SCNN1A
entrez
6337
canonical
uniprot
P37088
canonical
ensembl
ENSG00000111319
resolver
ensp
ENSP00000228916
resolver
ensp
ENSP00000353292
resolver
ensp
ENSP00000438739
resolver
genesymbol
SCNN1A
resolver
genesymbol_syn
SCNN1
resolver
hgnc
HGNC:10599
resolver
uniprot
A5X2U9
resolver
uniprot
B4E2Q5
resolver
uniprot
C5HTZ0
resolver
uniprot
O43271
resolver
uniprot
Q6GSQ6
resolver
uniprot
Q9UM64
resolver
uniprot_entry
SCNNA_HUMAN
resolver
uniprot_sec
A5X2U9
resolver
uniprot_sec
B4E2Q5
resolver
uniprot_sec
C5HTZ0
resolver
uniprot_sec
O43271
resolver
uniprot_sec
Q6GSQ6
resolver
uniprot_sec
Q9UM64
resolver
activity_regulation
ACTIVITY REGULATION: Originally identified and characterized by its inhibition by the diuretic drug amiloride (PubMed:8023962, PubMed:8278374, PubMed:9792722). Inhibited by phenamil (PubMed:8278374). {ECO:0000269|PubMed:8023962, ECO:0000269|PubMed:8278374, ECO:0000269|PubMed:9792722}.
uniprot
proteins
amino_acid_sequence
MEGNKLEEQDSSPPQSTPGLMKGNKREEQGLGPEPAAPQQPTAEEEALIEFHRSYRELFEFFCNNTTIHGAIRLVCSQHNRMKTAFWAVLWLCTFGMMYWQFGLLFGEYFSYPVSLNINLNSDKLVFPAVTICTLNPYRYPEIKEELEELDRITEQTLFDLYKYSSFTTLVAGSRSRRDLRGTLPHPLQRLRVPPPPHGARRARSVASSLRDNNPQVDWKDWKIGFQLCNQNKSDCFYQTYSSGVDAVREWYRFHYINILSRLPETLPSLEEDTLGNFIFACRFNQVSCNQANYSHFHHPMYGNCYTFNDKNNSNLWMSSMPGINNGLSLMLRAEQNDFIPLLSTVTGARVMVHGQDEPAFMDDGGFNLRPGVETSISMRKETLDRLGGDYGDCTKNGSDVPVENLYPSKYTQQVCIHSCFQESMIKECGCAYIFYPRPQNVEYCDYRKHSSWGYCYYKLQVDFSSDHLGCFTKCRKPCSVTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYTVNNKRNGVAKVNIFFKELNYKTNSESPSVTMVTLLSNLGSQWSLWFGSSVLSVVEMAELVFDLLVIMFLMLLRRFRSRYWSPGRGGRGAQEVASTLASSPPSHFCPHPMSLSLSQPGPAPSPALTAPPPAYATLGPRPSPGGSAGASSSTCPLGGP
uniprot
proteins
disease_involvement
DISEASE: Pseudohypoaldosteronism 1B1, autosomal recessive (PHA1B1) [MIM:264350]: A form of pseudohypoaldosteronism type 1, a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. The disorder affects multiple organs, and is characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss. {ECO:0000269|PubMed:10586178, ECO:0000269|PubMed:15853823, ECO:0000269|PubMed:18634878}. Note=The disease is caused by variants affecting the gene represented in this entry. 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). {ECO:0000269|PubMed:18634878}.; DISEASE: Bronchiectasis with or without elevated sweat chloride 2 (BESC2) [MIM:613021]: 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. {ECO:0000269|PubMed:19462466}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Liddle syndrome 3 (LIDLS3) [MIM:618126]: 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. {ECO:0000269|PubMed:28710092}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:30251954, PubMed:32729833, PubMed:8023962, PubMed:8278374, PubMed:9792722). 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 (PubMed:24124190, PubMed:28710092, PubMed:8278374). It plays a key role in maintaining sodium homeostasis through electrogenic sodium reabsorption in the kidneys (PubMed:12107247). Additionally, ENaC is essential for airway surface liquid homeostasis, which is crucial for proper mucus clearance (PubMed:24124190, PubMed:28710092). {ECO:0000269|PubMed:12107247, ECO:0000269|PubMed:24124190, ECO:0000269|PubMed:28710092, ECO:0000269|PubMed:30251954, ECO:0000269|PubMed:32729833, ECO:0000269|PubMed:8023962, ECO:0000269|PubMed:8278374, ECO:0000269|PubMed:9792722}.; FUNCTION: [Isoform 4]: Not functional. {ECO:0000269|PubMed:9575806}.
uniprot
proteins
mass_dalton
75704
uniprot
proteins
mutagenesis
MUTAGEN 394; /note="C->S: Increased channel activity."; /evidence="ECO:0000269|PubMed:28710092"; MUTAGEN 644; /note="Y->A: Prevents ubiquitination by NEDD4L."; /evidence="ECO:0000269|PubMed:17502380
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated. Can be ubiquitinated at multiple sites and undergo monoubiquitination and polyubiquitination. Ubiquitination by NEDD4 or NEDD4L inhibits the ENaC channel through endocytosis, intracellular retention and degradation of its individual subunits. {ECO:0000269|PubMed:11244092, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12167593, ECO:0000269|PubMed:17502380, ECO:0000269|PubMed:18174164, ECO:0000269|PubMed:23665454, ECO:0000269|PubMed:9792722}.; PTM: ENaC is activated through the proteolytic maturation of its subunits. Furin cleaves the SCNN1A subunit, which results in a stepwise increase in the open probability of the channel due to the release of an inhibitory tract (By similarity). BPIFA1, which is recruited by the SCNN1B subunit, prevents the proteolytic activation of ENaC (PubMed:24124190). {ECO:0000250|UniProtKB:Q61180, ECO:0000269|PubMed:24124190}.; PTM: N-glycosylated. {ECO:0000250|UniProtKB:P37089}.
uniprot
proteins
protein_family
Amiloride-sensitive sodium channel (TC 1.A.6) family
uniprot
proteins
protein_family
SCNN1A subfamily
uniprot
proteins
pubmed
10404817
uniprot
proteins
pubmed
10447117
uniprot
proteins
pubmed
10523338
uniprot
proteins
pubmed
10586178
uniprot
proteins
pubmed
11244092
uniprot
proteins
pubmed
11266509
uniprot
proteins
pubmed
11696533
uniprot
proteins
pubmed
12107247
uniprot
proteins
pubmed
12167593
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15734793
uniprot
proteins
pubmed
15853823
uniprot
proteins
pubmed
16207733
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17502380
uniprot
proteins
pubmed
17766193
uniprot
proteins
pubmed
18174164
uniprot
proteins
pubmed
18634878
uniprot
proteins
pubmed
1939532
uniprot
proteins
pubmed
19462466
uniprot
proteins
pubmed
22207244
uniprot
proteins
pubmed
22493497
uniprot
proteins
pubmed
23665454
uniprot
proteins
pubmed
24124190
uniprot
proteins
pubmed
26772908
uniprot
proteins
pubmed
28130590
uniprot
proteins
pubmed
28710092
uniprot
proteins
pubmed
30251954
uniprot
proteins
pubmed
32729833
uniprot
proteins
pubmed
8023962
uniprot
proteins
pubmed
8278374
uniprot
proteins
pubmed
9169421
uniprot
proteins
pubmed
9575806
uniprot
proteins
pubmed
9612219
uniprot
proteins
pubmed
9654208
uniprot
proteins
pubmed
9792722
uniprot
proteins
sequence_length
669
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:18174164, ECO:0000269|PubMed:22207244, ECO:0000269|PubMed:28130590}; Multi-pass membrane protein {ECO:0000269|PubMed:32729833}. Cell projection, cilium {ECO:0000269|PubMed:22207244}. Cytoplasmic granule {ECO:0000269|PubMed:28130590}. Cytoplasm {ECO:0000269|PubMed:28130590}. Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250|UniProtKB:P37089}. Cell projection, cilium, flagellum {ECO:0000250|UniProtKB:P37089}. Note=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). {ECO:0000250|UniProtKB:P37089, ECO:0000269|PubMed:22207244, ECO:0000269|PubMed:24124190, ECO:0000269|PubMed:28130590}.
uniprot
proteins
transmembrane_region
TRANSMEM 86..106; /note="Helical; Name=1"; /evidence="ECO:0000255"; TRANSMEM 563..583; /note="Helical; Name=2"; /evidence="ECO:0000255
uniprot
proteins