UniProtKB - Q6AI14 (SL9A4_HUMAN)
Protein
Sodium/hydrogen exchanger 4
Gene
SLC9A4
Organism
Homo sapiens (Human)
Status
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
Caution
The number, localization and denomination of hydrophobic domains in the Na+/H+ exchangers vary among authors.Curated
GO - Molecular functioni
- potassium:proton antiporter activity Source: GO_Central
- sodium:proton antiporter activity Source: GO_Central
GO - Biological processi
- epithelial cell development Source: Ensembl
- gastric acid secretion Source: Ensembl
- ion transport Source: Reactome
- potassium ion homeostasis Source: InterPro
- potassium ion transmembrane transport Source: GO_Central
- regulation of intracellular pH Source: GO_Central
- response to salt stress Source: InterPro
- sodium ion import across plasma membrane Source: GO_Central
Keywordsi
Biological process | Antiport, Ion transport, Sodium transport, Transport |
Ligand | Sodium |
Enzyme and pathway databases
PathwayCommonsi | Q6AI14 |
Reactomei | R-HSA-425986, Sodium/Proton exchangers |
Protein family/group databases
TCDBi | 2.A.36.1.18, the monovalent cation:proton antiporter-1 (cpa1) family |
Names & Taxonomyi
Protein namesi | Recommended name: Sodium/hydrogen exchanger 4Alternative name(s): Na(+)/H(+) exchanger 4 Short name: NHE-4 Solute carrier family 9 member 4 |
Gene namesi | Name:SLC9A4 Synonyms:NHE4 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11077, SLC9A4 |
MIMi | 600531, gene |
neXtProti | NX_Q6AI14 |
VEuPathDBi | HostDB:ENSG00000180251.4 |
Subcellular locationi
Plasma membrane
- Apical cell membrane By similarity; Multi-pass membrane protein By similarity
- Basolateral cell membrane By similarity; Multi-pass membrane protein By similarity
Other locations
- Cytoplasmic granule membrane By similarity; Multi-pass membrane protein By similarity
Note: Found in zymogen granule membranes.By similarity
Plasma Membrane
- apical plasma membrane Source: UniProtKB-SubCell
- basolateral plasma membrane Source: UniProtKB-SubCell
- plasma membrane Source: GO_Central
Other locations
- integral component of membrane Source: UniProtKB-KW
- vacuolar membrane Source: InterPro
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 13 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Intramembranei | 14 – 28 | Name=A/M1Sequence analysisAdd BLAST | 15 | |
Topological domaini | 29 – 69 | CytoplasmicSequence analysisAdd BLAST | 41 | |
Intramembranei | 70 – 90 | Name=B/M2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 91 – 94 | CytoplasmicSequence analysis | 4 | |
Transmembranei | 95 – 115 | Helical; Name=C/M3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 116 – 127 | ExtracellularSequence analysisAdd BLAST | 12 | |
Transmembranei | 128 – 148 | Helical; Name=D/M4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 149 – 154 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 155 – 175 | Helical; Name=E/M5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 176 – 196 | ExtracellularSequence analysisAdd BLAST | 21 | |
Transmembranei | 197 – 217 | Helical; Name=F/M5ASequence analysisAdd BLAST | 21 | |
Topological domaini | 218 – 226 | CytoplasmicSequence analysis | 9 | |
Transmembranei | 227 – 247 | Helical; Name=G/M5BSequence analysisAdd BLAST | 21 | |
Topological domaini | 248 – 270 | ExtracellularSequence analysisAdd BLAST | 23 | |
Transmembranei | 271 – 291 | Helical; Name=H/M6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 292 – 304 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Transmembranei | 305 – 325 | Helical; Name=I/M7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 326 – 356 | ExtracellularSequence analysisAdd BLAST | 31 | |
Transmembranei | 357 – 373 | Helical; Name=J/M8Sequence analysisAdd BLAST | 17 | |
Topological domaini | 374 – 384 | CytoplasmicSequence analysisAdd BLAST | 11 | |
Transmembranei | 385 – 405 | Helical; Name=K/M9Sequence analysisAdd BLAST | 21 | |
Topological domaini | 406 – 420 | ExtracellularSequence analysisAdd BLAST | 15 | |
Intramembranei | 421 – 441 | Name=LSequence analysisAdd BLAST | 21 | |
Topological domaini | 442 – 450 | ExtracellularSequence analysis | 9 | |
Transmembranei | 451 – 471 | Helical; Name=M/M10Sequence analysisAdd BLAST | 21 | |
Topological domaini | 472 – 798 | CytoplasmicSequence analysisAdd BLAST | 327 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 389015 |
OpenTargetsi | ENSG00000180251 |
PharmGKBi | PA35933 |
Miscellaneous databases
Pharosi | Q6AI14, Tdark |
Genetic variation databases
BioMutai | SLC9A4 |
DMDMi | 296452906 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000314665 | 1 – 798 | Sodium/hydrogen exchanger 4Add BLAST | 798 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 342 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
May be phosphorylated.By similarity
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
MassIVEi | Q6AI14 |
PaxDbi | Q6AI14 |
PeptideAtlasi | Q6AI14 |
PRIDEi | Q6AI14 |
ProteomicsDBi | 66186 |
PTM databases
GlyGeni | Q6AI14, 1 site |
iPTMneti | Q6AI14 |
PhosphoSitePlusi | Q6AI14 |
Expressioni
Gene expression databases
Bgeei | ENSG00000180251, Expressed in stomach and 55 other tissues |
Organism-specific databases
HPAi | ENSG00000180251, Group enriched (gallbladder, kidney, stomach) |
Interactioni
Subunit structurei
Interacts with CHP1 and CHP2.
By similarityProtein-protein interaction databases
BioGRIDi | 132934, 2 interactors |
STRINGi | 9606.ENSP00000295269 |
Miscellaneous databases
RNActi | Q6AI14, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1966, Eukaryota |
GeneTreei | ENSGT00940000160774 |
HOGENOMi | CLU_005912_4_3_1 |
InParanoidi | Q6AI14 |
OMAi | REHHKSH |
OrthoDBi | 316731at2759 |
PhylomeDBi | Q6AI14 |
TreeFami | TF317212 |
Family and domain databases
InterProi | View protein in InterPro IPR006153, Cation/H_exchanger IPR018422, Cation/H_exchanger_CPA1 IPR001953, Na/H_exchanger_2 IPR004709, NaH_exchanger IPR032103, NHE_CaM-bd IPR036958, NHX4 |
PANTHERi | PTHR10110, PTHR10110, 1 hit PTHR10110:SF103, PTHR10110:SF103, 1 hit |
Pfami | View protein in Pfam PF00999, Na_H_Exchanger, 1 hit PF16644, NEXCaM_BD, 1 hit |
PRINTSi | PR01084, NAHEXCHNGR PR01086, NAHEXCHNGR2 |
TIGRFAMsi | TIGR00840, b_cpa1, 1 hit |
i Sequence
Sequence statusi: Complete.
Q6AI14-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 429 | V → A in CAH10500 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 784 | G → S in CAH10500 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 784 | G → S in CAH10600 (PubMed:17974005).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_056209 | 116 | G → S. Corresponds to variant dbSNP:rs17027275Ensembl. | 1 | |
Natural variantiVAR_056210 | 581 | I → V. Corresponds to variant dbSNP:rs6742280Ensembl. | 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. |
CCDSi | CCDS33264.1 |
RefSeqi | NP_001011552.2, NM_001011552.3 |
Genome annotation databases
Ensembli | ENST00000295269; ENSP00000295269; ENSG00000180251 |
GeneIDi | 389015 |
KEGGi | hsa:389015 |
UCSCi | uc002tbz.4, human |
Similar proteinsi
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. |
CCDSi | CCDS33264.1 |
RefSeqi | NP_001011552.2, NM_001011552.3 |
3D structure databases
SMRi | Q6AI14 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 132934, 2 interactors |
STRINGi | 9606.ENSP00000295269 |
Protein family/group databases
TCDBi | 2.A.36.1.18, the monovalent cation:proton antiporter-1 (cpa1) family |
PTM databases
GlyGeni | Q6AI14, 1 site |
iPTMneti | Q6AI14 |
PhosphoSitePlusi | Q6AI14 |
Genetic variation databases
BioMutai | SLC9A4 |
DMDMi | 296452906 |
Proteomic databases
MassIVEi | Q6AI14 |
PaxDbi | Q6AI14 |
PeptideAtlasi | Q6AI14 |
PRIDEi | Q6AI14 |
ProteomicsDBi | 66186 |
Protocols and materials databases
Antibodypediai | 49172, 10 antibodies |
DNASUi | 389015 |
Genome annotation databases
Ensembli | ENST00000295269; ENSP00000295269; ENSG00000180251 |
GeneIDi | 389015 |
KEGGi | hsa:389015 |
UCSCi | uc002tbz.4, human |
Organism-specific databases
CTDi | 389015 |
DisGeNETi | 389015 |
GeneCardsi | SLC9A4 |
HGNCi | HGNC:11077, SLC9A4 |
HPAi | ENSG00000180251, Group enriched (gallbladder, kidney, stomach) |
MIMi | 600531, gene |
neXtProti | NX_Q6AI14 |
OpenTargetsi | ENSG00000180251 |
PharmGKBi | PA35933 |
VEuPathDBi | HostDB:ENSG00000180251.4 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1966, Eukaryota |
GeneTreei | ENSGT00940000160774 |
HOGENOMi | CLU_005912_4_3_1 |
InParanoidi | Q6AI14 |
OMAi | REHHKSH |
OrthoDBi | 316731at2759 |
PhylomeDBi | Q6AI14 |
TreeFami | TF317212 |
Enzyme and pathway databases
PathwayCommonsi | Q6AI14 |
Reactomei | R-HSA-425986, Sodium/Proton exchangers |
Miscellaneous databases
BioGRID-ORCSi | 389015, 4 hits in 865 CRISPR screens |
GenomeRNAii | 389015 |
Pharosi | Q6AI14, Tdark |
PROi | PR:Q6AI14 |
RNActi | Q6AI14, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000180251, Expressed in stomach and 55 other tissues |
Family and domain databases
InterProi | View protein in InterPro IPR006153, Cation/H_exchanger IPR018422, Cation/H_exchanger_CPA1 IPR001953, Na/H_exchanger_2 IPR004709, NaH_exchanger IPR032103, NHE_CaM-bd IPR036958, NHX4 |
PANTHERi | PTHR10110, PTHR10110, 1 hit PTHR10110:SF103, PTHR10110:SF103, 1 hit |
Pfami | View protein in Pfam PF00999, Na_H_Exchanger, 1 hit PF16644, NEXCaM_BD, 1 hit |
PRINTSi | PR01084, NAHEXCHNGR PR01086, NAHEXCHNGR2 |
TIGRFAMsi | TIGR00840, b_cpa1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SL9A4_HUMAN | |
Accessioni | Q6AI14Primary (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: | February 10, 2021 | |
This is version 135 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants