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Q61180 (SCNNA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Amiloride-sensitive sodium channel subunit alpha
Alternative name(s):
Alpha-NaCH
Epithelial Na(+) channel subunit alpha
Short name=Alpha-ENaC
Nonvoltage-gated sodium channel 1 subunit alpha
SCNEA
Gene names
Name:Scnn1a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length699 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.

Enzyme regulation

Activated by WNK1, WNK2, WNK3 and WNK4. Ref.7

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.4 Ref.5 Ref.6

Subcellular location

Apical cell membrane; Multi-pass membrane protein By similarity. Cell projectioncilium By similarity. Note: In multi-ciliated cells, located on cilia. In non-ciliated epithelial cells, restricted to apical surfaces By similarity.

Tissue specificity

Expressed in kidney and lung (at protein level). Also expressed in distal colon and, at low levels, in liver. Ref.8

Post-translational modification

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 By similarity.

Sequence similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Sensory transduction
Sodium transport
Taste
Transport
   Cellular componentCell membrane
Cell projection
Membrane
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
   PTMGlycoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processmulticellular organismal water homeostasis

Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB

sodium ion transmembrane transport

Inferred from direct assay Ref.1PubMed 16941024. Source: GOC

sodium ion transport

Inferred from direct assay Ref.1. Source: MGI

   Cellular_componentapical plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ciliary membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cortical actin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from direct assay PubMed 21413931. Source: MGI

external side of plasma membrane

Inferred from direct assay PubMed 17715136. Source: MGI

integral component of membrane

Inferred from direct assay Ref.1. Source: MGI

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from direct assay PubMed 17715136PubMed 21413931. Source: MGI

motile cilium

Inferred from sequence or structural similarity. Source: UniProtKB

sodium channel complex

Inferred from genetic interaction PubMed 17715136. Source: MGI

   Molecular_functionWW domain binding

Inferred from physical interaction PubMed 10212229. Source: MGI

ligand-gated sodium channel activity

Inferred from direct assay Ref.1. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 699699Amiloride-sensitive sodium channel subunit alpha
PRO_0000181262

Regions

Topological domain1 – 111111Cytoplasmic By similarity
Transmembrane112 – 13524Helical; By similarity
Topological domain136 – 570435Extracellular By similarity
Transmembrane571 – 60131Helical; By similarity
Topological domain602 – 69897Cytoplasmic By similarity
Compositional bias68 – 714Poly-Glu
Compositional bias221 – 2266Poly-Pro

Amino acid modifications

Glycosylation1901N-linked (GlcNAc...) Potential
Glycosylation2591N-linked (GlcNAc...) Potential
Glycosylation3201N-linked (GlcNAc...) Potential
Glycosylation3391N-linked (GlcNAc...) Potential
Glycosylation4241N-linked (GlcNAc...) Potential
Glycosylation5381N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict4451H → R in AAA97412. Ref.3
Sequence conflict555 – 5573FKE → YKH in AAA97412. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q61180 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 5B083BE8769B017A

FASTA69978,893
        10         20         30         40         50         60 
MLDHTRAPEL NLDLDLDVSN SPKGSMKGNN FKEQDLCPPL PMQGLGKGDK REEQALGPEP 

        70         80         90        100        110        120 
SEPRQPTEEE EALIEFHRSY RELFQFFCNN TTIHGAIRLV CSKHNRMKTA FWAVLWLCTF 

       130        140        150        160        170        180 
GMMYWQFALL FEEYFSYPVS LNINLNSDKL VFPAVTVCTL NPYRYTEIKE DLEELDRITE 

       190        200        210        220        230        240 
QTLFDLYKYN SSYTRQAGGR RRSTRDLRGA LPHPLQRLRT PPPPNPARSA RSASSSVRDN 

       250        260        270        280        290        300 
NPQVDRKDWK IGFQLCNQNK SDCFYQTYSS GVDAVREWYR FHYINILSRL PDTSPALEEE 

       310        320        330        340        350        360 
ALGSFIFTCR FNQAPCNQAN YSQFHHPMYG NCYTFNNKNN SNLWMSSMPG VNNGLSLTLR 

       370        380        390        400        410        420 
TEQNDFIPLL STVTGARVMV HGQDEPAFMD DGGFNVRPGV ETSISMRKEA LDSLGGNYGD 

       430        440        450        460        470        480 
CTENGSDVPV KNLYPSKYTQ QVCIHSCFQE NMIKKCGCAY IFYPKPKGVE FCDYLKQSSW 

       490        500        510        520        530        540 
GYCYYKLQAA FSLDSLGCFS KCRKPCSVTN YKLSAGYSRW PSVKSQDWIF EMLSLQNNYT 

       550        560        570        580        590        600 
INNKRNGVAK LNIFFKELNY KTNSESPSVT MVSLLSNLGS QWSLWFGSSV LSVVEMAELI 

       610        620        630        640        650        660 
FDLLVITLIM LLHRFRSRYW SPGRGARGAR EVASTPASSF PSRFCPHPTS PPPSLPQQGT 

       670        680        690 
TPPLALTAPP PAYATLGPSA SPLDSAVPGS SACAPAMAL 

« Hide

References

[1]"Cloning and functional expression of the mouse epithelial sodium channel."
Ahn Y.J., Brooker D.R., Kosari F., Harte B.J., Li J., Mackler S.A., Kleyman T.R.
Am. J. Physiol. 277:F121-F129(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
Tissue: Kidney.
[2]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 432-437, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[3]"The alpha subunit of the epithelial sodium channel in the mouse: developmental regulation of its expression."
Dagenais A., Kothary R., Berthiaume Y.
Pediatr. Res. 42:327-334(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 445-558.
Strain: CD-1.
Tissue: Kidney.
[4]"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.
[5]"The role of individual Nedd4-2 (KIAA0439) WW domains in binding and regulating epithelial sodium channels."
Fotia A.B., Dinudom A., Shearwin K.E., Koch J.-P., Korbmacher C., Cook D.I., Kumar S.
FASEB J. 17:70-72(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4L.
[6]"Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2."
Fotia A.B., Ekberg J., Adams D.J., Cook D.I., Poronnik P., Kumar S.
J. Biol. Chem. 279:28930-28935(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4 AND NEDD4L.
[7]"Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members."
Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S., Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H.
J. Biol. Chem. 285:25161-25167(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[8]"Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways."
Enuka Y., Hanukoglu I., Edelheit O., Vaknine H., Hanukoglu A.
Histochem. Cell Biol. 137:339-353(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF112185 mRNA. Translation: AAD21244.1.
U52006 mRNA. Translation: AAA97412.1.
RefSeqNP_035454.2. NM_011324.2.
UniGeneMm.144114.

3D structure databases

ProteinModelPortalQ61180.
SMRQ61180. Positions 306-596.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203105. 3 interactions.
DIPDIP-40889N.
MINTMINT-90166.
STRING10090.ENSMUSP00000080164.

PTM databases

PhosphoSiteQ61180.

Proteomic databases

PRIDEQ61180.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID20276.
KEGGmmu:20276.

Organism-specific databases

CTD6337.
MGIMGI:101782. Scnn1a.

Phylogenomic databases

eggNOGNOG288544.
HOVERGENHBG058435.
InParanoidQ61180.
KOK04824.
OMASRQNNYT.
PhylomeDBQ61180.

Gene expression databases

ArrayExpressQ61180.
BgeeQ61180.
CleanExMM_SCNN1A.
GenevestigatorQ61180.

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

NextBio297963.
PMAP-CutDBQ61180.
PROQ61180.
SOURCESearch...

Entry information

Entry nameSCNNA_MOUSE
AccessionPrimary (citable) accession number: Q61180
Secondary accession number(s): Q9WU37
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 1, 2000
Last modified: July 9, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot