SCNN1A

Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]

SCNN1A

Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and eccrine sweat glands. Also plays a role in taste perception.

Biological Process cellular response to acidic pHManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process cellular response to aldosterone1 PublicationIC:ComplexPortal
Biological Process cellular response to amilorideManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process cellular response to vasopressin1 PublicationIC:ComplexPortal
Biological Process cellular sodium ion homeostasisManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process multicellular organismal water homeostasisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of blood pressure1 PublicationIC:ComplexPortal
Biological Process sensory perception of salty taste1 PublicationIC:ComplexPortal
Biological Process sensory perception of sour taste1 PublicationIC:ComplexPortal
Biological Process sodium ion homeostasisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process sodium ion import across plasma membraneManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process sodium ion transmembrane transportManual Assertion Based On ExperimentIDA:UniProtKB

Apical cell membrane
Cell projection, cilium
Cytoplasmic granule
Cytoplasm
Cytoplasmic vesicle, secretory vesicle, acrosome
Cell projection, cilium, flagellum
In the oviduct and bronchus, located on cilia in multi-ciliated cells. In endometrial non-ciliated epithelial cells, restricted to apical surfaces. In epidermis, located nearly uniformly in the cytoplasm in a granular distribution (PubMed:28130590).
In sebaceous glands, observed only in the cytoplasmic space in between the lipid vesicles (PubMed:28130590).
In eccrine sweat glands, mainly located at the apical surface of the cells facing the lumen (PubMed:28130590).
In skin, in arrector pili muscle cells and in adipocytes, located in the cytoplasm and colocalized with actin fibers (PubMed:28130590).
In spermatogonia, spermatocytes and round spermatids, located in the cytoplasm (By similarity).
Prior to spermiation, location shifts from the cytoplasm to the spermatid tail (By similarity).
In spermatozoa, localizes at the acrosome and the central region of the sperm flagellum (By similarity).

Pseudohypoaldosteronism 1, autosomal recessive (PHA1B):
A rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1B is a severe form involving multiple organ systems, and characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss.
Bronchiectasis with or without elevated sweat chloride 2 (BESC2):
A debilitating respiratory disease characterized by chronic, abnormal dilatation of the bronchi and other cystic fibrosis-like symptoms in the absence of known causes of bronchiectasis (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common variable immunodeficiency, foreign body obstruction). Clinical features include sub-normal lung function, sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in some cases.
Liddle syndrome 3 (LIDLS3):
A form of Liddle syndrome, an autosomal dominant disorder characterized by early onset of hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion.

Cytoplasmic: 1-85
Helical: 86-106
Extracellular: 107-562
Helical: 563-583
Cytoplasmic: 584-669

Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation.
ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open probability of the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects ENaC against proteolytic activation.
N-glycosylated.