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Protein

Sodium/hydrogen exchanger 4

Gene

SLC9A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. May play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage. Is relatively amiloride and ethylisopropylamiloride (EIPA) insensitive. Can be activated under conditions of hyperosmolar-induced cell shrinkage in a sustained intracellular acidification-dependence manner. Activated by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a sustained intracellular acidification-dependence manner. Affects potassium/proton exchange as well as sodium/proton and lithium/proton exchange. In basolateral cell membrane, participates in homeostatic control of intracellular pH, and may play a role in proton extrusion in order to achieve transepithelial HCO3- secretion. In apical cell membrane may be involved in mediating sodium absorption. Requires for normal levels of gastric acid secretion, secretory membrane development, parietal cell maturation and/or differentiation and at least secondarily for chief cell differentiation (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiR-HSA-425986. Sodium/Proton exchangers.

Protein family/group databases

TCDBi2.A.36.1.18. the monovalent cation:proton antiporter-1 (cpa1) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/hydrogen exchanger 4
Alternative name(s):
Na(+)/H(+) exchanger 4
Short name:
NHE-4
Solute carrier family 9 member 4
Gene namesi
Name:SLC9A4
Synonyms:NHE4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11077. SLC9A4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 13CytoplasmicSequence analysisAdd BLAST13
Intramembranei14 – 28Name=A/M1Sequence analysisAdd BLAST15
Topological domaini29 – 69CytoplasmicSequence analysisAdd BLAST41
Intramembranei70 – 90Name=B/M2Sequence analysisAdd BLAST21
Topological domaini91 – 94CytoplasmicSequence analysis4
Transmembranei95 – 115Helical; Name=C/M3Sequence analysisAdd BLAST21
Topological domaini116 – 127ExtracellularSequence analysisAdd BLAST12
Transmembranei128 – 148Helical; Name=D/M4Sequence analysisAdd BLAST21
Topological domaini149 – 154CytoplasmicSequence analysis6
Transmembranei155 – 175Helical; Name=E/M5Sequence analysisAdd BLAST21
Topological domaini176 – 196ExtracellularSequence analysisAdd BLAST21
Transmembranei197 – 217Helical; Name=F/M5ASequence analysisAdd BLAST21
Topological domaini218 – 226CytoplasmicSequence analysis9
Transmembranei227 – 247Helical; Name=G/M5BSequence analysisAdd BLAST21
Topological domaini248 – 270ExtracellularSequence analysisAdd BLAST23
Transmembranei271 – 291Helical; Name=H/M6Sequence analysisAdd BLAST21
Topological domaini292 – 304CytoplasmicSequence analysisAdd BLAST13
Transmembranei305 – 325Helical; Name=I/M7Sequence analysisAdd BLAST21
Topological domaini326 – 356ExtracellularSequence analysisAdd BLAST31
Transmembranei357 – 373Helical; Name=J/M8Sequence analysisAdd BLAST17
Topological domaini374 – 384CytoplasmicSequence analysisAdd BLAST11
Transmembranei385 – 405Helical; Name=K/M9Sequence analysisAdd BLAST21
Topological domaini406 – 420ExtracellularSequence analysisAdd BLAST15
Intramembranei421 – 441Name=LSequence analysisAdd BLAST21
Topological domaini442 – 450ExtracellularSequence analysis9
Transmembranei451 – 471Helical; Name=M/M10Sequence analysisAdd BLAST21
Topological domaini472 – 798CytoplasmicSequence analysisAdd BLAST327

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi389015.
OpenTargetsiENSG00000180251.
PharmGKBiPA35933.

Polymorphism and mutation databases

BioMutaiSLC9A4.
DMDMi296452906.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003146651 – 798Sodium/hydrogen exchanger 4Add BLAST798

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi342N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

May be phosphorylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ6AI14.
PeptideAtlasiQ6AI14.
PRIDEiQ6AI14.

PTM databases

iPTMnetiQ6AI14.
PhosphoSitePlusiQ6AI14.

Expressioni

Gene expression databases

BgeeiENSG00000180251.
CleanExiHS_SLC9A4.

Organism-specific databases

HPAiHPA036096.

Interactioni

Subunit structurei

Interacts with CHP1 and CHP2.By similarity

Protein-protein interaction databases

BioGridi132934. 2 interactors.
STRINGi9606.ENSP00000295269.

Structurei

3D structure databases

ProteinModelPortaliQ6AI14.
SMRiQ6AI14.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
GeneTreeiENSGT00760000119074.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiQ6AI14.
KOiK13961.
OMAiLAFCQIW.
OrthoDBiEOG091G02Q0.
PhylomeDBiQ6AI14.
TreeFamiTF317212.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001953. Na/H_exchanger_2.
IPR004709. NaH_exchanger.
IPR032103. NHE_CaM-bd.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 1 hit.
PfamiPF00999. Na_H_Exchanger. 1 hit.
PF16644. NEXCaM_BD. 1 hit.
[Graphical view]
PRINTSiPR01084. NAHEXCHNGR.
PR01086. NAHEXCHNGR2.
TIGRFAMsiTIGR00840. b_cpa1. 1 hit.

Sequencei

Sequence statusi: Complete.

Q6AI14-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALQMFVTYS PWNCLLLLVA LECSEASSDL NESANSTAQY ASNAWFAAAS
60 70 80 90 100
SEPEEGISVF ELDYDYVQIP YEVTLWILLA SLAKIGFHLY HRLPGLMPES
110 120 130 140 150
CLLILVGALV GGIIFGTDHK SPPVMDSSIY FLYLLPPIVL EGGYFMPTRP
160 170 180 190 200
FFENIGSILW WAVLGALINA LGIGLSLYLI CQVKAFGLGD VNLLQNLLFG
210 220 230 240 250
SLISAVDPVA VLAVFEEARV NEQLYMMIFG EALLNDGITV VLYNMLIAFT
260 270 280 290 300
KMHKFEDIET VDILAGCARF IVVGLGGVLF GIVFGFISAF ITRFTQNISA
310 320 330 340 350
IEPLIVFMFS YLSYLAAETL YLSGILAITA CAVTMKKYVE ENVSQTSYTT
360 370 380 390 400
IKYFMKMLSS VSETLIFIFM GVSTVGKNHE WNWAFICFTL AFCQIWRAIS
410 420 430 440 450
VFALFYISNQ FRTFPFSIKD QCIIFYSGVR GAGSFSLAFL LPLSLFPRKK
460 470 480 490 500
MFVTATLVVI YFTVFIQGIT VGPLVRYLDV KKTNKKESIN EELHIRLMDH
510 520 530 540 550
LKAGIEDVCG HWSHYQVRDK FKKFDHRYLR KILIRKNLPK SSIVSLYKKL
560 570 580 590 600
EMKQAIEMVE TGILSSTAFS IPHQAQRIQG IKRLSPEDVE SIRDILTSNM
610 620 630 640 650
YQVRQRTLSY NKYNLKPQTS EKQAKEILIR RQNTLRESMR KGHSLPWGKP
660 670 680 690 700
AGTKNIRYLS YPYGNPQSAG RDTRAAGFSD DDSSDPGSPS ITFSACSRIG
710 720 730 740 750
SLQKQEAQEI IPMKSLHRGR KAFSFGYQRN TSQEEYLGGV RRVALRPKPL
760 770 780 790
FHAVDEEGES GGESEGKASL VEVRSRWTAD HGHGRDHHRS HSPLLQKK
Length:798
Mass (Da):89,814
Last modified:May 18, 2010 - v2
Checksum:i757DAD603ECFF0D3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti429V → A in CAH10500 (PubMed:17974005).Curated1
Sequence conflicti784G → S in CAH10500 (PubMed:17974005).Curated1
Sequence conflicti784G → S in CAH10600 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_056209116G → S.Corresponds to variant rs17027275dbSNPEnsembl.1
Natural variantiVAR_056210581I → V.Corresponds to variant rs6742280dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL833048 mRNA. Translation: CAH10600.1.
CR627411 mRNA. Translation: CAH10500.1.
AC007278 Genomic DNA. No translation available.
CCDSiCCDS33264.1.
RefSeqiNP_001011552.2. NM_001011552.3.
UniGeneiHs.447686.

Genome annotation databases

EnsembliENST00000295269; ENSP00000295269; ENSG00000180251.
GeneIDi389015.
KEGGihsa:389015.
UCSCiuc002tbz.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL833048 mRNA. Translation: CAH10600.1.
CR627411 mRNA. Translation: CAH10500.1.
AC007278 Genomic DNA. No translation available.
CCDSiCCDS33264.1.
RefSeqiNP_001011552.2. NM_001011552.3.
UniGeneiHs.447686.

3D structure databases

ProteinModelPortaliQ6AI14.
SMRiQ6AI14.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi132934. 2 interactors.
STRINGi9606.ENSP00000295269.

Protein family/group databases

TCDBi2.A.36.1.18. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

iPTMnetiQ6AI14.
PhosphoSitePlusiQ6AI14.

Polymorphism and mutation databases

BioMutaiSLC9A4.
DMDMi296452906.

Proteomic databases

PaxDbiQ6AI14.
PeptideAtlasiQ6AI14.
PRIDEiQ6AI14.

Protocols and materials databases

DNASUi389015.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295269; ENSP00000295269; ENSG00000180251.
GeneIDi389015.
KEGGihsa:389015.
UCSCiuc002tbz.4. human.

Organism-specific databases

CTDi389015.
DisGeNETi389015.
GeneCardsiSLC9A4.
H-InvDBHIX0017462.
HGNCiHGNC:11077. SLC9A4.
HPAiHPA036096.
MIMi600531. gene.
neXtProtiNX_Q6AI14.
OpenTargetsiENSG00000180251.
PharmGKBiPA35933.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
GeneTreeiENSGT00760000119074.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiQ6AI14.
KOiK13961.
OMAiLAFCQIW.
OrthoDBiEOG091G02Q0.
PhylomeDBiQ6AI14.
TreeFamiTF317212.

Enzyme and pathway databases

ReactomeiR-HSA-425986. Sodium/Proton exchangers.

Miscellaneous databases

GenomeRNAii389015.
PROiQ6AI14.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180251.
CleanExiHS_SLC9A4.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001953. Na/H_exchanger_2.
IPR004709. NaH_exchanger.
IPR032103. NHE_CaM-bd.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 1 hit.
PfamiPF00999. Na_H_Exchanger. 1 hit.
PF16644. NEXCaM_BD. 1 hit.
[Graphical view]
PRINTSiPR01084. NAHEXCHNGR.
PR01086. NAHEXCHNGR2.
TIGRFAMsiTIGR00840. b_cpa1. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiSL9A4_HUMAN
AccessioniPrimary (citable) accession number: Q6AI14
Secondary accession number(s): Q69YK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 113 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

The number, localization and denomination of hydrophobic domains in the Na+/H+ exchangers vary among authors.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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.