TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


1.A.6.1.1
Epithelial Na+ channel, ENaC (regulates salt and fluid homeostasis and blood pressure; regulated by Nedd4 isoforms and SGK1, 2 and 3 kinases) (Henry et al., 2003; Pao 2012).  Cd2+ inhibits α-ENaC by binding to the internal pore where it interacts with residues in TMS2 (Takeda et al., 2007).  The channel is regulated by palmitoylation of the beta subunit which modulates gating (Mueller et al. 2010). ENaCs are more selective for Naa+ over other cations than ASICs (Yang and Palmer 2018). ENaC plays a role in chronic obstructive pulmonary diseases (COPD) (Zhao et al. 2014). The hetrodimeric complex can consist of αβγ or δβγ subunits, depending on the tissue (Giraldez et al. 2012).  The α- and γ-subunits of the epithelial Na+ channel interact directly with the Na+:Cl- cotransporter, NCC, in the renal distal tubule with functional cosequences, and together they determine bodily salt balance and blood pressure (Mistry et al. 2016).  ENaC is regulated by syntaxins (Saxena et al. 2006). The cryoEM structure has been solved (Noreng et al. 2018).

Accession Number:P51168
Protein Name:SCAB aka SCNN1B
Length:640
Molecular Weight:72659.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Apical cell membrane1 / Multi-pass membrane protein2
Substrate Na+

Cross database links:

Genevestigator: P51168
eggNOG: prNOG10939
HEGENOM: HBG755261
RefSeq: NP_000327.2   
Entrez Gene ID: 6338   
Pfam: PF00858   
Drugbank: Drugbank Link   
OMIM: 177200  phenotype
211400  phenotype
264350  phenotype
600760  gene
KEGG: hsa:6338   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0015280 F:amiloride-sensitive sodium channel activity
GO:0050699 F:WW domain binding
GO:0007588 P:excretion
GO:0050909 P:sensory perception of taste
GO:0006814 P:sodium ion transport

References (25)

[1] “Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel.”  Voilley N.et.al.   7490094
[2] “Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel.”  McDonald F.J.et.al.   7762608
[3] “Gene structure of the human amiloride-sensitive epithelial sodium channel beta subunit.”  Saxena A.et.al.   9813171
[4] “Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes.”  Saxena A.et.al.   12107247
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.”  Loftus B.J.et.al.   10493829
[7] “Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.”  Shimkets R.A.et.al.   7954808
[8] “Identification of novel human WW domain-containing proteins by cloning of ligand targets.”  Pirozzi G.et.al.   9169421
[9] “The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel.”  Harvey K.F.et.al.   11244092
[10] “Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel.”  McDonald F.J.et.al.   12167593
[11] “Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome.”  Hansson J.H.et.al.   7550319
[12] “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.”  Hansson J.H.et.al.   8524790
[13] “Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene.”  Tamura H.et.al.   8601645
[14] “Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1.”  Chang S.S.et.al.   8589714
[15] “Genetic analysis of the beta subunit of the epithelial Na+ channel in essential hypertension.”  Persu A.et.al.   9674649
[16] “A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel.”  Inoue J.et.al.   9626162
[17] “Genetic analysis of the epithelial sodium channel in Liddle's syndrome.”  Uehara Y.et.al.   9794716
[18] “Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?”  Arai K.et.al.   10404817
[19] “A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension.”  Rayner B.L.et.al.   12714866
[20] “Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism.”  Edelheit O.et.al.   15853823
[21] “Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome.”  Sheridan M.B.et.al.   16207733
[22] “Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit.”  Furuhashi M.et.al.   15483078
[23] “The consensus coding sequences of human breast and colorectal cancers.”  Sjoeblom T.et.al.   16959974
[24] “Could a defective epithelial sodium channel lead to bronchiectasis.”  Fajac I.et.al.   18507830
[25] “Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants.”  Mutesa L.et.al.   19017867

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
Window Size: Angle:  
FASTA formatted sequence
1:	MHVKKYLLKG LHRLQKGPGY TYKELLVWYC DNTNTHGPKR IICEGPKKKA MWFLLTLLFA 
61:	ALVCWQWGIF IRTYLSWEVS VSLSVGFKTM DFPAVTICNA SPFKYSKIKH LLKDLDELME 
121:	AVLERILAPE LSHANATRNL NFSIWNHTPL VLIDERNPHH PMVLDLFGDN HNGLTSSSAS 
181:	EKICNAHGCK MAMRLCSLNR TQCTFRNFTS ATQALTEWYI LQATNIFAQV PQQELVEMSY 
241:	PGEQMILACL FGAEPCNYRN FTSIFYPHYG NCYIFNWGMT EKALPSANPG TEFGLKLILD 
301:	IGQEDYVPFL ASTAGVRLML HEQRSYPFIR DEGIYAMSGT ETSIGVLVDK LQRMGEPYSP 
361:	CTVNGSEVPV QNFYSDYNTT YSIQACLRSC FQDHMIRNCN CGHYLYPLPR GEKYCNNRDF 
421:	PDWAHCYSDL QMSVAQRETC IGMCKESCND TQYKMTISMA DWPSEASEDW IFHVLSQERD 
481:	QSTNITLSRK GIVKLNIYFQ EFNYRTIEES AANNIVWLLS NLGGQFGFWM GGSVLCLIEF 
541:	GEIIIDFVWI TIIKLVALAK SLRQRRAQAS YAGPPPTVAE LVEAHTNFGF QPDTAPRSPN 
601:	TGPYPSEQAL PIPGTPPPNY DSLRLQPLDV IESDSEGDAI