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Protein

Sodium/potassium/calcium exchanger 4

Gene

SLC24A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transports 1 Ca2+ and 1 K+ in exchange for 4 Na+. Controls the rapid response termination and proper regulation of adaptation in olfactory sensory neurons (OSNs) which subsequently influences how odor information is encoded and perceived. May play a role in calcium transport during amelogenesis (By similarity).By similarity

Caution

It is uncertain whether Met-1 or Met-18 is the initiator.Curated

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAntiport, Calcium transport, Ion transport, Olfaction, Potassium transport, Sensory transduction, Sodium transport, Symport, Transport
LigandCalcium, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-425561 Sodium/Calcium exchangers
R-HSA-5619055 Defective SLC24A4 causes hypomineralized amelogenesis imperfecta (AI)

Protein family/group databases

TCDBi2.A.19.4.5 the ca(2+):cation antiporter (caca) family

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/potassium/calcium exchanger 4
Alternative name(s):
Na(+)/K(+)/Ca(2+)-exchange protein 4
Solute carrier family 24 member 4
Gene namesi
Name:SLC24A4Imported
Synonyms:NCKX4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000140090.17
HGNCiHGNC:10978 SLC24A4
MIMi609840 gene
neXtProtiNX_Q8NFF2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini39 – 97ExtracellularCuratedAdd BLAST59
Transmembranei98 – 118HelicalSequence analysisAdd BLAST21
Topological domaini119 – 142CytoplasmicCuratedAdd BLAST24
Transmembranei143 – 163HelicalSequence analysisAdd BLAST21
Topological domaini164 – 172ExtracellularCurated9
Transmembranei173 – 193HelicalSequence analysisAdd BLAST21
Topological domaini194 – 200CytoplasmicCurated7
Transmembranei201 – 221HelicalSequence analysisAdd BLAST21
Topological domaini222 – 224ExtracellularCurated3
Transmembranei225 – 245HelicalSequence analysisAdd BLAST21
Topological domaini246 – 457CytoplasmicCuratedAdd BLAST212
Transmembranei458 – 478HelicalSequence analysisAdd BLAST21
Topological domaini479ExtracellularCurated1
Transmembranei480 – 500HelicalSequence analysisAdd BLAST21
Topological domaini501 – 526CytoplasmicCuratedAdd BLAST26
Transmembranei527 – 547HelicalSequence analysisAdd BLAST21
Topological domaini548 – 557ExtracellularCurated10
Transmembranei558 – 578HelicalSequence analysisAdd BLAST21
Topological domaini579 – 586CytoplasmicCurated8
Transmembranei587 – 607HelicalSequence analysisAdd BLAST21
Topological domaini608 – 622ExtracellularCuratedAdd BLAST15

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Amelogenesis imperfecta, hypomaturation type, 2A5 (AI2A5)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.
See also OMIM:615887
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071475146A → V in AI2A5; autosomal recessive. 1 PublicationCorresponds to variant dbSNP:rs587777537Ensembl.1
Natural variantiVAR_070183499S → C in AI2A5; autosomal recessive. 1 PublicationCorresponds to variant dbSNP:rs587777536Ensembl.1

Keywords - Diseasei

Amelogenesis imperfecta, Disease mutation

Organism-specific databases

DisGeNETi123041
MalaCardsiSLC24A4
MIMi210750 phenotype
615887 phenotype
OpenTargetsiENSG00000140090
Orphaneti100032 Hypocalcified amelogenesis imperfecta
100033 Hypomaturation amelogenesis imperfecta
PharmGKBiPA35854

Polymorphism and mutation databases

BioMutaiSLC24A4
DMDMi341941166

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 38Sequence analysisAdd BLAST38
ChainiPRO_000001937339 – 622Sodium/potassium/calcium exchanger 4Add BLAST584

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi69N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi76N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8NFF2
PaxDbiQ8NFF2
PeptideAtlasiQ8NFF2
PRIDEiQ8NFF2
ProteomicsDBi73293
73294 [Q8NFF2-2]
73295 [Q8NFF2-3]
73296 [Q8NFF2-4]

PTM databases

iPTMnetiQ8NFF2
PhosphoSitePlusiQ8NFF2

Expressioni

Tissue specificityi

Expressed abundantly in all regions of the brain, aorta, lung and thymus. Expressed at lower levels in the stomach and intestine.

Gene expression databases

BgeeiENSG00000140090
CleanExiHS_SLC24A4
ExpressionAtlasiQ8NFF2 baseline and differential
GenevisibleiQ8NFF2 HS

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000431840

Structurei

3D structure databases

ProteinModelPortaliQ8NFF2
SMRiQ8NFF2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati139 – 179Alpha-1Add BLAST41
Repeati495 – 526Alpha-2Add BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi395 – 406Poly-ProAdd BLAST12

Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1307 Eukaryota
ENOG410Y9YY LUCA
GeneTreeiENSGT00760000119209
HOVERGENiHBG054881
InParanoidiQ8NFF2
KOiK13752
OMAiWRNRKLM
OrthoDBiEOG091G0M5C
PhylomeDBiQ8NFF2
TreeFamiTF318759

Family and domain databases

InterProiView protein in InterPro
IPR004481 K/Na/Ca-exchanger
IPR004837 NaCa_Exmemb
IPR030232 SLC24A4
PANTHERiPTHR10846 PTHR10846, 1 hit
PTHR10846:SF21 PTHR10846:SF21, 1 hit
PfamiView protein in Pfam
PF01699 Na_Ca_ex, 2 hits
TIGRFAMsiTIGR00367 TIGR00367, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NFF2-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MALRGTLRPL KVRRRREMLP QQVGFVCAVL ALVCCASGLF GSLGHKTASA
60 70 80 90 100
SKRVLPDTWR NRKLMAPVNG TQTAKNCTDP AIHEFPTDLF SNKERQHGAV
110 120 130 140 150
LLHILGALYM FYALAIVCDD FFVPSLEKIC ERLHLSEDVA GATFMAAGSS
160 170 180 190 200
TPELFASVIG VFITHGDVGV GTIVGSAVFN ILCIIGVCGL FAGQVVRLTW
210 220 230 240 250
WAVCRDSVYY TISVIVLIVF IYDEQIVWWE GLVLIILYVF YILIMKYNVK
260 270 280 290 300
MQAFFTVKQK SIANGNPVNS ELEAGNDFYD GSYDDPSVPL LGQVKEKPQY
310 320 330 340 350
GKNPVVMVDE IMSSSPPKFT FPEAGLRIMI TNKFGPRTRL RMASRIIINE
360 370 380 390 400
RQRLINSANG VSSKPLQNGR HENIENGNVP VENPEDPQQN QEQQPPPQPP
410 420 430 440 450
PPEPEPVEAD FLSPFSVPEA RGDKVKWVFT WPLIFLLCVT IPNCSKPRWE
460 470 480 490 500
KFFMVTFITA TLWIAVFSYI MVWLVTIIGY TLGIPDVIMG ITFLAAGTSV
510 520 530 540 550
PDCMASLIVA RQGLGDMAVS NTIGSNVFDI LVGLGVPWGL QTMVVNYGST
560 570 580 590 600
VKINSRGLVY SVVLLLGSVA LTVLGIHLNK WRLDRKLGVY VLVLYAIFLC
610 620
FSIMIEFNVF TFVNLPMCRE DD
Length:622
Mass (Da):69,042
Last modified:July 27, 2011 - v2
Checksum:i00D69370E55EE388
GO
Isoform 2 (identifier: Q8NFF2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-64: Missing.

Show »
Length:558
Mass (Da):61,938
Checksum:i3DC0E1DFBC5D7828
GO
Isoform 3 (identifier: Q8NFF2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     275-293: Missing.

Show »
Length:603
Mass (Da):67,001
Checksum:iC8A7D3637BF861F8
GO
Isoform 4 (identifier: Q8NFF2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-109: Missing.
     172-210: Missing.

Note: No experimental confirmation available.
Show »
Length:474
Mass (Da):52,760
Checksum:i5C9395536A220F7A
GO

Sequence cautioni

The sequence AAH69653 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAM76070 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAM76071 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC04715 differs from that shown. Probable cloning artifact.Curated
The sequence CAD38903 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti444C → S in BAC04715 (PubMed:14702039).Curated1
Sequence conflicti560Y → H in BAG58108 (PubMed:14702039).Curated1

Polymorphismi

Genetic variants in SLC24A4 define the skin/hair/eye pigmentation variation locus 6 (SHEP6) [MIMi:210750]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071475146A → V in AI2A5; autosomal recessive. 1 PublicationCorresponds to variant dbSNP:rs587777537Ensembl.1
Natural variantiVAR_070183499S → C in AI2A5; autosomal recessive. 1 PublicationCorresponds to variant dbSNP:rs587777536Ensembl.1
Natural variantiVAR_042664613V → I. Corresponds to variant dbSNP:rs4900130Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0083701 – 109Missing in isoform 4. 1 PublicationAdd BLAST109
Alternative sequenceiVSP_0083691 – 64Missing in isoform 2. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_008371172 – 210Missing in isoform 4. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_008372275 – 293Missing in isoform 3. 2 PublicationsAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF520704 mRNA Translation: AAM76070.1 Different initiation.
AF520705 mRNA Translation: AAM76071.1 Different initiation.
AF520706 mRNA Translation: AAM76072.1
AK096171 mRNA Translation: BAC04715.1 Sequence problems.
AK295059 mRNA Translation: BAG58108.1
AL118559 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW81485.1
BC069653 mRNA Translation: AAH69653.1 Different initiation.
AL834225 mRNA Translation: CAD38903.1 Different initiation.
CCDSiCCDS45155.2 [Q8NFF2-3]
CCDS45156.1 [Q8NFF2-2]
CCDS9903.2 [Q8NFF2-1]
RefSeqiNP_705932.2, NM_153646.3 [Q8NFF2-1]
NP_705933.2, NM_153647.3 [Q8NFF2-3]
NP_705934.1, NM_153648.3 [Q8NFF2-2]
XP_011534743.1, XM_011536441.2
XP_011534744.1, XM_011536442.2
UniGeneiHs.385530

Genome annotation databases

EnsembliENST00000393265; ENSP00000376948; ENSG00000140090 [Q8NFF2-2]
ENST00000531433; ENSP00000433302; ENSG00000140090 [Q8NFF2-3]
ENST00000532405; ENSP00000431840; ENSG00000140090 [Q8NFF2-1]
GeneIDi123041
KEGGihsa:123041
UCSCiuc001yai.4 human [Q8NFF2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNCKX4_HUMAN
AccessioniPrimary (citable) accession number: Q8NFF2
Secondary accession number(s): B4DHE7
, B9ZVY2, Q8N8U6, Q8NCX1, Q8NFF0, Q8NFF1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 143 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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