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Q61180

- SCNNA_MOUSE

UniProt

Q61180 - SCNNA_MOUSE

Protein

Amiloride-sensitive sodium channel subunit alpha

Gene

Scnn1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 2 (01 Dec 2000)
      Previous versions | rss
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    Functioni

    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 regulationi

    Activated by WNK1, WNK2, WNK3 and WNK4.1 Publication

    GO - Molecular functioni

    1. ligand-gated sodium channel activity Source: MGI
    2. WW domain binding Source: MGI

    GO - Biological processi

    1. multicellular organismal water homeostasis Source: UniProtKB
    2. response to stimulus Source: UniProtKB-KW
    3. sensory perception of taste Source: UniProtKB-KW
    4. sodium ion homeostasis Source: UniProtKB
    5. sodium ion transmembrane transport Source: GOC
    6. sodium ion transport Source: MGI

    Keywords - Molecular functioni

    Ion channel, Sodium channel

    Keywords - Biological processi

    Ion transport, Sensory transduction, Sodium transport, Taste, Transport

    Keywords - Ligandi

    Sodium

    Enzyme and pathway databases

    ReactomeiREACT_196640. Stimuli-sensing channels.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:Scnn1a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:101782. Scnn1a.

    Subcellular locationi

    Apical cell membrane By similarity; 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.By similarity

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB
    2. ciliary membrane Source: UniProtKB
    3. cortical actin cytoskeleton Source: Ensembl
    4. cytosol Source: MGI
    5. external side of plasma membrane Source: MGI
    6. integral component of membrane Source: MGI
    7. integral component of plasma membrane Source: UniProtKB
    8. membrane Source: MGI
    9. motile cilium Source: UniProtKB
    10. sodium channel complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 699699Amiloride-sensitive sodium channel subunit alphaPRO_0000181262Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi190 – 1901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi259 – 2591N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi320 – 3201N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi339 – 3391N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi424 – 4241N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi538 – 5381N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    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.By similarity

    Keywords - PTMi

    Glycoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ61180.

    PTM databases

    PhosphoSiteiQ61180.

    Miscellaneous databases

    PMAP-CutDBQ61180.

    Expressioni

    Tissue specificityi

    Expressed in kidney and lung (at protein level). Also expressed in distal colon and, at low levels, in liver.1 Publication

    Gene expression databases

    ArrayExpressiQ61180.
    BgeeiQ61180.
    CleanExiMM_SCNN1A.
    GenevestigatoriQ61180.

    Interactioni

    Subunit structurei

    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.By similarity

    Protein-protein interaction databases

    BioGridi203105. 3 interactions.
    DIPiDIP-40889N.
    MINTiMINT-90166.
    STRINGi10090.ENSMUSP00000080164.

    Structurei

    3D structure databases

    ProteinModelPortaliQ61180.
    SMRiQ61180. Positions 306-596.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 111111CytoplasmicBy similarityAdd
    BLAST
    Topological domaini136 – 570435ExtracellularBy similarityAdd
    BLAST
    Topological domaini602 – 69897CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei112 – 13524HelicalBy similarityAdd
    BLAST
    Transmembranei571 – 60131HelicalBy similarityAdd
    BLAST

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi68 – 714Poly-Glu
    Compositional biasi221 – 2266Poly-Pro

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG288544.
    HOVERGENiHBG058435.
    InParanoidiQ61180.
    KOiK04824.
    OMAiSRQNNYT.
    PhylomeDBiQ61180.

    Family and domain databases

    InterProiIPR004724. EnaC.
    IPR001873. Na+channel_ASC.
    IPR020903. Na+channel_ASC_CS.
    [Graphical view]
    PANTHERiPTHR11690. PTHR11690. 1 hit.
    PfamiPF00858. ASC. 1 hit.
    [Graphical view]
    PRINTSiPR01078. AMINACHANNEL.
    TIGRFAMsiTIGR00859. ENaC. 1 hit.
    PROSITEiPS01206. ASC. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q61180-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLDHTRAPEL NLDLDLDVSN SPKGSMKGNN FKEQDLCPPL PMQGLGKGDK    50
    REEQALGPEP SEPRQPTEEE EALIEFHRSY RELFQFFCNN TTIHGAIRLV 100
    CSKHNRMKTA FWAVLWLCTF GMMYWQFALL FEEYFSYPVS LNINLNSDKL 150
    VFPAVTVCTL NPYRYTEIKE DLEELDRITE QTLFDLYKYN SSYTRQAGGR 200
    RRSTRDLRGA LPHPLQRLRT PPPPNPARSA RSASSSVRDN NPQVDRKDWK 250
    IGFQLCNQNK SDCFYQTYSS GVDAVREWYR FHYINILSRL PDTSPALEEE 300
    ALGSFIFTCR FNQAPCNQAN YSQFHHPMYG NCYTFNNKNN SNLWMSSMPG 350
    VNNGLSLTLR TEQNDFIPLL STVTGARVMV HGQDEPAFMD DGGFNVRPGV 400
    ETSISMRKEA LDSLGGNYGD CTENGSDVPV KNLYPSKYTQ QVCIHSCFQE 450
    NMIKKCGCAY IFYPKPKGVE FCDYLKQSSW GYCYYKLQAA FSLDSLGCFS 500
    KCRKPCSVTN YKLSAGYSRW PSVKSQDWIF EMLSLQNNYT INNKRNGVAK 550
    LNIFFKELNY KTNSESPSVT MVSLLSNLGS QWSLWFGSSV LSVVEMAELI 600
    FDLLVITLIM LLHRFRSRYW SPGRGARGAR EVASTPASSF PSRFCPHPTS 650
    PPPSLPQQGT TPPLALTAPP PAYATLGPSA SPLDSAVPGS SACAPAMAL 699
    Length:699
    Mass (Da):78,893
    Last modified:December 1, 2000 - v2
    Checksum:i5B083BE8769B017A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti445 – 4451H → R in AAA97412. (PubMed:9284273)Curated
    Sequence conflicti555 – 5573FKE → YKH in AAA97412. (PubMed:9284273)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF112185 mRNA. Translation: AAD21244.1.
    U52006 mRNA. Translation: AAA97412.1.
    RefSeqiNP_035454.2. NM_011324.2.
    UniGeneiMm.144114.

    Genome annotation databases

    GeneIDi20276.
    KEGGimmu:20276.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF112185 mRNA. Translation: AAD21244.1 .
    U52006 mRNA. Translation: AAA97412.1 .
    RefSeqi NP_035454.2. NM_011324.2.
    UniGenei Mm.144114.

    3D structure databases

    ProteinModelPortali Q61180.
    SMRi Q61180. Positions 306-596.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 203105. 3 interactions.
    DIPi DIP-40889N.
    MINTi MINT-90166.
    STRINGi 10090.ENSMUSP00000080164.

    PTM databases

    PhosphoSitei Q61180.

    Proteomic databases

    PRIDEi Q61180.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 20276.
    KEGGi mmu:20276.

    Organism-specific databases

    CTDi 6337.
    MGIi MGI:101782. Scnn1a.

    Phylogenomic databases

    eggNOGi NOG288544.
    HOVERGENi HBG058435.
    InParanoidi Q61180.
    KOi K04824.
    OMAi SRQNNYT.
    PhylomeDBi Q61180.

    Enzyme and pathway databases

    Reactomei REACT_196640. Stimuli-sensing channels.

    Miscellaneous databases

    NextBioi 297963.
    PMAP-CutDB Q61180.
    PROi Q61180.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q61180.
    Bgeei Q61180.
    CleanExi MM_SCNN1A.
    Genevestigatori Q61180.

    Family and domain databases

    InterProi IPR004724. EnaC.
    IPR001873. Na+channel_ASC.
    IPR020903. Na+channel_ASC_CS.
    [Graphical view ]
    PANTHERi PTHR11690. PTHR11690. 1 hit.
    Pfami PF00858. ASC. 1 hit.
    [Graphical view ]
    PRINTSi PR01078. AMINACHANNEL.
    TIGRFAMsi TIGR00859. ENaC. 1 hit.
    PROSITEi PS01206. ASC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiSCNNA_MOUSE
    AccessioniPrimary (citable) accession number: Q61180
    Secondary accession number(s): Q9WU37
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: December 1, 2000
    Last modified: October 1, 2014
    This is version 116 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3