Sodium/hydrogen exchanger 3

UniProt P48764 Organism Homo sapiens Gene NHE3, SLC9A3

Also known as: NHE3, SLC9A3

Function

Plasma membrane Na(+)/H(+) antiporter. Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry, playing a key role in salt and fluid absorption and pH homeostasis (By similarity). Major apical Na(+)/H(+) exchanger in kidney and intestine playing an important role in renal and intestine Na(+) absorption and blood pressure regulation.

Classification

Family (Pfam): PF00999 Na_H_Exchanger
InterPro: Cation/H_exchanger_CPA1, Cation/H_exchanger_TM, Na/H_exchanger_3/5, NaH_exchanger
Functional cluster: Membrane Transporters & GPCRs

Experimental structures · PDB · 1

7X2U EM 3.20A

A predicted model is available from AlphaFold.

Gene Ontology · 20

Disease associations

congenital secretory sodium diarrhea 8 MONDO:0014808

Drugs targeting this protein · 2

TENAPANOR HYDROCHLORIDE inhibitor
SQUALAMINE LACTATE inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Calcineurin B homologous protein 1 1 shared papers
Sorting nexin-27 1 shared papers
Sodium/hydrogen exchanger 3 2 shared papers
S-adenosylhomocysteine hydrolase-like protein 1 1 shared papers
Sodium/hydrogen exchanger 3 1 shared papers
S-adenosylhomocysteine hydrolase-like protein 1 2 shared papers
Na(+)/H(+) exchange regulatory cofactor NHE-RF4 1 shared papers
Na(+)/H(+) exchange regulatory cofactor NHE-RF4 1 shared papers
Sodium/hydrogen exchanger 3 1 shared papers
Na(+)/H(+) exchange regulatory cofactor NHE-RF2 1 shared papers

Literature · 11 cited papers

Structural basis of autoinhibition of the human NHE3-CHP1 complex. Sci. Adv. · 2022
Congenital sodium diarrhea by mutation of the SLC9A3 gene. Eur. J. Med. Genet. · 2019
Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea. Hum. Mol. Genet. · 2015
Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3. Mol. Biol. Cell · 2015
Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans. Sci. Transl. Med. · 2014
Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II. J. Biol. Chem. · 2010
Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism. Cell. Physiol. Biochem. · 2008
IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in response to calcium. J. Biol. Chem. · 2008
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
The DNA sequence and comparative analysis of human chromosome 5. Nature · 2004
Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3. Am. J. Physiol. · 1995

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