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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:P51170
Protein Name:SCAG aka SCNN1G
Length:649
Molecular Weight:74270.00
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: P51170
eggNOG: prNOG05216
RefSeq: NP_001030.2   
Entrez Gene ID: 6340   
Pfam: PF00858   
Drugbank: Drugbank Link   
OMIM: 177200  phenotype
600761  gene
613071  phenotype
KEGG: hsa:6340   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0005887 C:integral to 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 (14)

[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] “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
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Genomic organization and the 5' flanking region of the gamma subunit of the human amiloride-sensitive epithelial sodium channel.”  Thomas C.P.et.al.   8824247
[6] “Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome.”  Hansson J.H.et.al.   7550319
[7] “Identification of novel human WW domain-containing proteins by cloning of ligand targets.”  Pirozzi G.et.al.   9169421
[8] “The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel.”  Harvey K.F.et.al.   11244092
[9] “Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel.”  McDonald F.J.et.al.   12167593
[10] “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
[11] “Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?”  Arai K.et.al.   10404817
[12] “Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.”  Halushka M.K.et.al.   10391210
[13] “The consensus coding sequences of human breast and colorectal cancers.”  Sjoeblom T.et.al.   16959974
[14] “Could a defective epithelial sodium channel lead to bronchiectasis.”  Fajac I.et.al.   18507830

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)
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FASTA formatted sequence
1:	MAPGEKIKAK IKKNLPVTGP QAPTIKELMR WYCLNTNTHG CRRIVVSRGR LRRLLWIGFT 
61:	LTAVALILWQ CALLVFSFYT VSVSIKVHFR KLDFPAVTIC NINPYKYSTV RHLLADLEQE 
121:	TREALKSLYG FPESRKRREA ESWNSVSEGK QPRFSHRIPL LIFDQDEKGK ARDFFTGRKR 
181:	KVGGSIIHKA SNVMHIESKQ VVGFQLCSND TSDCATYTFS SGINAIQEWY KLHYMNIMAQ 
241:	VPLEKKINMS YSAEELLVTC FFDGVSCDAR NFTLFHHPMH GNCYTFNNRE NETILSTSMG 
301:	GSEYGLQVIL YINEEEYNPF LVSSTGAKVI IHRQDEYPFV EDVGTEIETA MVTSIGMHLT 
361:	ESFKLSEPYS QCTEDGSDVP IRNIYNAAYS LQICLHSCFQ TKMVEKCGCA QYSQPLPPAA 
421:	NYCNYQQHPN WMYCYYQLHR AFVQEELGCQ SVCKEACSFK EWTLTTSLAQ WPSVVSEKWL 
481:	LPVLTWDQGR QVNKKLNKTD LAKLLIFYKD LNQRSIMESP ANSIEMLLSN FGGQLGLWMS 
541:	CSVVCVIEII EVFFIDFFSI IARRQWQKAK EWWAWKQAPP CPEAPRSPQG QDNPALDIDD 
601:	DLPTFNSALH LPPALGTQVP GTPPPKYNTL RLERAFSNQL TDTQMLDEL