P51170 · SCNNG_HUMAN
- ProteinAmiloride-sensitive sodium channel subunit gamma
- GeneSCNN1G
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids649 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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. 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 sweat glands. Also plays a role in taste perception.
Activity regulation
Activated by WNK1, WNK2, WNK3 and WNK4.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameAmiloride-sensitive sodium channel subunit gamma
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP51170
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Multi-pass membrane protein
Note: Apical membrane of epithelial cells.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-55 | Cytoplasmic | ||||
Sequence: MAPGEKIKAKIKKNLPVTGPQAPTIKELMRWYCLNTNTHGCRRIVVSRGRLRRLL | ||||||
Transmembrane | 56-76 | Helical; Name=1 | ||||
Sequence: WIGFTLTAVALILWQCALLVF | ||||||
Topological domain | 77-541 | Extracellular | ||||
Sequence: SFYTVSVSIKVHFRKLDFPAVTICNINPYKYSTVRHLLADLEQETREALKSLYGFPESRKRREAESWNSVSEGKQPRFSHRIPLLIFDQDEKGKARDFFTGRKRKVGGSIIHKASNVMHIESKQVVGFQLCSNDTSDCATYTFSSGINAIQEWYKLHYMNIMAQVPLEKKINMSYSAEELLVTCFFDGVSCDARNFTLFHHPMHGNCYTFNNRENETILSTSMGGSEYGLQVILYINEEEYNPFLVSSTGAKVIIHRQDEYPFVEDVGTEIETAMVTSIGMHLTESFKLSEPYSQCTEDGSDVPIRNIYNAAYSLQICLHSCFQTKMVEKCGCAQYSQPLPPAANYCNYQQHPNWMYCYYQLHRAFVQEELGCQSVCKEACSFKEWTLTTSLAQWPSVVSEKWLLPVLTWDQGRQVNKKLNKTDLAKLLIFYKDLNQRSIMESPANSIEMLLSNFGGQLGLWMSC | ||||||
Transmembrane | 542-562 | Helical; Name=2 | ||||
Sequence: SVVCVIEIIEVFFIDFFSIIA | ||||||
Topological domain | 563-649 | Cytoplasmic | ||||
Sequence: RRQWQKAKEWWAWKQAPPCPEAPRSPQGQDNPALDIDDDLPTFNSALHLPPALGTQVPGTPPPKYNTLRLERAFSNQLTDTQMLDEL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Liddle syndrome 2 (LIDLS2)
- Note
- DescriptionA 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.
- See alsoMIM:618114
Natural variants in LIDLS2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081180 | 573-649 | missing | in LIDLS2; increased sodium channel activity |
Bronchiectasis with or without elevated sweat chloride 3 (BESC3)
- Note
- DescriptionA 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.
- See alsoMIM:613071
Pseudohypoaldosteronism 1B3, autosomal recessive (PHA1B3)
- Note
- DescriptionA 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.
- See alsoMIM:620126
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_014893 | 49 | in dbSNP:rs5733 | |||
Sequence: G → C | ||||||
Natural variant | VAR_036483 | 58 | in a colorectal cancer sample; somatic mutation; dbSNP:rs1183385193 | |||
Sequence: G → R | ||||||
Natural variant | VAR_015842 | 178 | ||||
Sequence: R → W | ||||||
Natural variant | VAR_014894 | 183 | in a patient with bronchiectasis; dbSNP:rs5736 | |||
Sequence: G → S | ||||||
Natural variant | VAR_034485 | 197 | in a patient with bronchiectasis; dbSNP:rs5738 | |||
Sequence: E → K | ||||||
Natural variant | VAR_015843 | 502 | ||||
Sequence: A → P | ||||||
Natural variant | VAR_081180 | 573-649 | in LIDLS2; increased sodium channel activity | |||
Sequence: Missing | ||||||
Natural variant | VAR_015844 | 614 | ||||
Sequence: A → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 750 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000181276 | 1-649 | Amiloride-sensitive sodium channel subunit gamma | |||
Sequence: MAPGEKIKAKIKKNLPVTGPQAPTIKELMRWYCLNTNTHGCRRIVVSRGRLRRLLWIGFTLTAVALILWQCALLVFSFYTVSVSIKVHFRKLDFPAVTICNINPYKYSTVRHLLADLEQETREALKSLYGFPESRKRREAESWNSVSEGKQPRFSHRIPLLIFDQDEKGKARDFFTGRKRKVGGSIIHKASNVMHIESKQVVGFQLCSNDTSDCATYTFSSGINAIQEWYKLHYMNIMAQVPLEKKINMSYSAEELLVTCFFDGVSCDARNFTLFHHPMHGNCYTFNNRENETILSTSMGGSEYGLQVILYINEEEYNPFLVSSTGAKVIIHRQDEYPFVEDVGTEIETAMVTSIGMHLTESFKLSEPYSQCTEDGSDVPIRNIYNAAYSLQICLHSCFQTKMVEKCGCAQYSQPLPPAANYCNYQQHPNWMYCYYQLHRAFVQEELGCQSVCKEACSFKEWTLTTSLAQWPSVVSEKWLLPVLTWDQGRQVNKKLNKTDLAKLLIFYKDLNQRSIMESPANSIEMLLSNFGGQLGLWMSCSVVCVIEIIEVFFIDFFSIIARRQWQKAKEWWAWKQAPPCPEAPRSPQGQDNPALDIDDDLPTFNSALHLPPALGTQVPGTPPPKYNTLRLERAFSNQLTDTQMLDEL | ||||||
Glycosylation | 209 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 497 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Phosphorylated on serine and threonine residues. Aldosterone and insulin increase the basal level of phosphorylation.
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in kidney (at protein level).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in some organisms and can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties (PubMed:7762608).
Interacts with NEDD4; via the WW domains (PubMed:11244092, PubMed:12167593).
Interacts with NEDD4L; via the WW domains (PubMed:11244092).
Interacts with WWP1; via the WW domains (PubMed:9169421).
Interacts with WWP2; via the WW domains (PubMed:12167593, PubMed:9169421).
Interacts with the full-length immature form of PCSK9 (pro-PCSK9) (PubMed:22493497).
Interacts with NEDD4; via the WW domains (PubMed:11244092, PubMed:12167593).
Interacts with NEDD4L; via the WW domains (PubMed:11244092).
Interacts with WWP1; via the WW domains (PubMed:9169421).
Interacts with WWP2; via the WW domains (PubMed:12167593, PubMed:9169421).
Interacts with the full-length immature form of PCSK9 (pro-PCSK9) (PubMed:22493497).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P51170 | SCNN1A P37088 | 3 | EBI-2547354, EBI-7845444 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length649
- Mass (Da)74,270
- Last updated2006-05-30 v4
- ChecksumF67ED45F03A9BF3F
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 339 | in Ref. 1; CAA60633 | ||||
Sequence: F → S | ||||||
Sequence conflict | 350 | in Ref. 1; CAA60633 | ||||
Sequence: A → T | ||||||
Sequence conflict | 369 | in Ref. 1; CAA60633 | ||||
Sequence: Y → S | ||||||
Sequence conflict | 375 | in Ref. 1; CAA60633 | ||||
Sequence: D → G | ||||||
Sequence conflict | 458 | in Ref. 1; CAA60633 | ||||
Sequence: S → R | ||||||
Sequence conflict | 461-463 | in Ref. 5; AAC50758 | ||||
Sequence: EWT → DGH |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X87160 EMBL· GenBank· DDBJ | CAA60633.1 EMBL· GenBank· DDBJ | mRNA | ||
L36592 EMBL· GenBank· DDBJ | AAA75460.1 EMBL· GenBank· DDBJ | mRNA | ||
AF356502 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356493 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356494 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356495 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356496 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356497 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356498 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356499 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356500 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF356501 EMBL· GenBank· DDBJ | AAK50910.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC059391 EMBL· GenBank· DDBJ | AAH59391.1 EMBL· GenBank· DDBJ | mRNA | ||
BC069652 EMBL· GenBank· DDBJ | AAH69652.1 EMBL· GenBank· DDBJ | mRNA | ||
U48936 EMBL· GenBank· DDBJ | AAC50737.1 EMBL· GenBank· DDBJ | mRNA | ||
U53836 EMBL· GenBank· DDBJ | AAC50744.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53837 EMBL· GenBank· DDBJ | AAC50745.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53841 EMBL· GenBank· DDBJ | AAC50749.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53844 EMBL· GenBank· DDBJ | AAC50752.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53845 EMBL· GenBank· DDBJ | AAC50753.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53846 EMBL· GenBank· DDBJ | AAC50754.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53847 EMBL· GenBank· DDBJ | AAC50755.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53850 EMBL· GenBank· DDBJ | AAC50758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U53852 EMBL· GenBank· DDBJ | AAC50760.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U35630 EMBL· GenBank· DDBJ | AAC50217.1 EMBL· GenBank· DDBJ | Genomic DNA |