SCNNG_HUMAN
ID SCNNG_HUMAN Reviewed; 649 AA.
AC P51170; P78437; Q6PCC2; Q93023; Q93024; Q93025; Q93026; Q93027; Q96TD2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 4.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Amiloride-sensitive sodium channel subunit gamma;
DE AltName: Full=Epithelial Na(+) channel subunit gamma;
DE Short=ENaCG;
DE Short=Gamma-ENaC;
DE AltName: Full=Gamma-NaCH;
DE AltName: Full=Nonvoltage-gated sodium channel 1 subunit gamma;
DE AltName: Full=SCNEG;
GN Name=SCNN1G;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Lung;
RX PubMed=7490094; DOI=10.1006/geno.1995.1188;
RA Voilley N., Bassilana F., Mignon C., Merscher S., Mattei M.-G., Carle G.F.,
RA Lazdunski M., Barbry P.;
RT "Cloning, chromosomal localization, and physical linkage of the beta and
RT gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-
RT sensitive sodium channel.";
RL Genomics 28:560-565(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS TRP-178; PRO-502 AND SER-614, AND
RP SUBUNIT.
RC TISSUE=Kidney;
RX PubMed=7762608; DOI=10.1152/ajpcell.1995.268.5.c1157;
RA McDonald F.J., Snyder P.M., Price M.P., Welsh M.J.;
RT "Cloning and expression of the beta- and gamma-subunits of the human
RT epithelial sodium channel.";
RL Am. J. Physiol. 268:C1157-C1163(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-502.
RX PubMed=12107247; DOI=10.1210/jcem.87.7.8674;
RA Saxena A., Hanukoglu I., Saxena D., Thompson R.J., Gardiner R.M.,
RA Hanukoglu A.;
RT "Novel mutations responsible for autosomal recessive multisystem
RT pseudohypoaldosteronism and sequence variants in epithelial sodium channel
RT alpha-, beta-, and gamma-subunit genes.";
RL J. Clin. Endocrinol. Metab. 87:3344-3350(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-105; 218-269; 306-392;
RP 433-463 AND 499-515, AND VARIANT PRO-502.
RX PubMed=8824247; DOI=10.1074/jbc.271.42.26062;
RA Thomas C.P., Doggett N.A., Fisher R., Stokes J.B.;
RT "Genomic organization and the 5' flanking region of the gamma subunit of
RT the human amiloride-sensitive epithelial sodium channel.";
RL J. Biol. Chem. 271:26062-26066(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 524-649, INVOLVEMENT IN LIDLS2,
RP VARIANT LIDLS2 573-TRP--LEU-649 DEL, FUNCTION, AND CHARACTERIZATION OF
RP VARIANT LIDLS2 573-TRP--LEU-649 DEL.
RX PubMed=7550319; DOI=10.1038/ng0995-76;
RA Hansson J.H., Nelson-Williams C., Suzuki H., Schild L., Shimkets R.A.,
RA Lu Y., Canessa C.M., Iwasaki T., Rossier B.C., Lifton R.P.;
RT "Hypertension caused by a truncated epithelial sodium channel gamma
RT subunit: genetic heterogeneity of Liddle syndrome.";
RL Nat. Genet. 11:76-82(1995).
RN [7]
RP INTERACTION WITH WWP1 AND WWP2.
RX PubMed=9169421; DOI=10.1074/jbc.272.23.14611;
RA Pirozzi G., McConnell S.J., Uveges A.J., Carter J.M., Sparks A.B.,
RA Kay B.K., Fowlkes D.M.;
RT "Identification of novel human WW domain-containing proteins by cloning of
RT ligand targets.";
RL J. Biol. Chem. 272:14611-14616(1997).
RN [8]
RP INTERACTION WITH NEDD4 AND NEDD4L.
RX PubMed=11244092; DOI=10.1074/jbc.c000906200;
RA Harvey K.F., Dinudom A., Cook D.I., Kumar S.;
RT "The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial
RT sodium channel.";
RL J. Biol. Chem. 276:8597-8601(2001).
RN [9]
RP INTERACTION WITH NEDD4 AND WWP2.
RX PubMed=12167593; DOI=10.1152/ajprenal.00080.2002;
RA McDonald F.J., Western A.H., McNeil J.D., Thomas B.C., Olson D.R.,
RA Snyder P.M.;
RT "Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial
RT Na(+) channel.";
RL Am. J. Physiol. 283:F431-F436(2002).
RN [10]
RP INVOLVEMENT IN PHA1B.
RX PubMed=8640238; DOI=10.1038/ng0696-248;
RA Strautnieks S.S., Thompson R.J., Gardiner R.M., Chung E.;
RT "A novel splice-site mutation in the gamma subunit of the epithelial sodium
RT channel gene in three pseudohypoaldosteronism type 1 families.";
RL Nat. Genet. 13:248-250(1996).
RN [11]
RP INVOLVEMENT IN LIDLS2.
RX PubMed=12473862; DOI=10.1097/00004872-200212000-00017;
RA Hiltunen T.P., Hannila-Handelberg T., Petaejaeniemi N., Kantola I.,
RA Tikkanen I., Virtamo J., Gautschi I., Schild L., Kontula K.;
RT "Liddle's syndrome associated with a point mutation in the extracellular
RT domain of the epithelial sodium channel gamma subunit.";
RL J. Hypertens. 20:2383-2390(2002).
RN [12]
RP INVOLVEMENT IN LIDLS2.
RX PubMed=17634077; DOI=10.1111/j.1365-2265.2007.02967.x;
RA Wang Y., Zheng Y., Chen J., Wu H., Zheng D., Hui R.;
RT "A novel epithelial sodium channel gamma-subunit de novo frameshift
RT mutation leads to Liddle syndrome.";
RL Clin. Endocrinol. (Oxf.) 67:801-804(2007).
RN [13]
RP PROTEOLYTIC PROCESSING.
RX PubMed=18650438; DOI=10.1074/jbc.m803931200;
RA Carattino M.D., Hughey R.P., Kleyman T.R.;
RT "Proteolytic processing of the epithelial sodium channel gamma subunit has
RT a dominant role in channel activation.";
RL J. Biol. Chem. 283:25290-25295(2008).
RN [14]
RP INVOLVEMENT IN BESC3.
RX PubMed=19017867; DOI=10.1378/chest.08-2246;
RA Mutesa L., Azad A.K., Verhaeghe C., Segers K., Vanbellinghen J.F.,
RA Ngendahayo L., Rusingiza E.K., Mutwa P.R., Rulisa S., Koulischer L.,
RA Cassiman J.J., Cuppens H., Bours V.;
RT "Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms:
RT identification of novel cystic fibrosis transmembrane conductance regulator
RT and epithelial sodium channel gene variants.";
RL Chest 135:1233-1242(2009).
RN [15]
RP TISSUE SPECIFICITY.
RX PubMed=22207244; DOI=10.1007/s00418-011-0904-1;
RA Enuka Y., Hanukoglu I., Edelheit O., Vaknine H., Hanukoglu A.;
RT "Epithelial sodium channels (ENaC) are uniformly distributed on motile
RT cilia in the oviduct and the respiratory airways.";
RL Histochem. Cell Biol. 137:339-353(2012).
RN [16]
RP INTERACTION WITH PCSK9.
RX PubMed=22493497; DOI=10.1074/jbc.m112.363382;
RA Sharotri V., Collier D.M., Olson D.R., Zhou R., Snyder P.M.;
RT "Regulation of epithelial sodium channel trafficking by proprotein
RT convertase subtilisin/kexin type 9 (PCSK9).";
RL J. Biol. Chem. 287:19266-19274(2012).
RN [17]
RP PROTEOLYTIC PROCESSING, FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=24124190; DOI=10.1152/ajplung.00103.2013;
RA Hobbs C.A., Blanchard M.G., Alijevic O., Tan C.D., Kellenberger S.,
RA Bencharit S., Cao R., Kesimer M., Walton W.G., Henderson A.G.,
RA Redinbo M.R., Stutts M.J., Tarran R.;
RT "Identification of the SPLUNC1 ENaC-inhibitory domain yields novel
RT strategies to treat sodium hyperabsorption in cystic fibrosis airway
RT epithelial cultures.";
RL Am. J. Physiol. 305:L990-L1001(2013).
RN [18]
RP REVIEW.
RX PubMed=23547933; DOI=10.2174/1874467211306010005;
RA Alvarez de la Rosa D., Navarro-Gonzalez J.F., Giraldez T.;
RT "ENaC modulators and renal disease.";
RL Curr. Mol. Pharmacol. 6:35-43(2013).
RN [19]
RP PHYLOGENETIC ANALYSIS, AND NOMENCLATURE.
RX PubMed=26772908; DOI=10.1016/j.gene.2015.12.061;
RA Hanukoglu I., Hanukoglu A.;
RT "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function,
RT tissue distribution, and associated inherited diseases.";
RL Gene 579:95-132(2016).
RN [20]
RP VARIANTS TRP-178; PRO-502 AND SER-614.
RX PubMed=10404817; DOI=10.1210/jcem.84.7.5857;
RA Arai K., Zachman K., Shibasaki T., Chrousos G.P.;
RT "Polymorphisms of amiloride-sensitive sodium channel subunits in five
RT sporadic cases of pseudohypoaldosteronism: do they have pathologic
RT potential?";
RL J. Clin. Endocrinol. Metab. 84:2434-2437(1999).
RN [21]
RP VARIANTS CYS-49 AND SER-183.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-58.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [23]
RP VARIANTS SER-183 AND LYS-197, AND INVOLVEMENT IN BESC3.
RX PubMed=18507830; DOI=10.1186/1465-9921-9-46;
RA Fajac I., Viel M., Sublemontier S., Hubert D., Bienvenu T.;
RT "Could a defective epithelial sodium channel lead to bronchiectasis.";
RL Respir. Res. 9:46-46(2008).
CC -!- FUNCTION: Sodium permeable non-voltage-sensitive ion channel inhibited
CC by the diuretic amiloride. Mediates the electrodiffusion of the luminal
CC sodium (and water, which follows osmotically) through the apical
CC membrane of epithelial cells. Plays an essential role in electrolyte
CC and blood pressure homeostasis, but also in airway surface liquid
CC homeostasis, which is important for proper clearance of mucus. Controls
CC the reabsorption of sodium in kidney, colon, lung and sweat glands.
CC Also plays a role in taste perception. {ECO:0000269|PubMed:24124190,
CC ECO:0000269|PubMed:7550319, ECO:0000303|PubMed:7490094}.
CC -!- ACTIVITY REGULATION: Activated by WNK1, WNK2, WNK3 and WNK4.
CC {ECO:0000250|UniProtKB:Q9WU39}.
CC -!- SUBUNIT: Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a
CC gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in
CC some organisms and can replace the alpha/SCNN1A subunit to form an
CC alternative channel with specific properties (PubMed:7762608).
CC Interacts with NEDD4; via the WW domains (PubMed:11244092,
CC PubMed:12167593). Interacts with NEDD4L; via the WW domains
CC (PubMed:11244092). Interacts with WWP1; via the WW domains
CC (PubMed:9169421). Interacts with WWP2; via the WW domains
CC (PubMed:9169421, PubMed:12167593). Interacts with the full-length
CC immature form of PCSK9 (pro-PCSK9) (PubMed:22493497).
CC {ECO:0000269|PubMed:11244092, ECO:0000269|PubMed:12167593,
CC ECO:0000269|PubMed:22493497, ECO:0000269|PubMed:24124190,
CC ECO:0000269|PubMed:7490094, ECO:0000269|PubMed:7762608,
CC ECO:0000269|PubMed:9169421}.
CC -!- INTERACTION:
CC P51170; P37088: SCNN1A; NbExp=3; IntAct=EBI-2547354, EBI-7845444;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:24124190, ECO:0000303|PubMed:7490094}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P37089}. Note=Apical membrane
CC of epithelial cells. {ECO:0000303|PubMed:7490094}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level).
CC {ECO:0000269|PubMed:22207244}.
CC -!- PTM: Phosphorylated on serine and threonine residues. Aldosterone and
CC insulin increase the basal level of phosphorylation.
CC {ECO:0000250|UniProtKB:P37091}.
CC -!- PTM: Ubiquitinated; this targets individual subunits for endocytosis
CC and proteasome-mediated degradation. {ECO:0000250|UniProtKB:P37091}.
CC -!- PTM: ENaC cleavage by furin, and subsequently by prostasin (PRSS8),
CC leads to a stepwise increase in the open probability of the channel as
CC a result of release of the alpha and gamma subunit inhibitory tracts,
CC respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects
CC ENaC against proteolytic activation. {ECO:0000269|PubMed:18650438,
CC ECO:0000269|PubMed:24124190}.
CC -!- DISEASE: Liddle syndrome 2 (LIDLS2) [MIM:618114]: A form of Liddle
CC syndrome, an autosomal dominant disorder characterized by early onset
CC of hypertension, hypokalemic alkalosis, and suppression of plasma renin
CC activity and aldosterone secretion. {ECO:0000269|PubMed:12473862,
CC ECO:0000269|PubMed:17634077, ECO:0000269|PubMed:7550319}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Bronchiectasis with or without elevated sweat chloride 3
CC (BESC3) [MIM:613071]: A debilitating respiratory disease characterized
CC by chronic, abnormal dilatation of the bronchi and other cystic
CC fibrosis-like symptoms in the absence of known causes of bronchiectasis
CC (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common
CC variable immunodeficiency, foreign body obstruction). Clinical features
CC include sub-normal lung function, sinopulmonary infections, chronic
CC productive cough, excessive sputum production, and elevated sweat
CC chloride in some cases. {ECO:0000269|PubMed:18507830,
CC ECO:0000269|PubMed:19017867}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pseudohypoaldosteronism 1, autosomal recessive (PHA1B)
CC [MIM:264350]: A rare salt wasting disease resulting from target organ
CC unresponsiveness to mineralocorticoids. PHA1B is a severe form
CC involving multiple organ systems, and characterized by an often
CC fulminant presentation in the neonatal period with dehydration,
CC hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and
CC weight loss. {ECO:0000269|PubMed:8640238}. Note=Disease susceptibility
CC is associated with variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. SCNN1G subfamily. {ECO:0000305}.
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DR EMBL; X87160; CAA60633.1; -; mRNA.
DR EMBL; L36592; AAA75460.1; -; mRNA.
DR EMBL; AF356502; AAK50910.1; -; Genomic_DNA.
DR EMBL; AF356493; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356494; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356495; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356496; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356497; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356498; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356499; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356500; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; AF356501; AAK50910.1; JOINED; Genomic_DNA.
DR EMBL; BC059391; AAH59391.1; -; mRNA.
DR EMBL; BC069652; AAH69652.1; -; mRNA.
DR EMBL; U48936; AAC50737.1; -; mRNA.
DR EMBL; U53836; AAC50744.1; -; Genomic_DNA.
DR EMBL; U53837; AAC50745.1; -; Genomic_DNA.
DR EMBL; U53841; AAC50749.1; -; Genomic_DNA.
DR EMBL; U53844; AAC50752.1; -; Genomic_DNA.
DR EMBL; U53845; AAC50753.1; -; Genomic_DNA.
DR EMBL; U53846; AAC50754.1; -; Genomic_DNA.
DR EMBL; U53847; AAC50755.1; -; Genomic_DNA.
DR EMBL; U53850; AAC50758.1; -; Genomic_DNA.
DR EMBL; U53852; AAC50760.1; -; Genomic_DNA.
DR EMBL; U35630; AAC50217.1; -; Genomic_DNA.
DR CCDS; CCDS10608.1; -.
DR PIR; I38204; I38204.
DR PIR; I64847; I64847.
DR RefSeq; NP_001030.2; NM_001039.3.
DR PDB; 6BQN; EM; 3.90 A; C=78-524.
DR PDB; 6WTH; EM; 3.06 A; C=1-649.
DR PDBsum; 6BQN; -.
DR PDBsum; 6WTH; -.
DR AlphaFoldDB; P51170; -.
DR SMR; P51170; -.
DR BioGRID; 112244; 17.
DR ComplexPortal; CPX-2188; Amiloride-sensitive sodium channel complex, alpha-beta-gamma.
DR ComplexPortal; CPX-312; Amiloride-sensitive sodium channel complex, delta-alpha-beta-gamma.
DR ComplexPortal; CPX-313; Amiloride-sensitive sodium channel complex, delta-beta-gamma.
DR CORUM; P51170; -.
DR ELM; P51170; -.
DR IntAct; P51170; 5.
DR MINT; P51170; -.
DR STRING; 9606.ENSP00000300061; -.
DR ChEMBL; CHEMBL1628484; -.
DR DrugBank; DB00594; Amiloride.
DR DrugBank; DB14509; Lithium carbonate.
DR DrugBank; DB00384; Triamterene.
DR DrugCentral; P51170; -.
DR GuidetoPHARMACOLOGY; 741; -.
DR TCDB; 1.A.6.1.1; the epithelial na(+) channel (enac) family.
DR GlyGen; P51170; 2 sites.
DR iPTMnet; P51170; -.
DR PhosphoSitePlus; P51170; -.
DR BioMuta; SCNN1G; -.
DR DMDM; 108885072; -.
DR EPD; P51170; -.
DR MassIVE; P51170; -.
DR PaxDb; P51170; -.
DR PeptideAtlas; P51170; -.
DR PRIDE; P51170; -.
DR ProteomicsDB; 56297; -.
DR Antibodypedia; 25924; 398 antibodies from 33 providers.
DR DNASU; 6340; -.
DR Ensembl; ENST00000300061.3; ENSP00000300061.2; ENSG00000166828.3.
DR GeneID; 6340; -.
DR KEGG; hsa:6340; -.
DR MANE-Select; ENST00000300061.3; ENSP00000300061.2; NM_001039.4; NP_001030.2.
DR UCSC; uc002dlm.2; human.
DR CTD; 6340; -.
DR DisGeNET; 6340; -.
DR GeneCards; SCNN1G; -.
DR HGNC; HGNC:10602; SCNN1G.
DR HPA; ENSG00000166828; Tissue enhanced (kidney).
DR MalaCards; SCNN1G; -.
DR MIM; 264350; phenotype.
DR MIM; 600761; gene.
DR MIM; 613071; phenotype.
DR MIM; 618114; phenotype.
DR neXtProt; NX_P51170; -.
DR OpenTargets; ENSG00000166828; -.
DR Orphanet; 171876; Generalized pseudohypoaldosteronism type 1.
DR Orphanet; 60033; Idiopathic bronchiectasis.
DR Orphanet; 526; Liddle syndrome.
DR PharmGKB; PA307; -.
DR VEuPathDB; HostDB:ENSG00000166828; -.
DR eggNOG; KOG4294; Eukaryota.
DR GeneTree; ENSGT00940000160352; -.
DR HOGENOM; CLU_020415_0_0_1; -.
DR InParanoid; P51170; -.
DR OMA; MHVHESK; -.
DR OrthoDB; 686369at2759; -.
DR PhylomeDB; P51170; -.
DR TreeFam; TF330663; -.
DR PathwayCommons; P51170; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-9730628; Sensory perception of salty taste.
DR SignaLink; P51170; -.
DR SIGNOR; P51170; -.
DR BioGRID-ORCS; 6340; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; SCNN1G; human.
DR GeneWiki; SCNN1G; -.
DR GenomeRNAi; 6340; -.
DR Pharos; P51170; Tclin.
DR PRO; PR:P51170; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P51170; protein.
DR Bgee; ENSG00000166828; Expressed in renal medulla and 99 other tissues.
DR ExpressionAtlas; P51170; baseline and differential.
DR Genevisible; P51170; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0034706; C:sodium channel complex; IDA:UniProtKB.
DR GO; GO:0005216; F:ion channel activity; IMP:CACAO.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IEA:Ensembl.
DR GO; GO:0005272; F:sodium channel activity; TAS:ProtInc.
DR GO; GO:0050699; F:WW domain binding; IPI:BHF-UCL.
DR GO; GO:0071468; P:cellular response to acidic pH; IDA:ComplexPortal.
DR GO; GO:1904045; P:cellular response to aldosterone; IC:ComplexPortal.
DR GO; GO:0036254; P:cellular response to amiloride; IDA:ComplexPortal.
DR GO; GO:1904117; P:cellular response to vasopressin; IC:ComplexPortal.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IDA:ComplexPortal.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IDA:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IC:ComplexPortal.
DR GO; GO:0050914; P:sensory perception of salty taste; IC:ComplexPortal.
DR GO; GO:0050915; P:sensory perception of sour taste; IC:ComplexPortal.
DR GO; GO:0055078; P:sodium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IDA:ComplexPortal.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; TAS:ProtInc.
DR InterPro; IPR001873; ENaC.
DR InterPro; IPR004724; ENaC_chordates.
DR InterPro; IPR020903; ENaC_CS.
DR PANTHER; PTHR11690; PTHR11690; 1.
DR Pfam; PF00858; ASC; 1.
DR PRINTS; PR01078; AMINACHANNEL.
DR TIGRFAMs; TIGR00859; ENaC; 1.
DR PROSITE; PS01206; ASC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disease variant; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Sensory transduction; Sodium; Sodium channel; Sodium transport; Taste;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..649
FT /note="Amiloride-sensitive sodium channel subunit gamma"
FT /id="PRO_0000181276"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 56..76
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..541
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 542..562
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 563..649
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 49
FT /note="G -> C (in dbSNP:rs5733)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014893"
FT VARIANT 58
FT /note="G -> R (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1183385193)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036483"
FT VARIANT 178
FT /note="R -> W"
FT /evidence="ECO:0000269|PubMed:10404817,
FT ECO:0000269|PubMed:7762608"
FT /id="VAR_015842"
FT VARIANT 183
FT /note="G -> S (in a patient with bronchiectasis;
FT dbSNP:rs5736)"
FT /evidence="ECO:0000269|PubMed:10391210,
FT ECO:0000269|PubMed:18507830"
FT /id="VAR_014894"
FT VARIANT 197
FT /note="E -> K (in a patient with bronchiectasis;
FT dbSNP:rs5738)"
FT /evidence="ECO:0000269|PubMed:18507830"
FT /id="VAR_034485"
FT VARIANT 502
FT /note="A -> P"
FT /evidence="ECO:0000269|PubMed:10404817,
FT ECO:0000269|PubMed:12107247, ECO:0000269|PubMed:7762608,
FT ECO:0000269|PubMed:8824247"
FT /id="VAR_015843"
FT VARIANT 573..649
FT /note="Missing (in LIDLS2; increased sodium channel
FT activity)"
FT /evidence="ECO:0000269|PubMed:7550319"
FT /id="VAR_081180"
FT VARIANT 614
FT /note="A -> S"
FT /evidence="ECO:0000269|PubMed:10404817,
FT ECO:0000269|PubMed:7762608"
FT /id="VAR_015844"
FT CONFLICT 339
FT /note="F -> S (in Ref. 1; CAA60633)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="A -> T (in Ref. 1; CAA60633)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="Y -> S (in Ref. 1; CAA60633)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="D -> G (in Ref. 1; CAA60633)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="S -> R (in Ref. 1; CAA60633)"
FT /evidence="ECO:0000305"
FT CONFLICT 461..463
FT /note="EWT -> DGH (in Ref. 5; AAC50758)"
FT /evidence="ECO:0000305"
FT STRAND 81..90
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 111..113
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 115..128
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 201..207
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 214..221
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 222..237
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 243..249
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 253..256
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 269..271
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 272..277
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 281..287
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 301..311
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 324..329
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 340..343
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 345..357
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 366..370
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 391..406
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 432..443
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 450..452
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 459..462
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 465..469
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 474..476
FT /evidence="ECO:0007829|PDB:6WTH"
FT HELIX 477..487
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 488..491
FT /evidence="ECO:0007829|PDB:6WTH"
FT TURN 498..500
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 501..509
FT /evidence="ECO:0007829|PDB:6WTH"
FT STRAND 512..520
FT /evidence="ECO:0007829|PDB:6WTH"
SQ SEQUENCE 649 AA; 74270 MW; F67ED45F03A9BF3F CRC64;
MAPGEKIKAK IKKNLPVTGP QAPTIKELMR WYCLNTNTHG CRRIVVSRGR LRRLLWIGFT
LTAVALILWQ CALLVFSFYT VSVSIKVHFR KLDFPAVTIC NINPYKYSTV RHLLADLEQE
TREALKSLYG FPESRKRREA ESWNSVSEGK QPRFSHRIPL LIFDQDEKGK ARDFFTGRKR
KVGGSIIHKA SNVMHIESKQ VVGFQLCSND TSDCATYTFS SGINAIQEWY KLHYMNIMAQ
VPLEKKINMS YSAEELLVTC FFDGVSCDAR NFTLFHHPMH GNCYTFNNRE NETILSTSMG
GSEYGLQVIL YINEEEYNPF LVSSTGAKVI IHRQDEYPFV EDVGTEIETA MVTSIGMHLT
ESFKLSEPYS QCTEDGSDVP IRNIYNAAYS LQICLHSCFQ TKMVEKCGCA QYSQPLPPAA
NYCNYQQHPN WMYCYYQLHR AFVQEELGCQ SVCKEACSFK EWTLTTSLAQ WPSVVSEKWL
LPVLTWDQGR QVNKKLNKTD LAKLLIFYKD LNQRSIMESP ANSIEMLLSN FGGQLGLWMS
CSVVCVIEII EVFFIDFFSI IARRQWQKAK EWWAWKQAPP CPEAPRSPQG QDNPALDIDD
DLPTFNSALH LPPALGTQVP GTPPPKYNTL RLERAFSNQL TDTQMLDEL
