Human Gene SCNN1A (ENST00000360168.7) from GENCODE V44
Description: Homo sapiens sodium channel epithelial 1 subunit alpha (SCNN1A), transcript variant 2, mRNA. (from RefSeq NM_001159576) RefSeq Summary (NM_001159576): 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]. Gencode Transcript: ENST00000360168.7 Gencode Gene: ENSG00000111319.13 Transcript (Including UTRs) Position: hg38 chr12:6,346,843-6,375,224 Size: 28,382 Total Exon Count: 12 Strand: - Coding Region Position: hg38 chr12:6,347,873-6,374,960 Size: 27,088 Coding Exon Count: 12
ID:SCNNA_HUMAN DESCRIPTION: RecName: Full=Amiloride-sensitive sodium channel subunit alpha; AltName: Full=Alpha-NaCH; AltName: Full=Epithelial Na(+) channel subunit alpha; Short=Alpha-ENaC; Short=ENaCA; AltName: Full=Nonvoltage-gated sodium channel 1 subunit alpha; AltName: Full=SCNEA; FUNCTION: 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. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception. ENZYME REGULATION: Activated by WNK1, WNK2, WNK3 and WNK4 (By similarity). SUBUNIT: Probable heterotrimer containing one alpha, one beta and one gamma subunit. A delta subunit can replace the alpha subunit. Interacts with the WW domains of NEDD4, NEDD4L, WWP1 and WWP2. Interacts with the full length immature form of PCSK9 (pro-PCSK9). SUBCELLULAR LOCATION: Apical cell membrane; Multi-pass membrane protein. Note=Apical membrane of epithelial cells. TISSUE SPECIFICITY: Highly expressed in kidney and lung. Detected at intermediate levels in pancreas and liver, and at low levels in heart and placenta. Isoform 1 and isoform 2 predominate in all tissues. Expression of isoform 3, isoform 4 and isoform 5 is very low or not detectable, except in lung and heart. INDUCTION: By aldosterone. PTM: Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation (By similarity). PTM: 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. DISEASE: Defects in SCNN1A are a cause of pseudohypoaldosteronism 1, autosomal recessive (PHA1B) [MIM:264350]. 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. Note=The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878). DISEASE: Defects in SCNN1A are a cause of bronchiectasis with or without elevated sweat chloride type 2 (BESC2) [MIM:613021]; also called cystic fibrosis-like syndrome. BESC2 is 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 subnormal lung function, sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in some cases. SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily. SEQUENCE CAUTION: Sequence=AAH06526.2; Type=Erroneous initiation; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCNN1A";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P37088
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006811 ion transport GO:0006814 sodium ion transport GO:0035725 sodium ion transmembrane transport GO:0050891 multicellular organismal water homeostasis GO:0050896 response to stimulus GO:0050909 sensory perception of taste GO:0055078 sodium ion homeostasis
US Server
