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P51170 (SCNNG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length649 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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. Ref.13

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. Interacts with the full length immature form of PCSK9 (pro-PCSK9) By similarity. Ref.7 Ref.8 Ref.9 Ref.12 Ref.13

Subcellular location

Apical cell membrane; Multi-pass membrane protein. Note: Apical membrane of epithelial cells. Ref.13

Post-translational modification

Phosphorylated on serine and threonine residues By similarity.

Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation By similarity.

ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open probability of the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects ENaC against proteolytic activation.

Involvement in disease

Liddle syndrome (LIDDS) [MIM:177200]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Bronchiectasis with or without elevated sweat chloride 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.18

Sequence similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1G subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Sensory transduction
Sodium transport
Taste
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processexcretion

Traceable author statement PubMed 8640238. Source: ProtInc

ion transmembrane transport

Traceable author statement. Source: Reactome

multicellular organismal water homeostasis

Inferred from direct assay Ref.13. Source: UniProtKB

response to stimulus

Inferred from electronic annotation. Source: UniProtKB-KW

sensory perception of taste

Inferred from electronic annotation. Source: UniProtKB-KW

sodium ion homeostasis

Inferred from direct assay Ref.13. Source: UniProtKB

sodium ion transmembrane transport

Inferred from direct assay Ref.13. Source: UniProtKB

sodium ion transport

Traceable author statement PubMed 8521520. Source: ProtInc

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 15326289. Source: UniProt

integral component of plasma membrane

Inferred from direct assay Ref.13. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

sodium channel complex

Inferred from direct assay Ref.13. Source: UniProtKB

   Molecular_functionWW domain binding

Inferred from physical interaction PubMed 10642508. Source: BHF-UCL

ligand-gated sodium channel activity

Traceable author statement PubMed 8640238. Source: ProtInc

sodium channel activity

Traceable author statement PubMed 8521520. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 649649Amiloride-sensitive sodium channel subunit gamma
PRO_0000181276

Regions

Topological domain1 – 5555Cytoplasmic By similarity
Transmembrane56 – 7924Helical; By similarity
Topological domain80 – 523444Extracellular By similarity
Transmembrane524 – 55532Helical; By similarity
Topological domain556 – 64994Cytoplasmic By similarity

Amino acid modifications

Glycosylation2091N-linked (GlcNAc...) Potential
Glycosylation2481N-linked (GlcNAc...) Potential
Glycosylation2711N-linked (GlcNAc...) Potential
Glycosylation2911N-linked (GlcNAc...) Potential
Glycosylation4971N-linked (GlcNAc...) Potential

Natural variations

Natural variant491G → C. Ref.16
Corresponds to variant rs5733 [ dbSNP | Ensembl ].
VAR_014893
Natural variant581G → R in a colorectal cancer sample; somatic mutation. Ref.17
VAR_036483
Natural variant1781R → W. Ref.2 Ref.15
VAR_015842
Natural variant1831G → S in a patient with bronchiectasis. Ref.16 Ref.18
Corresponds to variant rs5736 [ dbSNP | Ensembl ].
VAR_014894
Natural variant1971E → K in a patient with bronchiectasis. Ref.18
Corresponds to variant rs5738 [ dbSNP | Ensembl ].
VAR_034485
Natural variant5021A → P. Ref.2 Ref.3 Ref.5 Ref.15
VAR_015843
Natural variant6141A → S. Ref.2 Ref.15
VAR_015844

Experimental info

Sequence conflict3391F → S in CAA60633. Ref.1
Sequence conflict3501A → T in CAA60633. Ref.1
Sequence conflict3691Y → S in CAA60633. Ref.1
Sequence conflict3751D → G in CAA60633. Ref.1
Sequence conflict4581S → R in CAA60633. Ref.1
Sequence conflict461 – 4633EWT → DGH in AAC50758. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P51170 [UniParc].

Last modified May 30, 2006. Version 4.
Checksum: F67ED45F03A9BF3F

FASTA64974,270
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4 AND WWP2.
[10]"Proteolytic processing of the epithelial sodium channel gamma subunit has a dominant role in channel activation."
Carattino M.D., Hughey R.P., Kleyman T.R.
J. Biol. Chem. 283:25290-25295(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING.
[11]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BESC3.
[12]"Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9)."
Sharotri V., Collier D.M., Olson D.R., Zhou R., Snyder P.M.
J. Biol. Chem. 287:19266-19274(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PCSK9.
[13]"Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures."
Hobbs C.A., Blanchard M.G., Alijevic O., Tan C.D., Kellenberger S., Bencharit S., Cao R., Kesimer M., Walton W.G., Henderson A.G., Redinbo M.R., Stutts M.J., Tarran R.
Am. J. Physiol. 305:L990-L1001(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
[14]"ENaC modulators and renal disease."
Alvarez de la Rosa D., Navarro-Gonzalez J.F., Giraldez T.
Curr. Mol. Pharmacol. 6:35-43(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS TRP-178; PRO-502 AND SER-614.
[16]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-49 AND SER-183.
[17]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-58.
[18]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-183 AND LYS-197, INVOLVEMENT IN BESC3.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X87160 mRNA. Translation: CAA60633.1.
L36592 mRNA. Translation: AAA75460.1.
AF356502 expand/collapse EMBL AC list , 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.
PIRI38204.
I64847.
RefSeqNP_001030.2. NM_001039.3.
UniGeneHs.371727.

3D structure databases

ProteinModelPortalP51170.
SMRP51170. Positions 51-550.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112244. 12 interactions.
IntActP51170. 1 interaction.
MINTMINT-198604.

Chemistry

ChEMBLCHEMBL2107836.
DrugBankDB00594. Amiloride.
DB00384. Triamterene.

Protein family/group databases

TCDB1.A.6.1.1. the epithelial na(+) channel (enac) family.

PTM databases

PhosphoSiteP51170.

Polymorphism databases

DMDM108885072.

Proteomic databases

PaxDbP51170.
PRIDEP51170.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300061; ENSP00000300061; ENSG00000166828.
GeneID6340.
KEGGhsa:6340.
UCSCuc002dlm.1. human.

Organism-specific databases

CTD6340.
GeneCardsGC16P023101.
HGNCHGNC:10602. SCNN1G.
MIM177200. phenotype.
600761. gene.
613071. phenotype.
neXtProtNX_P51170.
Orphanet171876. Generalized pseudohypoaldosteronism type 1.
60033. Idiopathic bronchiectasis.
526. Liddle syndrome.
PharmGKBPA307.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG294559.
HOVERGENHBG058435.
InParanoidP51170.
KOK04827.
OMANWMYCYY.
OrthoDBEOG7T1R9N.
PhylomeDBP51170.
TreeFamTF330663.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP51170.
BgeeP51170.
GenevestigatorP51170.

Family and domain databases

InterProIPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERPTHR11690. PTHR11690. 1 hit.
PfamPF00858. ASC. 1 hit.
[Graphical view]
PRINTSPR01078. AMINACHANNEL.
TIGRFAMsTIGR00859. ENaC. 1 hit.
PROSITEPS01206. ASC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSCNN1G.
GenomeRNAi6340.
NextBio24620.
PROP51170.
SOURCESearch...

Entry information

Entry nameSCNNG_HUMAN
AccessionPrimary (citable) accession number: P51170
Secondary accession number(s): P78437 expand/collapse secondary AC list , 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: April 16, 2014
This is version 140 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM