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 24-JAN-2024, entry version 213. 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 PHA1B3. 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 1B3, autosomal recessive (PHA1B3) CC [MIM:620126]: A form of pseudohypoaldosteronism type 1, a rare salt CC wasting disease resulting from target organ unresponsiveness to CC mineralocorticoids. The disorder affects multiple organs, and is CC characterized by an often fulminant presentation in the neonatal period CC with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, CC failure to thrive and weight loss. {ECO:0000269|PubMed:8640238}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel CC (TC 1.A.6) family. SCNN1G subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-21896; -. DR EMDB; EMD-7130; -. DR SMR; P51170; -. DR BioGRID; 112244; 18. 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 GlyCosmos; P51170; 2 sites, No reported glycans. 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; 9606-ENSP00000300061; -. DR PeptideAtlas; P51170; -. DR Antibodypedia; 25924; 437 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 AGR; HGNC:10602; -. 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; 600761; gene. DR MIM; 613071; phenotype. DR MIM; 618114; phenotype. DR MIM; 620126; 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; SCDSRNF; -. DR OrthoDB; 5344287at2759; -. 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 1157 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 cell types or tissues. DR ExpressionAtlas; P51170; baseline and differential. 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:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0034706; C:sodium channel complex; IDA:UniProtKB. DR GO; GO:0015280; F:ligand-gated sodium channel activity; IEA:Ensembl. DR GO; GO:0005216; F:monoatomic ion channel activity; IMP:CACAO. 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; NAS:ComplexPortal. DR GO; GO:1904117; P:cellular response to vasopressin; NAS:ComplexPortal. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; IDA:ComplexPortal. DR GO; GO:0050891; P:multicellular organismal-level water homeostasis; IDA:UniProtKB. DR GO; GO:0008217; P:regulation of blood pressure; NAS:ComplexPortal. DR GO; GO:0050914; P:sensory perception of salty taste; NAS:ComplexPortal. DR GO; GO:0050915; P:sensory perception of sour taste; NAS: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 Gene3D; 2.60.470.10; Acid-sensing ion channels like domains; 1. DR Gene3D; 1.10.287.770; YojJ-like; 1. DR InterPro; IPR001873; ENaC. DR InterPro; IPR004724; ENaC_chordates. DR InterPro; IPR020903; ENaC_CS. DR NCBIfam; TIGR00859; ENaC; 1. DR PANTHER; PTHR11690:SF19; AMILORIDE-SENSITIVE SODIUM CHANNEL SUBUNIT GAMMA; 1. DR PANTHER; PTHR11690; AMILORIDE-SENSITIVE SODIUM CHANNEL-RELATED; 1. DR Pfam; PF00858; ASC; 1. DR PRINTS; PR01078; AMINACHANNEL. DR PROSITE; PS01206; ASC; 1. DR Genevisible; P51170; HS. 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 //