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Protein

Sodium/potassium/calcium exchanger 4

Gene

SLC24A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiport, Calcium transport, Ion transport, Olfaction, Potassium transport, Sensory transduction, Sodium transport, Symport, Transport

Keywords - Ligandi

Calcium, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-425561. Sodium/Calcium exchangers.

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

HGNCiHGNC:10978. SLC24A4.

Subcellular locationi

  • Cytoplasm By similarity
  • Cell membrane By similarity; Multi-pass membrane protein By similarity

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

GO - Cellular componenti

Complete GO annotation...

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 rs587777537dbSNPEnsembl.1
Natural variantiVAR_070183499S → C in AI2A5; autosomal recessive. 1 PublicationCorresponds to variant rs587777536dbSNPEnsembl.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...)Sequence analysis1
Glycosylationi76N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8NFF2.
PaxDbiQ8NFF2.
PeptideAtlasiQ8NFF2.
PRIDEiQ8NFF2.

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.
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.
OMAiSPFSMPE.
OrthoDBiEOG091G0M5C.
PhylomeDBiQ8NFF2.
TreeFamiTF318759.

Family and domain databases

InterProiIPR004481. K/Na/Ca-exchanger.
IPR004837. NaCa_Exmemb.
IPR030232. SLC24A4.
[Graphical view]
PANTHERiPTHR10846. PTHR10846. 1 hit.
PTHR10846:SF21. PTHR10846:SF21. 1 hit.
PfamiPF01699. Na_Ca_ex. 2 hits.
[Graphical view]
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 rs587777537dbSNPEnsembl.1
Natural variantiVAR_070183499S → C in AI2A5; autosomal recessive. 1 PublicationCorresponds to variant rs587777536dbSNPEnsembl.1
Natural variantiVAR_042664613V → I.Corresponds to variant rs4900130dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8NFF2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000431840.

Protein family/group databases

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

PTM databases

iPTMnetiQ8NFF2.
PhosphoSitePlusiQ8NFF2.

Polymorphism and mutation databases

BioMutaiSLC24A4.
DMDMi341941166.

Proteomic databases

EPDiQ8NFF2.
PaxDbiQ8NFF2.
PeptideAtlasiQ8NFF2.
PRIDEiQ8NFF2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi123041.
DisGeNETi123041.
GeneCardsiSLC24A4.
HGNCiHGNC:10978. SLC24A4.
MalaCardsiSLC24A4.
MIMi210750. phenotype.
609840. gene.
615887. phenotype.
neXtProtiNX_Q8NFF2.
OpenTargetsiENSG00000140090.
Orphaneti100032. Hypocalcified amelogenesis imperfecta.
100033. Hypomaturation amelogenesis imperfecta.
PharmGKBiPA35854.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1307. Eukaryota.
ENOG410Y9YY. LUCA.
GeneTreeiENSGT00760000119209.
HOVERGENiHBG054881.
InParanoidiQ8NFF2.
KOiK13752.
OMAiSPFSMPE.
OrthoDBiEOG091G0M5C.
PhylomeDBiQ8NFF2.
TreeFamiTF318759.

Enzyme and pathway databases

ReactomeiR-HSA-425561. Sodium/Calcium exchangers.

Miscellaneous databases

GenomeRNAii123041.
PROiQ8NFF2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140090.
CleanExiHS_SLC24A4.
ExpressionAtlasiQ8NFF2. baseline and differential.
GenevisibleiQ8NFF2. HS.

Family and domain databases

InterProiIPR004481. K/Na/Ca-exchanger.
IPR004837. NaCa_Exmemb.
IPR030232. SLC24A4.
[Graphical view]
PANTHERiPTHR10846. PTHR10846. 1 hit.
PTHR10846:SF21. PTHR10846:SF21. 1 hit.
PfamiPF01699. Na_Ca_ex. 2 hits.
[Graphical view]
TIGRFAMsiTIGR00367. TIGR00367. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNCKX4_HUMAN
AccessioniPrimary (citable) accession number: Q8NFF2
Secondary accession number(s): B4DHE7
, B9ZVY2, Q8N8U6, Q8NCX1, Q8NFF0, Q8NFF1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 133 of the entry and version 2 of the sequence. [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

Caution

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.