Amiloride-sensitive sodium channel subunit beta

Details

Name
Amiloride-sensitive sodium channel subunit beta
Synonyms
  • Beta-ENaC
  • Beta-NaCH
  • ENaCB
  • Epithelial Na(+) channel subunit beta
  • Nonvoltage-gated sodium channel 1 subunit beta
  • SCNEB
Gene Name
SCNN1B
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000048|Amiloride-sensitive sodium channel subunit beta
MHVKKYLLKGLHRLQKGPGYTYKELLVWYCDNTNTHGPKRIICEGPKKKAMWFLLTLLFA
ALVCWQWGIFIRTYLSWEVSVSLSVGFKTMDFPAVTICNASPFKYSKIKHLLKDLDELME
AVLERILAPELSHANATRNLNFSIWNHTPLVLIDERNPHHPMVLDLFGDNHNGLTSSSAS
EKICNAHGCKMAMRLCSLNRTQCTFRNFTSATQALTEWYILQATNIFAQVPQQELVEMSY
PGEQMILACLFGAEPCNYRNFTSIFYPHYGNCYIFNWGMTEKALPSANPGTEFGLKLILD
IGQEDYVPFLASTAGVRLMLHEQRSYPFIRDEGIYAMSGTETSIGVLVDKLQRMGEPYSP
CTVNGSEVPVQNFYSDYNTTYSIQACLRSCFQDHMIRNCNCGHYLYPLPRGEKYCNNRDF
PDWAHCYSDLQMSVAQRETCIGMCKESCNDTQYKMTISMADWPSEASEDWIFHVLSQERD
QSTNITLSRKGIVKLNIYFQEFNYRTIEESAANNIVWLLSNLGGQFGFWMGGSVLCLIEF
GEIIIDFVWITIIKLVALAKSLRQRRAQASYAGPPPTVAELVEAHTNFGFQPDTAPRSPN
TGPYPSEQALPIPGTPPPNYDSLRLQPLDVIESDSEGDAI
Number of residues
640
Molecular Weight
72658.485
Theoretical pI
6.26
GO Classification
Functions
ligand-gated sodium channel activity / WW domain binding
Processes
excretion / ion transmembrane transport / multicellular organismal water homeostasis / regulation of sodium ion transport / response to hypoxia / sensory perception of taste / sodium ion homeostasis / sodium ion transmembrane transport / sodium ion transport / transmembrane transport / wound healing, spreading of epidermal cells
Components
apical plasma membrane / cytoplasmic vesicle 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
51-71 533-553
Cellular Location
Apical cell membrane
Gene sequence
>lcl|BSEQ0010135|Amiloride-sensitive sodium channel subunit beta (SCNN1B)
ATGCACGTGAAGAAGTACCTGCTGAAGGGCCTGCATCGGCTGCAGAAGGGCCCCGGCTAC
ACGTACAAGGAGCTGCTGGTGTGGTACTGCGACAACACCAACACCCACGGCCCCAAGCGC
ATCATCTGTGAGGGGCCCAAGAAGAAAGCCATGTGGTTCCTGCTCACCCTGCTCTTCGCC
GCCCTCGTCTGCTGGCAGTGGGGCATCTTCATCAGGACCTACTTGAGCTGGGAGGTCAGC
GTCTCCCTCTCCGTAGGCTTCAAGACCATGGACTTCCCTGCCGTCACCATCTGCAATGCT
AGCCCCTTCAAGTATTCCAAAATCAAGCATTTGCTGAAGGACCTGGATGAGCTGATGGAA
GCTGTCCTGGAGAGAATCCTGGCTCCTGAGCTAAGCCATGCCAATGCCACCAGGAACCTG
AACTTCTCCATCTGGAACCACACACCCCTGGTCCTTATTGATGAACGGAACCCCCACCAC
CCCATGGTCCTTGATCTCTTTGGAGACAACCACAATGGCTTAACAAGCAGCTCAGCATCA
GAAAAGATCTGTAATGCCCACGGGTGCAAAATGGCCATGAGACTATGTAGCCTCAACAGG
ACCCAGTGTACCTTCCGGAACTTCACCAGTGCTACCCAGGCATTGACAGAGTGGTACATC
CTGCAGGCCACCAACATCTTTGCACAGGTGCCACAGCAGGAGCTAGTAGAGATGAGCTAC
CCCGGCGAGCAGATGATCCTGGCCTGCCTATTCGGAGCTGAGCCCTGCAACTACCGGAAC
TTCACGTCCATCTTCTACCCTCACTATGGCAACTGTTACATCTTCAACTGGGGCATGACA
GAGAAGGCACTTCCTTCGGCCAACCCTGGAACTGAATTCGGCCTGAAGTTGATCCTGGAC
ATAGGCCAGGAAGACTACGTCCCCTTCCTTGCGTCCACGGCCGGGGTCAGGCTGATGCTT
CACGAGCAGAGGTCATACCCCTTCATCAGAGATGAGGGCATCTACGCCATGTCGGGGACA
GAGACGTCCATCGGGGTACTCGTGGACAAGCTTCAGCGCATGGGGGAGCCCTACAGCCCG
TGCACCGTGAATGGTTCTGAGGTCCCCGTCCAAAACTTCTACAGTGACTACAACACGACC
TACTCCATCCAGGCCTGTCTTCGCTCCTGCTTCCAAGACCACATGATCCGTAACTGCAAC
TGTGGCCACTACCTGTACCCACTGCCCCGTGGGGAGAAATACTGCAACAACCGGGACTTC
CCAGACTGGGCCCATTGCTACTCAGATCTACAGATGAGCGTGGCGCAGAGAGAGACCTGC
ATTGGCATGTGCAAGGAGTCCTGCAATGACACCCAGTACAAGATGACCATCTCCATGGCT
GACTGGCCTTCTGAGGCCTCCGAGGACTGGATTTTCCACGTCTTGTCTCAGGAGCGGGAC
CAAAGCACCAATATCACCCTGAGCAGGAAGGGAATTGTCAAGCTCAACATCTACTTCCAA
GAATTTAACTATCGCACCATTGAAGAATCAGCAGCCAATAACATCGTCTGGCTGCTCTCG
AATCTGGGTGGCCAGTTTGGCTTCTGGATGGGGGGCTCTGTGCTGTGCCTCATCGAGTTT
GGGGAGATCATCATCGACTTTGTGTGGATCACCATCATCAAGCTGGTGGCCTTGGCCAAG
AGCCTACGGCAGCGGCGAGCCCAAGCCAGCTACGCTGGCCCACCGCCCACCGTGGCCGAG
CTGGTGGAGGCCCACACCAACTTTGGCTTCCAGCCTGACACGGCCCCCCGCAGCCCCAAC
ACTGGGCCCTACCCCAGTGAGCAGGCCCTGCCCATCCCAGGCACCCCGCCCCCCAACTAT
GACTCCCTGCGTCTGCAGCCGCTGGACGTCATCGAGTCTGACAGTGAGGGTGATGCCATC
TAA
Chromosome Location
16
Locus
16p12.2-p12.1
External Identifiers
ResourceLink
UniProtKB IDP51168
UniProtKB Entry NameSCNNB_HUMAN
GenBank Protein ID1004271
GenBank Gene IDX87159
GenAtlas IDSCNN1B
HGNC IDHGNC:10600
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. [Article]
  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. [Article]
  3. Saxena A, Hanukoglu I, Strautnieks SS, Thompson RJ, Gardiner RM, Hanukoglu A: Gene structure of the human amiloride-sensitive epithelial sodium channel beta subunit. Biochem Biophys Res Commun. 1998 Nov 9;252(1):208-13. [Article]
  4. 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. [Article]
  5. 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. [Article]
  6. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. [Article]
  7. Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR Jr, Ulick S, Milora RV, Findling JW, et al.: Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994 Nov 4;79(3):407-14. [Article]
  8. Hanukoglu A: Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. J Clin Endocrinol Metab. 1991 Nov;73(5):936-44. [Article]
  9. Waldmann R, Champigny G, Bassilana F, Voilley N, Lazdunski M: Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel. J Biol Chem. 1995 Nov 17;270(46):27411-4. [Article]
  10. 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. [Article]
  11. 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. [Article]
  12. 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. [Article]
  13. Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ: Delta-subunit confers novel biophysical features to alpha beta gamma-human epithelial sodium channel (ENaC) via a physical interaction. J Biol Chem. 2006 Mar 24;281(12):8233-41. Epub 2006 Jan 19. [Article]
  14. Hanukoglu A, Edelheit O, Shriki Y, Gizewska M, Dascal N, Hanukoglu I: Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes. J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):268-74. doi: 10.1016/j.jsbmb.2008.06.013. Epub 2008 Jun 26. [Article]
  15. Edelheit O, Hanukoglu I, Shriki Y, Tfilin M, Dascal N, Gillis D, Hanukoglu A: Truncated beta epithelial sodium channel (ENaC) subunits responsible for multi-system pseudohypoaldosteronism support partial activity of ENaC. J Steroid Biochem Mol Biol. 2010 Mar;119(1-2):84-8. doi: 10.1016/j.jsbmb.2010.01.002. Epub 2010 Jan 12. [Article]
  16. 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. [Article]
  17. 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. [Article]
  18. 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. [Article]
  19. Alvarez de la Rosa D, Navarro-Gonzalez JF, Giraldez T: ENaC modulators and renal disease. Curr Mol Pharmacol. 2013 Mar;6(1):35-43. [Article]
  20. Garland AL, Walton WG, Coakley RD, Tan CD, Gilmore RC, Hobbs CA, Tripathy A, Clunes LA, Bencharit S, Stutts MJ, Betts L, Redinbo MR, Tarran R: Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):15973-8. doi: 10.1073/pnas.1311999110. Epub 2013 Sep 16. [Article]
  21. 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. [Article]
  22. Hansson JH, Schild L, Lu Y, Wilson TA, Gautschi I, Shimkets R, Nelson-Williams C, Rossier BC, Lifton RP: A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11495-9. [Article]
  23. Tamura H, Schild L, Enomoto N, Matsui N, Marumo F, Rossier BC: Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene. J Clin Invest. 1996 Apr 1;97(7):1780-4. [Article]
  24. Chang SS, Grunder S, Hanukoglu A, Rosler A, Mathew PM, Hanukoglu I, Schild L, Lu Y, Shimkets RA, Nelson-Williams C, Rossier BC, Lifton RP: Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996 Mar;12(3):248-53. [Article]
  25. Persu A, Barbry P, Bassilana F, Houot AM, Mengual R, Lazdunski M, Corvol P, Jeunemaitre X: Genetic analysis of the beta subunit of the epithelial Na+ channel in essential hypertension. Hypertension. 1998 Jul;32(1):129-37. [Article]
  26. Inoue J, Iwaoka T, Tokunaga H, Takamune K, Naomi S, Araki M, Takahama K, Yamaguchi K, Tomita K: A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel. J Clin Endocrinol Metab. 1998 Jun;83(6):2210-3. [Article]
  27. Uehara Y, Sasaguri M, Kinoshita A, Tsuji E, Kiyose H, Taniguchi H, Noda K, Ideishi M, Inoue J, Tomita K, Arakawa K: Genetic analysis of the epithelial sodium channel in Liddle's syndrome. J Hypertens. 1998 Aug;16(8):1131-5. [Article]
  28. 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. [Article]
  29. Rayner BL, Owen EP, King JA, Soule SG, Vreede H, Opie LH, Marais D, Davidson JS: A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension. J Hypertens. 2003 May;21(5):921-6. [Article]
  30. Edelheit O, Hanukoglu I, Gizewska M, Kandemir N, Tenenbaum-Rakover Y, Yurdakok M, Zajaczek S, Hanukoglu A: Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism. Clin Endocrinol (Oxf). 2005 May;62(5):547-53. [Article]
  31. Sheridan MB, Fong P, Groman JD, Conrad C, Flume P, Diaz R, Harris C, Knowles M, Cutting GR: Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome. Hum Mol Genet. 2005 Nov 15;14(22):3493-8. Epub 2005 Oct 5. [Article]
  32. Furuhashi M, Kitamura K, Adachi M, Miyoshi T, Wakida N, Ura N, Shikano Y, Shinshi Y, Sakamoto K, Hayashi M, Satoh N, Nishitani T, Tomita K, Shimamoto K: Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit. J Clin Endocrinol Metab. 2005 Jan;90(1):340-4. Epub 2004 Oct 13. [Article]
  33. 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. [Article]
  34. 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. [Article]
  35. 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. [Article]

Drug Relations

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