P51170 (SCNNG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Amiloride-sensitive sodium channel subunit gamma

Alternative name(s):
Epithelial Na(+) channel subunit gamma
Short name=ENaCG
Short name=Gamma-ENaC
Gamma-NaCH
Nonvoltage-gated sodium channel 1 subunit gamma
SCNEG

Gene names

Name:

SCNN1G

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	649 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
Enzyme regulation	Activated by WNK1, WNK2, WNK3 and WNK4 By similarity.
Subunit structure	Probable heterotrimer containing one alpha, one beta and one gamma subunit. A delta subunit can replace the alpha subunit. Interacts with the WW domains of NEDD4, NEDD4L, WWP1 and WWP2. Ref.7 Ref.8 Ref.9
Subcellular location	Apical cell membrane; Multi-pass membrane protein. Note: Apical membrane of epithelial cells.
Post-translational modification	Phosphorylated on serine and threonine residues By similarity. Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation By similarity.
Involvement in disease	Defects in SCNN1G are a cause of Liddle syndrome (LIDDS) [MIM:177200]. It is an autosomal dominant disorder characterized by pseudoaldosteronism and hypertension associated with hypokalemic alkalosis. The disease is caused by constitutive activation of the renal epithelial sodium channel. Ref.6 Defects in SCNN1G are the cause of bronchiectasis with or without elevated sweat chloride type 3 (BESC3) [MIM:613071]. A debilitating respiratory disease characterized by chronic, abnormal dilatation of the bronchi and other cystic fibrosis-like symptoms in the absence of known causes of bronchiectasis (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common variable immunodeficiency, foreign body obstruction). Clinical features include sub-normal lung function, sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in some cases. Ref.10 Ref.14
Sequence similarities	Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1G subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Sensory transduction Sodium transport Taste Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Ionic channel Sodium channel
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	excretion Traceable author statement. Source: ProtInc sensory perception of taste Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	WW domain binding Inferred from physical interaction. Source: BHF-UCL ligand-gated sodium channel activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 649	649	Amiloride-sensitive sodium channel subunit gamma		PRO_0000181276
Regions
	Topological domain	1 – 55	55	Cytoplasmic By similarity
	Transmembrane	56 – 79	24	Helical; By similarity
	Topological domain	80 – 523	444	Extracellular By similarity
	Transmembrane	524 – 555	32	Helical; By similarity
	Topological domain	556 – 649	94	Cytoplasmic By similarity
Amino acid modifications
	Glycosylation	209	1	N-linked (GlcNAc...) Potential
	Glycosylation	248	1	N-linked (GlcNAc...) Potential
	Glycosylation	271	1	N-linked (GlcNAc...) Potential
	Glycosylation	291	1	N-linked (GlcNAc...) Potential
	Glycosylation	497	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	49	1	G → C. Ref.12 Corresponds to variant rs5733 [ dbSNP | Ensembl ].		VAR_014893
	Natural variant	58	1	G → R in a colorectal cancer sample; somatic mutation. Ref.13		VAR_036483
	Natural variant	178	1	R → W. Ref.2 Ref.11		VAR_015842
	Natural variant	183	1	G → S in a patient with bronchiectasis. Ref.12 Ref.14 Corresponds to variant rs5736 [ dbSNP | Ensembl ].		VAR_014894
	Natural variant	197	1	E → K in a patient with bronchiectasis. Ref.14 Corresponds to variant rs5738 [ dbSNP | Ensembl ].		VAR_034485
	Natural variant	502	1	A → P. Ref.2 Ref.3 Ref.5 Ref.11		VAR_015843
	Natural variant	614	1	A → S. Ref.2 Ref.11		VAR_015844
Experimental info
	Sequence conflict	339	1	F → S in CAA60633. Ref.1
	Sequence conflict	350	1	A → T in CAA60633. Ref.1
	Sequence conflict	369	1	Y → S in CAA60633. Ref.1
	Sequence conflict	375	1	D → G in CAA60633. Ref.1
	Sequence conflict	458	1	S → R in CAA60633. Ref.1
	Sequence conflict	461 – 463	3	EWT → DGH in AAC50758. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P51170 [UniParc]. Last modified May 30, 2006. Version 4. Checksum: F67ED45F03A9BF3F	FASTA	649	74,270
	10 20 30 40 50 60 MAPGEKIKAK IKKNLPVTGP QAPTIKELMR WYCLNTNTHG CRRIVVSRGR LRRLLWIGFT 70 80 90 100 110 120 LTAVALILWQ CALLVFSFYT VSVSIKVHFR KLDFPAVTIC NINPYKYSTV RHLLADLEQE 130 140 150 160 170 180 TREALKSLYG FPESRKRREA ESWNSVSEGK QPRFSHRIPL LIFDQDEKGK ARDFFTGRKR 190 200 210 220 230 240 KVGGSIIHKA SNVMHIESKQ VVGFQLCSND TSDCATYTFS SGINAIQEWY KLHYMNIMAQ 250 260 270 280 290 300 VPLEKKINMS YSAEELLVTC FFDGVSCDAR NFTLFHHPMH GNCYTFNNRE NETILSTSMG 310 320 330 340 350 360 GSEYGLQVIL YINEEEYNPF LVSSTGAKVI IHRQDEYPFV EDVGTEIETA MVTSIGMHLT 370 380 390 400 410 420 ESFKLSEPYS QCTEDGSDVP IRNIYNAAYS LQICLHSCFQ TKMVEKCGCA QYSQPLPPAA 430 440 450 460 470 480 NYCNYQQHPN WMYCYYQLHR AFVQEELGCQ SVCKEACSFK EWTLTTSLAQ WPSVVSEKWL 490 500 510 520 530 540 LPVLTWDQGR QVNKKLNKTD LAKLLIFYKD LNQRSIMESP ANSIEMLLSN FGGQLGLWMS 550 560 570 580 590 600 CSVVCVIEII EVFFIDFFSI IARRQWQKAK EWWAWKQAPP CPEAPRSPQG QDNPALDIDD 610 620 630 640 DLPTFNSALH LPPALGTQVP GTPPPKYNTL RLERAFSNQL TDTQMLDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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., Bassilana F., Mignon C., Merscher S., Mattei M.-G., Carle G.F., Lazdunski M., Barbry P. Genomics 28:560-565(1995) [PubMed: 7490094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel." McDonald F.J., Snyder P.M., Price M.P., Welsh M.J. Am. J. Physiol. 268:C1157-C1163(1995) [PubMed: 7762608] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS TRP-178; PRO-502 AND SER-614. Tissue: Kidney.
[3]	"Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes." Saxena A., Hanukoglu I., Saxena D., Thompson R.J., Gardiner R.M., Hanukoglu A. J. Clin. Endocrinol. Metab. 87:3344-3350(2002) [PubMed: 12107247] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-502.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"Genomic organization and the 5' flanking region of the gamma subunit of the human amiloride-sensitive epithelial sodium channel." Thomas C.P., Doggett N.A., Fisher R., Stokes J.B. J. Biol. Chem. 271:26062-26066(1996) [PubMed: 8824247] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-105; 218-269; 306-392; 433-463 AND 499-515, VARIANT PRO-502.
[6]	"Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome." Hansson J.H., Nelson-Williams C., Suzuki H., Schild L., Shimkets R.A., Lu Y., Canessa C.M., Iwasaki T., Rossier B.C., Lifton R.P. Nat. Genet. 11:76-82(1995) [PubMed: 7550319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 524-649, INVOLVEMENT IN LIDDS.
[7]	"Identification of novel human WW domain-containing proteins by cloning of ligand targets." Pirozzi G., McConnell S.J., Uveges A.J., Carter J.M., Sparks A.B., Kay B.K., Fowlkes D.M. J. Biol. Chem. 272:14611-14616(1997) [PubMed: 9169421] [Abstract] Cited for: INTERACTION WITH WWP1 AND WWP2.
[8]	"The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel." Harvey K.F., Dinudom A., Cook D.I., Kumar S. J. Biol. Chem. 276:8597-8601(2001) [PubMed: 11244092] [Abstract] Cited for: INTERACTION WITH NEDD4 AND NEDD4L.
[9]	"Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel." McDonald F.J., Western A.H., McNeil J.D., Thomas B.C., Olson D.R., Snyder P.M. Am. J. Physiol. 283:F431-F436(2002) [PubMed: 12167593] [Abstract] Cited for: INTERACTION WITH NEDD4 AND WWP2.
[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., Azad A.K., Verhaeghe C., Segers K., Vanbellinghen J.F., Ngendahayo L., Rusingiza E.K., Mutwa P.R., Rulisa S., Koulischer L., Cassiman J.J., Cuppens H., Bours V. Chest 135:1233-1242(2009) [PubMed: 19017867] [Abstract] Cited for: INVOLVEMENT IN BESC3.
[11]	"Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?" Arai K., Zachman K., Shibasaki T., Chrousos G.P. J. Clin. Endocrinol. Metab. 84:2434-2437(1999) [PubMed: 10404817] [Abstract] Cited for: VARIANTS TRP-178; PRO-502 AND SER-614.
[12]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed: 10391210] [Abstract] Cited for: VARIANTS CYS-49 AND SER-183.
[13]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-58.
[14]	"Could a defective epithelial sodium channel lead to bronchiectasis." Fajac I., Viel M., Sublemontier S., Hubert D., Bienvenu T. Respir. Res. 9:46-46(2008) [PubMed: 18507830] [Abstract] Cited for: VARIANTS SER-183 AND LYS-197, INVOLVEMENT IN BESC3.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X87160 mRNA. Translation: CAA60633.1. L36592 mRNA. Translation: AAA75460.1. AF356502 , AF356493, AF356494, AF356495, AF356496, AF356497, AF356498, AF356499, AF356500, AF356501 Genomic DNA. Translation: AAK50910.1. BC059391 mRNA. Translation: AAH59391.1. BC069652 mRNA. Translation: AAH69652.1. U48936 mRNA. Translation: AAC50737.1. U53836 Genomic DNA. Translation: AAC50744.1. U53837 Genomic DNA. Translation: AAC50745.1. U53841 Genomic DNA. Translation: AAC50749.1. U53844 Genomic DNA. Translation: AAC50752.1. U53845 Genomic DNA. Translation: AAC50753.1. U53846 Genomic DNA. Translation: AAC50754.1. U53847 Genomic DNA. Translation: AAC50755.1. U53850 Genomic DNA. Translation: AAC50758.1. U53852 Genomic DNA. Translation: AAC50760.1. U35630 Genomic DNA. Translation: AAC50217.1.
IPI	IPI00016450.
PIR	I38204. I64847.
RefSeq	NP_001030.2. NM_001039.3.
UniGene	Hs.371727.
3D structure databases
ProteinModelPortal	P51170.
SMR	P51170. Positions 55-548.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51170. 1 interaction.
MINT	MINT-198604.
STRING	P51170.
Protein family/group databases
TCDB	1.A.6.1.1. epithelial Na+ channel (ENaC) family.
PTM databases
PhosphoSite	P51170.
Polymorphism databases
DMDM	108885072.
Proteomic databases
PRIDE	P51170.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000300061; ENSP00000300061; ENSG00000166828.
GeneID	6340.
KEGG	hsa:6340.
UCSC	uc002dlm.1. human.
Organism-specific databases
CTD	6340.
GeneCards	GC16P023101.
H-InvDB	HIX0038623.
HGNC	HGNC:10602. SCNN1G.
MIM	177200. phenotype. 600761. gene. 613071. phenotype.
neXtProt	NX_P51170.
Orphanet	171876. Generalized pseudohypoaldosteronism type 1. 526. Liddle syndrome.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05216.
HOVERGEN	HBG058435.
InParanoid	P51170.
OMA	LCSNDTS.
OrthoDB	EOG4TQM8J.
PhylomeDB	P51170.
Gene expression databases
ArrayExpress	P51170.
Bgee	P51170.
Genevestigator	P51170.
GermOnline	ENSG00000166828. Homo sapiens.
Family and domain databases
InterPro	IPR004724. EnaC. IPR001873. Na+channel_ASC. IPR020903. Na+channel_ASC_CS. [Graphical view]
KO	K04827.
PANTHER	PTHR11690. Na+channel_ASC. 1 hit.
Pfam	PF00858. ASC. 1 hit. [Graphical view]
PRINTS	PR01078. AMINACHANNEL.
TIGRFAMs	TIGR00859. ENaC. 1 hit.
PROSITE	PS01206. ASC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00594. Amiloride. DB00384. Triamterene.
NextBio	24620.
SOURCE	Search...

Entry information

Entry name

SCNNG_HUMAN

Accession

Primary (citable) accession number: P51170
Secondary accession number(s): P78437 , Q6PCC2, Q93023, Q93024, Q93025, Q93026, Q93027, Q96TD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 30, 2006
Last modified:	January 25, 2012
This is version 118 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.