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P26434 (SL9A4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/hydrogen exchanger 4
Alternative name(s):
Na(+)/H(+) exchanger 4
Short name=NHE-4
Solute carrier family 9 member 4
Gene names
Name:Slc9a4
Synonyms:Nhe4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length717 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.3 Ref.4

Subunit structure

Interacts with CHP1 and CHP2. Ref.10

Subcellular location

Apical cell membrane; Multi-pass membrane protein. Basolateral cell membrane; Multi-pass membrane protein. Cytoplasmic granule membrane; Multi-pass membrane protein. Note: Found in zymogen granule membranes. Ref.6 Ref.7 Ref.9

Tissue specificity

Most abundant in stomach, followed by colon. Lesser amounts were found in kidney, liver, brain, uterus and skeletal muscle. Predominantly expressed in the inner segments of inner medullary collecting ducts (IMCD) in kidney. Highly expressed in the cavi amnoni fields of hippocampus. Expressed in pancreas. Expressed in multiple nephron segments including proximla tubules, medullar thick ascending limbs (MTAL), cortical thick ascending limbs (CTAL), distal covoluted tubules and cortical and medullary collecting ducts. Expressed in submandibular gland. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11

Post-translational modification

May be phosphorylated.

Sequence similarities

Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]

Caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 717717Sodium/hydrogen exchanger 4
PRO_0000052359

Regions

Topological domain1 – 1313Cytoplasmic Potential
Intramembrane14 – 2815Name=A/M1; Potential
Topological domain29 – 6941Cytoplasmic Potential
Intramembrane70 – 9021Name=B/M2; Potential
Topological domain91 – 944Cytoplasmic Potential
Transmembrane95 – 11420Helical; Name=C/M3; Potential
Topological domain115 – 12713Extracellular Potential
Transmembrane128 – 14821Helical; Name=D/M4; Potential
Topological domain149 – 1546Cytoplasmic Potential
Transmembrane155 – 17521Helical; Name=E/M5; Potential
Topological domain176 – 19116Extracellular Potential
Transmembrane192 – 21625Helical; Name=F/M5A; Potential
Topological domain217 – 2259Cytoplasmic Potential
Transmembrane226 – 24722Helical; Name=G/M5B; Potential
Topological domain248 – 26922Extracellular Potential
Transmembrane270 – 29021Helical; Name=H/M6; Potential
Topological domain291 – 30414Cytoplasmic Potential
Transmembrane305 – 32521Helical; Name=I/M7; Potential
Topological domain326 – 35631Extracellular Potential
Transmembrane357 – 37721Helical; Name=J/M8; Potential
Topological domain378 – 3847Cytoplasmic Potential
Transmembrane385 – 40521Helical; Name=K/M9; Potential
Topological domain406 – 42015Extracellular Potential
Intramembrane421 – 44121Name=L; Potential
Topological domain442 – 4509Extracellular Potential
Transmembrane451 – 47121Helical; Name=M/M10; Potential
Topological domain472 – 717246Cytoplasmic Potential

Amino acid modifications

Glycosylation3421N-linked (GlcNAc...) Potential
Cross-link352Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
P26434 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 4EFBBEC7D7782753

FASTA71781,522
        10         20         30         40         50         60 
MGPAMLRAFS SWKWLLLLMV LTCLEASSYV NESSSPTGQQ TPDARFAASS SDPDERISVF 

        70         80         90        100        110        120 
ELDYDYVQIP YEVTLWILLA SLAKIGFHLY HRLPHLMPES CLLIIVGALV GSIIFGTHHK 

       130        140        150        160        170        180 
SPPVMDSSIY FLYLLPPIVL ESGYFMPTRP FFENIGSILW WAGLGALINA FGIGLSLYFI 

       190        200        210        220        230        240 
CQIKAFGLGD INLLQNLLFG SLISAVDPVA VLAVFEEARV NEQLYMMIFG EALLNDGISV 

       250        260        270        280        290        300 
VLYNILIAFT KMHKFEDIEA VDILAGCARF VIVGCGGVFF GIIFGFISAF ITRFTQNISA 

       310        320        330        340        350        360 
IEPLIVFMFS YLSYLAAETL YLSGILAITA CAVTMKKYVE ENVSQTSYTT IKYFMKMLSS 

       370        380        390        400        410        420 
VSETLIFIFM GVSTVGKNHE WNWAFVCFTL AFCQIWRAIS VFTLFYVSNQ FRTFPFSIKD 

       430        440        450        460        470        480 
QLIIFYSGVR GAGSFSLAFL LPLTLFPRKK LFVTATLVVT YFTVFFQGIT IGPLVRYLDV 

       490        500        510        520        530        540 
RKTNKKESIN EELHIRLMDH LKAGIEDVCG QWSHYQVRDK FKKFDHRYLR KILIRRNQPK 

       550        560        570        580        590        600 
SSIVSLYKKL EMKQAIEMAE TGLLSSVASP TPYQSERIQG IKRLSPEDVE SMRDILTRNM 

       610        620        630        640        650        660 
YQVRQRTLSY NKYNLKPQTS EKQAKEILIR RQNTLRESLR KGQSLPWVKP AGTKNFRYLS 

       670        680        690        700        710 
FPYSNPQPAR RGARAAESTG NPCCWLLHFL LCRAMVEKIW GPGGQETQPR LLCRNLN 

« Hide

References

[1]"Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE-1 and two structurally related proteins."
Orlowski J., Kandasamy R.A., Shull G.E.
J. Biol. Chem. 267:9331-9339(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Stomach.
[2]"A unique sodium-hydrogen exchange isoform (NHE-4) of the inner medulla of the rat kidney is induced by hyperosmolarity."
Bookstein C., Musch M.W., DePaoli A., Xie Y., Villereal M., Rao M.C., Chang E.B.
J. Biol. Chem. 269:29704-29709(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[3]"Characterization of the rat Na+/H+ exchanger isoform NHE4 and localization in rat hippocampus."
Bookstein C., Musch M.W., DePaoli A., Xie Y., Rabenau K., Villereal M., Rao M.C., Chang E.B.
Am. J. Physiol. 271:C1629-C1638(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[4]"Heterologous expression of rat NHE4: a highly amiloride-resistant Na+/H+ exchanger isoform."
Chambrey R., Achard J.-M., Warnock D.G.
Am. J. Physiol. 272:C90-C98(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Tissue distribution of Na+/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney."
Bookstein C., Xie Y., Rabenau K., Musch M.W., McSwine R.L., Rao M.C., Chang E.B.
Am. J. Physiol. 273:C1496-C1505(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Immunochemical characterization of Na+/H+ exchanger isoform NHE4."
Pizzonia J.H., Biemesderfer D., Abu-Alfa A.K., Wu M.-S., Exner M., Isenring P., Igarashi P., Aronson P.S.
Am. J. Physiol. 275:F510-F517(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"Expression of NHE1 and NHE4 in rat pancreatic zymogen granule membranes."
Anderie I., Blum R., Haase W., Grinstein S., Thevenod F.
Biochem. Biophys. Res. Commun. 246:330-336(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]"Expression of Na+/H+ exchanger isoforms in inner segment of inner medullary collecting duct."
Sun A.M., Liu Y., Centracchio J., Dworkin L.D.
J. Membr. Biol. 164:293-300(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Localization and functional characterization of Na+/H+ exchanger isoform NHE4 in rat thick ascending limbs."
Chambrey R., St John P.L., Eladari D., Quentin F., Warnock D.G., Abrahamson D.R., Podevin R.-A., Paillard M.
Am. J. Physiol. 281:F707-F717(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]"Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium."
Inoue H., Nakamura Y., Nagita M., Takai T., Masuda M., Nakamura N., Kanazawa H.
Biol. Pharm. Bull. 26:148-155(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CHP1 AND CHP2.
[11]"Na(+)/H(+) exchanger isoforms are differentially regulated in rat submandibular gland during acid/base disturbances in vivo."
Oehlke O., Sprysch P., Rickmann M., Roussa E.
Cell Tissue Res. 323:253-262(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M85301 mRNA. Translation: AAA41703.1.
PIRC40204.
RefSeqNP_775121.1. NM_173098.1.
UniGeneRn.9707.

3D structure databases

ProteinModelPortalP26434.
SMRP26434. Positions 124-150, 219-244.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP26434. 2 interactions.
STRING10116.ENSRNOP00000020716.

Proteomic databases

PaxDbP26434.
PRIDEP26434.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24785.
KEGGrno:24785.
UCSCRGD:3721. rat.

Organism-specific databases

CTD389015.
RGD3721. Slc9a4.

Phylogenomic databases

eggNOGCOG0025.
HOGENOMHOG000247044.
HOVERGENHBG052615.
InParanoidP26434.
KOK13961.

Gene expression databases

GenevestigatorP26434.

Family and domain databases

InterProIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001953. Na/H_exchanger_2.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERPTHR10110. PTHR10110. 1 hit.
PfamPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
PRINTSPR01084. NAHEXCHNGR.
PR01086. NAHEXCHNGR2.
TIGRFAMsTIGR00840. b_cpa1. 1 hit.
ProtoNetSearch...

Other

NextBio604404.
PROP26434.

Entry information

Entry nameSL9A4_RAT
AccessionPrimary (citable) accession number: P26434
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: April 16, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families