Amiloride-sensitive sodium channel subunit gamma

Details

Name
Amiloride-sensitive sodium channel subunit gamma
Synonyms
  • ENaCG
  • Epithelial Na(+) channel subunit gamma
  • Gamma-ENaC
  • Gamma-NaCH
  • Nonvoltage-gated sodium channel 1 subunit gamma
  • SCNEG
Gene Name
SCNN1G
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010348|Amiloride-sensitive sodium channel subunit gamma
MAPGEKIKAKIKKNLPVTGPQAPTIKELMRWYCLNTNTHGCRRIVVSRGRLRRLLWIGFT
LTAVALILWQCALLVFSFYTVSVSIKVHFRKLDFPAVTICNINPYKYSTVRHLLADLEQE
TREALKSLYGFPESRKRREAESWNSVSEGKQPRFSHRIPLLIFDQDEKGKARDFFTGRKR
KVGGSIIHKASNVMHIESKQVVGFQLCSNDTSDCATYTFSSGINAIQEWYKLHYMNIMAQ
VPLEKKINMSYSAEELLVTCFFDGVSCDARNFTLFHHPMHGNCYTFNNRENETILSTSMG
GSEYGLQVILYINEEEYNPFLVSSTGAKVIIHRQDEYPFVEDVGTEIETAMVTSIGMHLT
ESFKLSEPYSQCTEDGSDVPIRNIYNAAYSLQICLHSCFQTKMVEKCGCAQYSQPLPPAA
NYCNYQQHPNWMYCYYQLHRAFVQEELGCQSVCKEACSFKEWTLTTSLAQWPSVVSEKWL
LPVLTWDQGRQVNKKLNKTDLAKLLIFYKDLNQRSIMESPANSIEMLLSNFGGQLGLWMS
CSVVCVIEIIEVFFIDFFSIIARRQWQKAKEWWAWKQAPPCPEAPRSPQGQDNPALDIDD
DLPTFNSALHLPPALGTQVPGTPPPKYNTLRLERAFSNQLTDTQMLDEL
Number of residues
649
Molecular Weight
74269.62
Theoretical pI
7.54
GO Classification
Functions
ion channel activity / ligand-gated sodium channel activity / sodium channel activity / WW domain binding
Processes
excretion / ion transmembrane transport / multicellular organismal water homeostasis / response to stimulus / sensory perception of taste / sodium ion homeostasis / sodium ion transmembrane transport / sodium ion transport / transmembrane transport
Components
apical plasma membrane / external side of plasma membrane / extracellular exosome / integral component of plasma membrane / plasma membrane / sodium channel complex
General Function
Ww domain binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
56-76 542-562
Cellular Location
Apical cell membrane
Gene sequence
>lcl|BSEQ0010349|Amiloride-sensitive sodium channel subunit gamma (SCNN1G)
ATGGCACCCGGAGAGAAGATCAAAGCCAAAATCAAGAAGAATCTGCCCGTGACGGGCCCT
CAGGCGCCGACCATTAAAGAGCTGATGCGGTGGTACTGCCTCAACACCAACACCCATGGC
TGTCGCCGCATCGTGGTGTCCCGCGGCCGTCTGCGCCGCCTCCTCTGGATCGGGTTCACA
CTGACTGCCGTGGCCCTCATCCTCTGGCAGTGCGCCCTCCTCGTCTTCTCCTTCTATACT
GTCTCAGTTTCCATCAAAGTCCACTTCCGGAAGCTGGATTTTCCTGCAGTCACCATCTGC
AACATCAACCCCTACAAGTACAGCACCGTTCGCCACCTTCTAGCTGACTTGGAACAGGAG
ACCAGAGAGGCCCTGAAGTCCCTGTATGGCTTTCCAGAGTCCCGGAAGCGCCGAGAGGCG
GAGTCCTGGAACTCCGTCTCAGAGGGAAAGCAGCCTAGATTCTCCCACCGGATTCCGCTG
CTGATCTTTGATCAGGATGAGAAGGGCAAGGCCAGGGACTTCTTCACAGGGAGGAAGCGG
AAAGTCGGCGGTAGCATCATTCACAAGGCTTCAAATGTCATGCACATCGAGTCCAAGCAA
GTGGTGGGATTCCAACTGTGCTCAAATGACACCTCCGACTGTGCCACCTACACCTTCAGC
TCGGGAATCAATGCCATTCAGGAGTGGTATAAGCTACACTACATGAACATCATGGCACAG
GTGCCTCTGGAGAAGAAAATCAACATGAGCTATTCTGCTGAGGAGCTGCTGGTGACCTGC
TTCTTTGATGGAGTGTCCTGTGATGCCAGGAATTTCACGCTTTTCCACCACCCGATGCAT
GGGAATTGCTATACTTTCAACAACAGAGAAAATGAGACCATTCTCAGCACCTCCATGGGG
GGCAGCGAATATGGGCTGCAAGTCATTTTGTACATAAACGAAGAGGAATACAACCCATTC
CTCGTGTCCTCCACTGGAGCTAAGGTGATCATCCATCGGCAGGATGAGTATCCCTTCGTC
GAAGATGTGGGAACAGAGATTGAGACAGCAATGGTCACCTCTATAGGAATGCACCTGACA
GAGTCCTTCAAGCTGAGTGAGCCCTACAGTCAGTGCACGGAGGACGGGAGTGACGTGCCA
ATCAGGAACATCTACAACGCTGCCTACTCGCTCCAGATCTGCCTTCATTCATGCTTCCAG
ACAAAGATGGTGGAGAAATGTGGGTGTGCCCAGTACAGCCAGCCTCTACCTCCTGCAGCC
AACTACTGCAACTACCAGCAGCACCCCAACTGGATGTATTGTTACTACCAACTGCATCGA
GCCTTTGTCCAGGAAGAGCTGGGCTGCCAGTCTGTGTGCAAGGAAGCCTGCAGCTTTAAA
GAGTGGACACTAACCACAAGCCTGGCACAATGGCCATCTGTGGTTTCGGAGAAGTGGTTG
CTGCCTGTTCTCACTTGGGACCAAGGCCGGCAAGTAAACAAAAAGCTCAACAAGACAGAC
TTGGCCAAACTCTTGATATTCTACAAAGACCTGAACCAGAGATCCATCATGGAGAGCCCA
GCCAACAGTATTGAGATGCTTCTGTCCAACTTCGGTGGCCAGCTGGGCCTGTGGATGAGC
TGCTCTGTTGTCTGCGTCATCGAGATCATCGAGGTCTTCTTCATTGACTTCTTCTCTATC
ATTGCCCGCCGCCAGTGGCAGAAAGCCAAGGAGTGGTGGGCCTGGAAACAGGCTCCCCCA
TGTCCAGAAGCTCCCCGTAGCCCACAGGGCCAGGACAATCCAGCCCTGGATATAGACGAT
GACCTACCCACTTTCAACTCTGCTTTGCACCTGCCTCCAGCCCTAGGAACCCAAGTGCCC
GGCACACCGCCCCCCAAATACAATACCTTGCGCTTGGAGAGGGCCTTTTCCAACCAGCTC
ACAGATACCCAGATGCTGGATGAGCTCTGA
Chromosome Location
16
Locus
16p12
External Identifiers
ResourceLink
UniProtKB IDP51170
UniProtKB Entry NameSCNNG_HUMAN
GenBank Protein ID1004273
GenBank Gene IDX87160
GenAtlas IDSCNN1G
HGNC IDHGNC:10602
General References
  1. Voilley N, Bassilana F, Mignon C, Merscher S, Mattei MG, Carle GF, Lazdunski M, Barbry P: Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel. Genomics. 1995 Aug 10;28(3):560-5. [PubMed:7490094]
  2. McDonald FJ, Price MP, Snyder PM, Welsh MJ: Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel. Am J Physiol. 1995 May;268(5 Pt 1):C1157-63. [PubMed:7762608]
  3. Saxena A, Hanukoglu I, Saxena D, Thompson RJ, Gardiner RM, Hanukoglu A: Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes. J Clin Endocrinol Metab. 2002 Jul;87(7):3344-50. [PubMed:12107247]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Thomas CP, Doggett NA, Fisher R, Stokes JB: Genomic organization and the 5' flanking region of the gamma subunit of the human amiloride-sensitive epithelial sodium channel. J Biol Chem. 1996 Oct 18;271(42):26062-6. [PubMed:8824247]
  6. Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP: Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995 Sep;11(1):76-82. [PubMed:7550319]
  7. Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM: Identification of novel human WW domain-containing proteins by cloning of ligand targets. J Biol Chem. 1997 Jun 6;272(23):14611-6. [PubMed:9169421]
  8. Harvey KF, Dinudom A, Cook DI, Kumar S: The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. J Biol Chem. 2001 Mar 16;276(11):8597-601. Epub 2001 Jan 17. [PubMed:11244092]
  9. McDonald FJ, Western AH, McNeil JD, Thomas BC, Olson DR, Snyder PM: Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2002 Sep;283(3):F431-6. [PubMed:12167593]
  10. Carattino MD, Hughey RP, Kleyman TR: Proteolytic processing of the epithelial sodium channel gamma subunit has a dominant role in channel activation. J Biol Chem. 2008 Sep 12;283(37):25290-5. doi: 10.1074/jbc.M803931200. Epub 2008 Jul 23. [PubMed:18650438]
  11. Mutesa L, Azad AK, Verhaeghe C, Segers K, Vanbellinghen JF, Ngendahayo L, Rusingiza EK, Mutwa PR, Rulisa S, Koulischer L, Cassiman JJ, Cuppens H, Bours V: Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants. Chest. 2009 May;135(5):1233-42. doi: 10.1378/chest.08-2246. Epub 2008 Nov 18. [PubMed:19017867]
  12. Enuka Y, Hanukoglu I, Edelheit O, Vaknine H, Hanukoglu A: Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways. Histochem Cell Biol. 2012 Mar;137(3):339-53. doi: 10.1007/s00418-011-0904-1. Epub 2011 Dec 30. [PubMed:22207244]
  13. Sharotri V, Collier DM, Olson DR, Zhou R, Snyder PM: Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9). J Biol Chem. 2012 Jun 1;287(23):19266-74. doi: 10.1074/jbc.M112.363382. Epub 2012 Apr 9. [PubMed:22493497]
  14. Hobbs CA, Blanchard MG, Alijevic O, Tan CD, Kellenberger S, Bencharit S, Cao R, Kesimer M, Walton WG, Henderson AG, Redinbo MR, Stutts MJ, Tarran R: Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures. Am J Physiol Lung Cell Mol Physiol. 2013 Dec;305(12):L990-L1001. doi: 10.1152/ajplung.00103.2013. Epub 2013 Oct 11. [PubMed:24124190]
  15. Alvarez de la Rosa D, Navarro-Gonzalez JF, Giraldez T: ENaC modulators and renal disease. Curr Mol Pharmacol. 2013 Mar;6(1):35-43. [PubMed:23547933]
  16. Arai K, Zachman K, Shibasaki T, Chrousos GP: Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential? J Clin Endocrinol Metab. 1999 Jul;84(7):2434-7. [PubMed:10404817]
  17. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [PubMed:10391210]
  18. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974]
  19. Fajac I, Viel M, Sublemontier S, Hubert D, Bienvenu T: Could a defective epithelial sodium channel lead to bronchiectasis. Respir Res. 2008 May 28;9:46. doi: 10.1186/1465-9921-9-46. [PubMed:18507830]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00594AmilorideapprovedyesinhibitorDetails
DB00384TriamtereneapprovedyesinhibitorDetails
DB14509Lithium carbonateapprovedunknownDetails