Sodium/hydrogen exchanger 4 - Rattus norvegicus (Rat)

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P26434 (SL9A4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 100. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	717 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Antiport Ion transport Sodium transport Transport
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of pH Inferred from electronic annotation. Source: InterPro
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	sodium:hydrogen antiporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 717

717

Sodium/hydrogen exchanger 4

PRO_0000052359

Regions

Topological domain

1 – 13

Cytoplasmic Potential

Intramembrane

14 – 28

Name=A/M1; Potential

Topological domain

29 – 69

Cytoplasmic Potential

Intramembrane

70 – 90

Name=B/M2; Potential

Topological domain

91 – 94

Cytoplasmic Potential

Transmembrane

95 – 114

Helical; Name=C/M3; Potential

Topological domain

115 – 127

Extracellular Potential

Transmembrane

128 – 148

Helical; Name=D/M4; Potential

Topological domain

149 – 154

Cytoplasmic Potential

Transmembrane

155 – 175

Helical; Name=E/M5; Potential

Topological domain

176 – 191

Extracellular Potential

Transmembrane

192 – 216

Helical; Name=F/M5A; Potential

Topological domain

217 – 225

Cytoplasmic Potential

Transmembrane

226 – 247

Helical; Name=G/M5B; Potential

Topological domain

248 – 269

Extracellular Potential

Transmembrane

270 – 290

Helical; Name=H/M6; Potential

Topological domain

291 – 304

Cytoplasmic Potential

Transmembrane

305 – 325

Helical; Name=I/M7; Potential

Topological domain

326 – 356

Extracellular Potential

Transmembrane

357 – 377

Helical; Name=J/M8; Potential

Topological domain

378 – 384

Cytoplasmic Potential

Transmembrane

385 – 405

Helical; Name=K/M9; Potential

Topological domain

406 – 420

Extracellular Potential

Intramembrane

421 – 441

Name=L; Potential

Topological domain

442 – 450

Extracellular Potential

Transmembrane

451 – 471

Helical; Name=M/M10; Potential

Topological domain

472 – 717

246

Cytoplasmic Potential

Amino acid modifications

Glycosylation

342

N-linked (GlcNAc...) Potential

Cross-link

352

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

P26434 [UniParc].

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

FASTA

717

81,522

        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

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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.
IPI	IPI00193372.
PIR	C40204.
RefSeq	NP_775121.1. NM_173098.1.
UniGene	Rn.9707.
3D structure databases
ProteinModelPortal	P26434.
SMR	P26434. Positions 124-150, 219-244.
ModBase	Search...
Protein-protein interaction databases
IntAct	P26434. 2 interactions.
STRING	10116.ENSRNOP00000020716.
Proteomic databases
PaxDb	P26434.
PRIDE	P26434.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24785.
KEGG	rno:24785.
UCSC	RGD:3721. rat.
Organism-specific databases
CTD	389015.
RGD	3721. Slc9a4.
Phylogenomic databases
eggNOG	COG0025.
HOGENOM	HOG000247044.
HOVERGEN	HBG052615.
InParanoid	P26434.
KO	K13961.
Gene expression databases
ArrayExpress	P26434.
Genevestigator	P26434.
Family and domain databases
InterPro	IPR006153. Cation/H_exchanger. IPR018422. Cation/H_exchanger_CPA1. IPR001953. Na/H_exchanger_2. IPR004709. NaH_exchanger. [Graphical view]
PANTHER	PTHR10110. PTHR10110. 1 hit.
Pfam	PF00999. Na_H_Exchanger. 1 hit. [Graphical view]
PRINTS	PR01084. NAHEXCHNGR. PR01086. NAHEXCHNGR2.
TIGRFAMs	TIGR00840. b_cpa1. 1 hit.
ProtoNet	Search...
Other
NextBio	604404.

Entry information

Entry name

SL9A4_RAT

Accession

Primary (citable) accession number: P26434

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	April 3, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents