Showing Protein Amiloride-sensitive sodium channel subunit alpha (HMDBP02267)

• 7752

1. Alpha-ENaC
2. Alpha-NaCH
3. ENaCA
4. Epithelial Na(+) channel subunit alpha
5. Nonvoltage-gated sodium channel 1 subunit alpha
6. SCNEA

• Amiloride Action Pathway
• Bendroflumethiazide Action Pathway
• Blue diaper syndrome
• Bumetanide Action Pathway
• Chlorothiazide Action Pathway
• Chlorthalidone Action Pathway
• Cyclothiazide Action Pathway
• Cystinuria
• Eplerenone Action Pathway
• Ethacrynic Acid Action Pathway
• Furosemide Action Pathway
• Glucose Transporter Defect (SGLT2)
• Hartnup Disorder
• Hydrochlorothiazide Action Pathway
• Hydroflumethiazide Action Pathway
• Iminoglycinuria
• Indapamide Action Pathway
• Kidney Function
• Lysinuric Protein Intolerance
• Lysinuric protein intolerance (LPI)
• Methyclothiazide Action Pathway
• Metolazone Action Pathway
• Polythiazide Action Pathway
• Quinethazone Action Pathway
• Spironolactone Action Pathway
• Torsemide Action Pathway
• Triamterene Action Pathway
• Trichlormethiazide Action Pathway

1. Multi-pass membrane protein
2. Apical cell membrane

>2010 bp
ATGGAGGGGAACAAGCTGGAGGAGCAGGACTCTAGCCCTCCACAGTCCACTCCAGGGCTC
ATGAAGGGGAACAAGCGTGAGGAGCAGGGGCTGGGCCCCGAACCTGCGGCGCCCCAGCAG
CCCACGGCGGAGGAGGAGGCCCTGATCGAGTTCCACCGCTCCTACCGAGAGCTCTTCGAG
TTCTTCTGCAACAACACCACCATCCACGGCGCCATCCGCCTGGTGTGCTCCCAGCACAAC
CGCATGAAGACGGCCTTCTGGGCAGTGCTGTGGCTCTGCACCTTTGGCATGATGTACTGG
CAATTCGGCCTGCTTTTCGGAGAGTACTTCAGCTACCCCGTCAGCCTCAACATCAACCTC
AACTCGGACAAGCTCGTCTTCCCCGCAGTGACCATCTGCACCCTCAATCCCTACAGGTAC
CCGGAAATTAAAGAGGAGCTGGAGGAGCTGGACCGCATCACAGAGCAGACGCTCTTTGAC
CTGTACAAATACAGCTCCTTCACCACTCTCGTGGCCGGCTCCCGCAGCCGTCGCGACCTG
CGGGGGACTCTGCCGCACCCCTTGCAGCGCCTGAGGGTCCCGCCCCCGCCTCACGGGGCC
CGTCGAGCCCGTAGCGTGGCCTCCAGCTTGCGGGACAACAACCCCCAGGTGGACTGGAAG
GACTGGAAGATCGGCTTCCAGCTGTGCAACCAGAACAAATCGGACTGCTTCTACCAGACA
TACTCATCAGGGGTGGATGCGGTGAGGGAGTGGTACCGCTTCCACTACATCAACATCCTG
TCGAGGCTGCCAGAGACTCTGCCATCCCTGGAGGAGGACACGCTGGGCAACTTCATCTTC
GCCTGCCGCTTCAACCAGGTCTCCTGCAACCAGGCGAATTACTCTCACTTCCACCACCCG
ATGTATGGAAACTGCTATACTTTCAATGACAAGAACAACTCCAACCTCTGGATGTCTTCC
ATGCCTGGAATCAACAACGGTCTGTCCCTGATGCTGCGCGCAGAGCAGAATGACTTCATT
CCCCTGCTGTCCACAGTGACTGGGGCCCGGGTAATGGTGCACGGGCAGGATGAACCTGCC
TTTATGGATGATGGTGGCTTTAACTTGCGGCCTGGCGTGGAGACCTCCATCAGCATGAGG
AAGGAAACCCTGGACAGACTTGGGGGCGATTATGGCGACTGCACCAAGAATGGCAGTGAT
GTTCCTGTTGAGAACCTTTACCCTTCAAAGTACACACAGCAGGTGTGTATTCACTCCTGC
TTCCAGGAGAGCATGATCAAGGAGTGTGGCTGTGCCTACATCTTCTATCCGCGGCCCCAG
AACGTGGAGTACTGTGACTACAGAAAGCACAGTTCCTGGGGGTACTGCTACTATAAGCTC
CAGGTTGACTTCTCCTCAGACCACCTGGGCTGTTTCACCAAGTGCCGGAAGCCATGCAGC
GTGACCAGCTACCAGCTCTCTGCTGGTTACTCACGATGGCCCTCGGTGACATCCCAGGAA
TGGGTCTTCCAGATGCTATCGCGACAGAACAATTACACCGTCAACAACAAGAGAAATGGA
GTGGCCAAAGTCAACATCTTCTTCAAGGAGCTGAACTACAAAACCAATTCTGAGTCTCCC
TCTGTCACGATGGTCACCCTCCTGTCCAACCTGGGCAGCCAGTGGAGCCTGTGGTTCGGC
TCCTCGGTGTTGTCTGTGGTGGAGATGGCTGAGCTCGTCTTTGACCTGCTGGTCATCATG
TTCCTCATGCTGCTCCGAAGGTTCCGAAGCCGATACTGGTCTCCAGGCCGAGGGGGCAGG
GGTGCTCAGGAGGTAGCCTCCACCCTGGCATCCTCCCCTCCTTCCCACTTCTGCCCCCAC
CCCATGTCTCTGTCCTTGTCCCAGCCAGGCCCTGCTCCCTCTCCAGCCTTGACAGCCCCT
CCCCCTGCCTATGCCACCCTGGGCCCCCGCCCATCTCCAGGGGGCTCTGCAGGGGCCAGT
TCCTCCACCTGTCCTCTGGGGGGGCCCTGA

• ASC (PF00858 )

• None

• 86-106
• 563-583

>Amiloride-sensitive sodium channel subunit alpha
MEGNKLEEQDSSPPQSTPGLMKGNKREEQGLGPEPAAPQQPTAEEEALIEFHRSYRELFE
FFCNNTTIHGAIRLVCSQHNRMKTAFWAVLWLCTFGMMYWQFGLLFGEYFSYPVSLNINL
NSDKLVFPAVTICTLNPYRYPEIKEELEELDRITEQTLFDLYKYSSFTTLVAGSRSRRDL
RGTLPHPLQRLRVPPPPHGARRARSVASSLRDNNPQVDWKDWKIGFQLCNQNKSDCFYQT
YSSGVDAVREWYRFHYINILSRLPETLPSLEEDTLGNFIFACRFNQVSCNQANYSHFHHP
MYGNCYTFNDKNNSNLWMSSMPGINNGLSLMLRAEQNDFIPLLSTVTGARVMVHGQDEPA
FMDDGGFNLRPGVETSISMRKETLDRLGGDYGDCTKNGSDVPVENLYPSKYTQQVCIHSC
FQESMIKECGCAYIFYPRPQNVEYCDYRKHSSWGYCYYKLQVDFSSDHLGCFTKCRKPCS
VTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYTVNNKRNGVAKVNIFFKELNYKTNSESP
SVTMVTLLSNLGSQWSLWFGSSVLSVVEMAELVFDLLVIMFLMLLRRFRSRYWSPGRGGR
GAQEVASTLASSPPSHFCPHPMSLSLSQPGPAPSPALTAPPPAYATLGPRPSPGGSAGAS
SSTCPLGGP

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2. Snyder PM, Olson DR, Thomas BC: Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. J Biol Chem. 2002 Jan 4;277(1):5-8. Epub 2001 Nov 5. [PubMed:11696533 ]
3. Voilley N, Lingueglia E, Champigny G, Mattei MG, Waldmann R, Lazdunski M, Barbry P: The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):247-51. [PubMed:8278374 ]
4. McDonald FJ, Snyder PM, McCray PB Jr, Welsh MJ: Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channel. Am J Physiol. 1994 Jun;266(6 Pt 1):L728-34. [PubMed:8023962 ]
5. Ludwig M, Bolkenius U, Wickert L, Marynen P, Bidlingmaier F: Structural organisation of the gene encoding the alpha-subunit of the human amiloride-sensitive epithelial sodium channel. Hum Genet. 1998 May;102(5):576-81. [PubMed:9654208 ]
6. Chow YH, Wang Y, Plumb J, O'Brodovich H, Hu J: Hormonal regulation and genomic organization of the human amiloride-sensitive epithelial sodium channel alpha subunit gene. Pediatr Res. 1999 Aug;46(2):208-14. [PubMed:10447117 ]
7. Bangel N, Dahlhoff C, Sobczak K, Weber WM, Kusche-Vihrog K: Upregulated expression of ENaC in human CF nasal epithelium. J Cyst Fibros. 2008 May;7(3):197-205. Epub 2007 Sep 4. [PubMed:17766193 ]
8. Thomas CP, Auerbach S, Stokes JB, Volk KA: 5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins. Am J Physiol. 1998 May;274(5 Pt 1):C1312-23. [PubMed:9612219 ]
9. Mick VE, Itani OA, Loftus RW, Husted RF, Schmidt TJ, Thomas CP: The alpha-subunit of the epithelial sodium channel is an aldosterone-induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5'-flanking region of the gene. Mol Endocrinol. 2001 Apr;15(4):575-88. [PubMed:11266509 ]
10. Tucker JK, Tamba K, Lee YJ, Shen LL, Warnock DG, Oh Y: Cloning and functional studies of splice variants of the alpha-subunit of the amiloride-sensitive Na+ channel. Am J Physiol. 1998 Apr;274(4 Pt 1):C1081-9. [PubMed:9575806 ]
11. 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 ]
12. 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 ]
13. 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 ]
14. Ambrosius WT, Bloem LJ, Zhou L, Rebhun JF, Snyder PM, Wagner MA, Guo C, Pratt JH: Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension. Hypertension. 1999 Oct;34(4 Pt 1):631-7. [PubMed:10523338 ]
15. 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 ]
16. Schaedel C, Marthinsen L, Kristoffersson AC, Kornfalt R, Nilsson KO, Orlenius B, Holmberg L: Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel. J Pediatr. 1999 Dec;135(6):739-45. [PubMed:10586178 ]
17. 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 ]
18. Hsieh K, Lalouschek W, Schillinger M, Endler G, Reisinger M, Janisiw M, Lang W, Cheng S, Wagner O, Mannhalter C: Impact of alphaENaC polymorphisms on the risk of ischemic cerebrovascular events: a multicenter case-control study. Clin Chem. 2005 Jun;51(6):952-6. Epub 2005 Feb 25. [PubMed:15734793 ]
19. 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. [PubMed:15853823 ]
20. 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. [PubMed:16207733 ]
21. Azad AK, Rauh R, Vermeulen F, Jaspers M, Korbmacher J, Boissier B, Bassinet L, Fichou Y, des Georges M, Stanke F, De Boeck K, Dupont L, Balascakova M, Hjelte L, Lebecque P, Radojkovic D, Castellani C, Schwartz M, Stuhrmann M, Schwarz M, Skalicka V, de Monestrol I, Girodon E, Ferec C, Claustres M, Tummler B, Cassiman JJ, Korbmacher C, Cuppens H: Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. Hum Mutat. 2009 Jul;30(7):1093-103. doi: 10.1002/humu.21011. [PubMed:19462466 ]