Sodium/Hydrogen Exchanger 1 (NHE1)

SLC9A1; APNH; Solute Carrier Family 9 Member 1,Sodium/Hydrogen Exchanger; Antiporter,Na+/H+,Amiloride Sensitive; Na(+)/H(+) antiporter, amiloride-sensitive

SPN	S386
HGNC	11071
MGI	102462
PubMed	21592827
RGD	3718
UniProt	P19634
Wiki	SLC9A1

The antiporter is a ubiquitous membrane-bound enzyme involved in volume- and pH-regulation of vertebrate cells. It is inhibited by the non-specific diuretic drug amiloride and activated by a variety of signals including growth factors, mitogens, neurotransmitters, tumor promoters, and others.The gene was first disrupted in mouse fibroblasts. The lost function was then restored by transfection with human genomic DNA. Clones containing these specific human sequences were isolated. One genomic fragment was identified as an exon-coding sequence from the sodium-hydrogen ion antiporter gene by demonstration that it could complement antiporter deficiency in mouse cells; that it recognized an mRNA in cells expressing antiport activity but not in deficient cells; and that it was amplified in variants overexpressing antiport activity.

Reference

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Cell 56:271-280(1989) [PubMed] [Europe PMC] [Abstract]

"Growth factors induce phosphorylation of the Na+/H+ antiporter, glycoprotein of 110 kD."
Science 247:723-726(1990) [PubMed] [Europe PMC] [Abstract]

"Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchanger."
EMBO J. 10:1957-1967(1991) [PubMed] [Europe PMC] [Abstract]

"Cloning and analysis of the human myocardial Na+/H+ exchanger."
Mol. Cell. Biochem. 125:137-143(1993) [PubMed] [Europe PMC] [Abstract]

"Silent polymorphisms within the coding region of human sodium/hydrogen exchanger isoform-1 cDNA in peripheral blood mononuclear cells of leukemia patients: a comparison with healthy controls."
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Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The Na+/H+ exchanger NHE-1 possesses N- and O-linked glycosylation restricted to the first N-terminal extracellular domain."
Biochemistry 33:10463-10469(1994) [PubMed] [Europe PMC] [Abstract]

"Coimmunoprecipitation of a 24-kDa protein with NHE1, the ubiquitous isoform of the Na+/H+ exchanger."
Am. J. Physiol. 270:C1493-C1502(1996) [PubMed] [Europe PMC] [Abstract]

"A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange."
Proc. Natl. Acad. Sci. U.S.A. 93:12631-12636(1996) [PubMed] [Europe PMC] [Abstract]

"Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage."
Am. J. Physiol. 275:C431-C439(1998) [PubMed] [Europe PMC] [Abstract]

"A novel topology model of the human Na(+)/H(+) exchanger isoform 1."
J. Biol. Chem. 275:7942-7949(2000) [PubMed] [Europe PMC] [Abstract]

"Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger type-1."
FEBS Lett. 507:331-335(2001) [PubMed] [Europe PMC] [Abstract]

"Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers."
J. Biol. Chem. 276:17367-17372(2001) [PubMed] [Europe PMC] [Abstract]

"Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger."
J. Biol. Chem. 277:43771-43777(2002) [PubMed] [Europe PMC] [Abstract]

"The Na+/H+ exchanger cytoplasmic tail: structure, function, and interactions with tescalcin."
Biochemistry 42:7448-7456(2003) [PubMed] [Europe PMC] [Abstract]

"Role of calcineurin B homologous protein in pH regulation by the Na+/H+ exchanger 1: tightly bound Ca2+ ions as important structural elements."
Biochemistry 43:3628-3636(2004) [PubMed] [Europe PMC] [Abstract]

"Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1."
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"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]

"Phosphoproteome of resting human platelets."
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"A quantitative atlas of mitotic phosphorylation."
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"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Nuclear accumulation of calcineurin B homologous protein 2 (CHP2) results in enhanced proliferation of tumor cells."
Genes Cells 16:416-426(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger."
J. Biol. Chem. 280:17863-17872(2005) [PubMed] [Europe PMC] [Abstract]

"Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1."
Acta Crystallogr. F 61:956-958(2005) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation."
EMBO J. 25:2315-2325(2006) [PubMed] [Europe PMC] [Abstract]

"Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1."
J. Biol. Chem. 282:2741-2751(2007) [PubMed] [Europe PMC] [Abstract]