_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM