Epithelial sodium channel subunit alpha
Also known as: SCNN1, SCNN1A
Function
This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis. ENaC operates in epithelial tissues, where it mediates the electrodiffusion of sodium ions from extracellular fluid through the apical membrane of cells, with water following osmotically. It plays a key role in maintaining sodium homeostasis through electrogenic sodium reabsorption in the kidneys. Additionally, ENaC is essential for airway surface liquid homeostasis, which is crucial for proper mucus clearance.
Classification
- Family (Pfam)
- PF00858 ASC
- InterPro
- ENaC, ENaC_chordates, ENaC_CS
- Functional cluster
- Radical SAM Enzymes
Experimental structures · PDB · 3
A predicted model is available from AlphaFold.
Gene Ontology · 24
- GO:0001669 acrosomal vesicle
- GO:0016324 apical plasma membrane
- GO:0060170 ciliary membrane
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0009897 external side of plasma membrane
- GO:0070062 extracellular exosome
- GO:0031514 motile cilium
- GO:0005886 plasma membrane
- GO:0034706 sodium channel complex
- GO:0097228 sperm principal piece
- GO:0015280 ligand-gated sodium channel activity
- GO:0050699 WW domain binding
- GO:0071468 cellular response to acidic pH
- GO:1904045 cellular response to aldosterone
- GO:1904117 cellular response to vasopressin
- GO:0006883 intracellular sodium ion homeostasis
- GO:0050891 multicellular organismal-level water homeostasis
- GO:0008217 regulation of blood pressure
- GO:0050914 sensory perception of salty taste
- GO:0050915 sensory perception of sour taste
- GO:0055078 sodium ion homeostasis
- GO:0098719 sodium ion import across plasma membrane
- GO:0035725 sodium ion transmembrane transport
Disease associations
- pseudohypoaldosteronism, type IB1, autosomal recessive MONDO:0009917
- bronchiectasis with or without elevated sweat chloride 2 MONDO:0013087
- Liddle syndrome 3 MONDO:0029132
Drugs targeting this protein · 3
- AMILORIDE HYDROCHLORIDE blocker
- IDREVLORIDE blocker
- TRIAMTERENE blocker
Related proteins · sequence + function similarity
- Epithelial sodium channel subunit alpha 0.99
- Epithelial sodium channel subunit alpha 0.98
- Epithelial sodium channel subunit alpha 0.98
- Epithelial sodium channel subunit alpha 0.98
- Epithelial sodium channel subunit alpha 0.97
- Epithelial sodium channel subunit alpha 0.97
- Epithelial sodium channel subunit alpha 0.85
- Epithelial sodium channel subunit alpha 0.83
- Epithelial sodium channel subunit beta 0.79
- Acid-sensing ion channel 4 0.79
- Acid-sensing ion channel 4 0.79
- Acid-sensing ion channel 4 0.78
Co-cited proteins · studied together in the literature
- Epithelial sodium channel subunit beta 18 shared papers
- Epithelial sodium channel subunit gamma 13 shared papers
- Cystic fibrosis transmembrane conductance regulator 2 shared papers
- E3 ubiquitin-protein ligase NEDD4 1 shared papers
- Epithelial sodium channel subunit alpha 1 shared papers
- BPI fold-containing family A member 1 1 shared papers
- Epithelial sodium channel subunit delta 1 shared papers
- Mineralocorticoid receptor 1 shared papers
- NEDD4-like E3 ubiquitin-protein ligase WWP2 2 shared papers
- Epithelial sodium channel subunit alpha 2 shared papers
- E3 ubiquitin-protein ligase NEDD4-like 2 shared papers
- Proprotein convertase subtilisin/kexin type 9 1 shared papers
Literature · 37 cited papers
- Molecular principles of assembly, activation, and inhibition in epithelial sodium channel. Elife · 2020
- Structure of the human epithelial sodium channel by cryo-electron microscopy. Elife · 2018
- A Missense Mutation in the Extracellular Domain of alphaENaC Causes Liddle Syndrome. J. Am. Soc. Nephrol. · 2017
- Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages. Histochem. Cell Biol. · 2017
- Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. Gene · 2016
- Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures. Am. J. Physiol. · 2013
- Structure and dynamics of human Nedd4-1 WW3 in complex with the alphaENaC PY motif. Biochim. Biophys. Acta · 2013
- Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9). J. Biol. Chem. · 2012
- Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways. Histochem. Cell Biol. · 2012
- Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. Hum. Mutat. · 2009
- Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes. J. Steroid Biochem. Mol. Biol. · 2008
- Nedd4-2 induces endocytosis and degradation of proteolytically cleaved epithelial Na+ channels. J. Biol. Chem. · 2008
- … and 25 more in the literature graph
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