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P26434

- SL9A4_RAT

UniProt

P26434 - SL9A4_RAT

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Protein

Sodium/hydrogen exchanger 4

Gene

Slc9a4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein 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.3 Publications

GO - Molecular functioni

  1. sodium:proton antiporter activity Source: InterPro

GO - Biological processi

  1. regulation of pH Source: InterPro
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3721. Slc9a4.

Subcellular locationi

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 717717Sodium/hydrogen exchanger 4PRO_0000052359Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence Analysis
Cross-linki352 – 352Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

May be phosphorylated.

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP26434.
PRIDEiP26434.

Expressioni

Tissue specificityi

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.9 Publications

Gene expression databases

GenevestigatoriP26434.

Interactioni

Subunit structurei

Interacts with CHP1 and CHP2.1 Publication

Protein-protein interaction databases

IntActiP26434. 2 interactions.
STRINGi10116.ENSRNOP00000020716.

Structurei

3D structure databases

ProteinModelPortaliP26434.
SMRiP26434. Positions 124-150, 219-244.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1313CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini29 – 6941CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini91 – 944CytoplasmicSequence Analysis
Topological domaini115 – 12713ExtracellularSequence AnalysisAdd
BLAST
Topological domaini149 – 1546CytoplasmicSequence Analysis
Topological domaini176 – 19116ExtracellularSequence AnalysisAdd
BLAST
Topological domaini217 – 2259CytoplasmicSequence Analysis
Topological domaini248 – 26922ExtracellularSequence AnalysisAdd
BLAST
Topological domaini291 – 30414CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini326 – 35631ExtracellularSequence AnalysisAdd
BLAST
Topological domaini378 – 3847CytoplasmicSequence Analysis
Topological domaini406 – 42015ExtracellularSequence AnalysisAdd
BLAST
Topological domaini442 – 4509ExtracellularSequence Analysis
Topological domaini472 – 717246CytoplasmicSequence AnalysisAdd
BLAST

Intramembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Intramembranei14 – 2815Name=A/M1Sequence AnalysisAdd
BLAST
Intramembranei70 – 9021Name=B/M2Sequence AnalysisAdd
BLAST
Intramembranei421 – 44121Name=LSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei95 – 11420Helical; Name=C/M3Sequence AnalysisAdd
BLAST
Transmembranei128 – 14821Helical; Name=D/M4Sequence AnalysisAdd
BLAST
Transmembranei155 – 17521Helical; Name=E/M5Sequence AnalysisAdd
BLAST
Transmembranei192 – 21625Helical; Name=F/M5ASequence AnalysisAdd
BLAST
Transmembranei226 – 24722Helical; Name=G/M5BSequence AnalysisAdd
BLAST
Transmembranei270 – 29021Helical; Name=H/M6Sequence AnalysisAdd
BLAST
Transmembranei305 – 32521Helical; Name=I/M7Sequence AnalysisAdd
BLAST
Transmembranei357 – 37721Helical; Name=J/M8Sequence AnalysisAdd
BLAST
Transmembranei385 – 40521Helical; Name=K/M9Sequence AnalysisAdd
BLAST
Transmembranei451 – 47121Helical; Name=M/M10Sequence AnalysisAdd
BLAST

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0025.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP26434.
KOiK13961.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

P26434-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGPAMLRAFS SWKWLLLLMV LTCLEASSYV NESSSPTGQQ TPDARFAASS
60 70 80 90 100
SDPDERISVF ELDYDYVQIP YEVTLWILLA SLAKIGFHLY HRLPHLMPES
110 120 130 140 150
CLLIIVGALV GSIIFGTHHK SPPVMDSSIY FLYLLPPIVL ESGYFMPTRP
160 170 180 190 200
FFENIGSILW WAGLGALINA FGIGLSLYFI CQIKAFGLGD INLLQNLLFG
210 220 230 240 250
SLISAVDPVA VLAVFEEARV NEQLYMMIFG EALLNDGISV VLYNILIAFT
260 270 280 290 300
KMHKFEDIEA VDILAGCARF VIVGCGGVFF GIIFGFISAF ITRFTQNISA
310 320 330 340 350
IEPLIVFMFS YLSYLAAETL YLSGILAITA CAVTMKKYVE ENVSQTSYTT
360 370 380 390 400
IKYFMKMLSS VSETLIFIFM GVSTVGKNHE WNWAFVCFTL AFCQIWRAIS
410 420 430 440 450
VFTLFYVSNQ FRTFPFSIKD QLIIFYSGVR GAGSFSLAFL LPLTLFPRKK
460 470 480 490 500
LFVTATLVVT YFTVFFQGIT IGPLVRYLDV RKTNKKESIN EELHIRLMDH
510 520 530 540 550
LKAGIEDVCG QWSHYQVRDK FKKFDHRYLR KILIRRNQPK SSIVSLYKKL
560 570 580 590 600
EMKQAIEMAE TGLLSSVASP TPYQSERIQG IKRLSPEDVE SMRDILTRNM
610 620 630 640 650
YQVRQRTLSY NKYNLKPQTS EKQAKEILIR RQNTLRESLR KGQSLPWVKP
660 670 680 690 700
AGTKNFRYLS FPYSNPQPAR RGARAAESTG NPCCWLLHFL LCRAMVEKIW
710
GPGGQETQPR LLCRNLN
Length:717
Mass (Da):81,522
Last modified:August 1, 1992 - v1
Checksum:i4EFBBEC7D7782753
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M85301 mRNA. Translation: AAA41703.1.
PIRiC40204.
RefSeqiNP_775121.1. NM_173098.1.
UniGeneiRn.9707.

Genome annotation databases

GeneIDi24785.
KEGGirno:24785.
UCSCiRGD:3721. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M85301 mRNA. Translation: AAA41703.1 .
PIRi C40204.
RefSeqi NP_775121.1. NM_173098.1.
UniGenei Rn.9707.

3D structure databases

ProteinModelPortali P26434.
SMRi P26434. Positions 124-150, 219-244.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P26434. 2 interactions.
STRINGi 10116.ENSRNOP00000020716.

Proteomic databases

PaxDbi P26434.
PRIDEi P26434.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 24785.
KEGGi rno:24785.
UCSCi RGD:3721. rat.

Organism-specific databases

CTDi 389015.
RGDi 3721. Slc9a4.

Phylogenomic databases

eggNOGi COG0025.
HOGENOMi HOG000247044.
HOVERGENi HBG052615.
InParanoidi P26434.
KOi K13961.

Miscellaneous databases

NextBioi 604404.
PROi P26434.

Gene expression databases

Genevestigatori P26434.

Family and domain databases

InterProi IPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001953. Na/H_exchanger_2.
IPR004709. NaH_exchanger.
[Graphical view ]
PANTHERi PTHR10110. PTHR10110. 1 hit.
Pfami PF00999. Na_H_Exchanger. 1 hit.
[Graphical view ]
PRINTSi PR01084. NAHEXCHNGR.
PR01086. NAHEXCHNGR2.
TIGRFAMsi TIGR00840. b_cpa1. 1 hit.
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiSL9A4_RAT
AccessioniPrimary (citable) accession number: P26434
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: October 29, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3