NHX1 bifunctional K:H/Na:H antiporter NHX1 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: NHX1
Official Full Name: bifunctional K:H/Na:H antiporter NHX1
Primary source: SGD:S000002864
Locus tag: YDR456W
See related: AllianceGenome:SGD:S000002864; FungiDB:YDR456W; VEuPathDB:YDR456W
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: NHA2; VPL27; VPS44
Summary: Enables potassium:proton antiporter activity and sodium:proton antiporter activity. Involved in monoatomic cation transmembrane transport; multivesicular body-lysosome fusion; and vacuolar acidification. Located in early endosome; late endosome; and trans-Golgi network. Is active in fungal-type vacuole membrane. Human ortholog(s) of this gene implicated in Christianson syndrome; X-linked intellectual developmental disorder 108; and autistic disorder. Orthologous to several human genes including SLC9A9 (solute carrier family 9 member A9). [provided by Alliance of Genome Resources, Apr 2025]
Orthologs: all
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Genomic context

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See NHX1 in Genome Data Viewer

Location:: chromosome: IV

Exon count:: 1

Sequence:: Chromosome: IV; NC_001136.10 (1367485..1369386)

Chromosome IV - NC_001136.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001136.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Data suggest that Nhx1p plays an important role in regulation of the luminal pH of various intracellular organelles, and that this regulation is critical for the protein recycling pathway as well as the endocytic pathway.
Title: Localization and functional requirement of yeast Na+/H+ exchanger, Nhx1p, in the endocytic and protein recycling pathway.
Nhx1 is not required for cargo sorting or multivesicular body formation and shows synthetic phenotypes with select endosomal sorting complex required for transport mutants
Title: Endosomal Na+ (K+)/H+ exchanger Nhx1/Vps44 functions independently and downstream of multivesicular body formation.
Nhx1p contributes to MVB formation by the recruitment of Vps27p to the endosomal membrane, possibly through Nhx1p antiporter activity.
Title: The endosomal Na(+)/H(+) exchanger contributes to multivesicular body formation by regulating the recruitment of ESCRT-0 Vps27p to the endosomal membrane.
The authors conclude that Arl1p, Kha1p and Nhx1p collaborate in survival strategies at nonoptimal pH, temperatures and cation concentrations, but work independent of each other.
Title: Genetic interactions among the Arl1 GTPase and intracellular Na(+) /H(+) antiporters in pH homeostasis and cation detoxification.
Gene knockout of NHX1 increases sensitivity to hygromycin and acidic pH in yeast cells.
Title: Saccharomyces cerevisiae glucose signalling regulator Mth1p regulates the organellar Na+/H+ exchanger Nhx1p.
analysis of the relative importance of Nhx1p, Vnx1p, and Vcx1p in the vacuolar accumulation of monovalent cations
Title: Vacuolar cation/H+ antiporters of Saccharomyces cerevisiae.
The trafficking phenotypes of all Nhx1 mutants, including hygromycin-sensitivity and missorting of carboxypeptidase Y, were found to directly correlate with pH homoeostasis defects and could be proportionately corrected by titration with weak base.
Title: Mutational analysis of the intramembranous H10 loop of yeast Nhx1 reveals a critical role in ion homoeostasis and vesicle trafficking.
the Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking
Title: The yeast endosomal Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking.
The high sequence conservation within this subfamily of yeast antiporters suggests that Nhx1p is of great importance in cell physiology
Title: Exploration of yeast alkali metal cation/H+ antiporters: sequence and structure comparison.

Submit: New GeneRIF Correction

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables antiporter activity	IEA Inferred from Electronic Annotation more info
enables potassium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables potassium:proton antiporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables sodium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium:proton antiporter activity	IEA Inferred from Electronic Annotation more info
enables sodium:proton antiporter activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in intracellular monoatomic cation homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic cation transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proton transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of pH	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion transport	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in vacuolar acidification	IBA Inferred from Biological aspect of Ancestor more info
involved_in vacuolar acidification	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in early endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	HDA more info	PubMed
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
is_active_in fungal-type vacuole membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in fungal-type vacuole membrane	IDA Inferred from Direct Assay more info	PubMed
located_in fungal-type vacuole membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in late endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: bifunctional K:H/Na:H antiporter NHX1

NP_010744.3

Na+/H+ and K+/H+ exchanger; required for intracellular sequestration of Na+ and K+; located in the vacuole and late endosome compartments; required for osmotolerance to acute hypertonic shock and for vacuolar fusion; ortholog of human NHE9, which is linked to autism