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Q61180

- SCNNA_MOUSE

UniProt

Q61180 - SCNNA_MOUSE

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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

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
Complete GO annotation...

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. extracellular vesicular exosome Source: Ensembl
  7. integral component of membrane Source: MGI
  8. integral component of plasma membrane Source: UniProtKB
  9. membrane Source: MGI
  10. motile cilium Source: UniProtKB
  11. sodium channel complex Source: MGI
Complete GO annotation...

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

BgeeiQ61180.
CleanExiMM_SCNN1A.
ExpressionAtlasiQ61180. baseline and differential.
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

        10         20         30         40         50
MLDHTRAPEL NLDLDLDVSN SPKGSMKGNN FKEQDLCPPL PMQGLGKGDK
60 70 80 90 100
REEQALGPEP SEPRQPTEEE EALIEFHRSY RELFQFFCNN TTIHGAIRLV
110 120 130 140 150
CSKHNRMKTA FWAVLWLCTF GMMYWQFALL FEEYFSYPVS LNINLNSDKL
160 170 180 190 200
VFPAVTVCTL NPYRYTEIKE DLEELDRITE QTLFDLYKYN SSYTRQAGGR
210 220 230 240 250
RRSTRDLRGA LPHPLQRLRT PPPPNPARSA RSASSSVRDN NPQVDRKDWK
260 270 280 290 300
IGFQLCNQNK SDCFYQTYSS GVDAVREWYR FHYINILSRL PDTSPALEEE
310 320 330 340 350
ALGSFIFTCR FNQAPCNQAN YSQFHHPMYG NCYTFNNKNN SNLWMSSMPG
360 370 380 390 400
VNNGLSLTLR TEQNDFIPLL STVTGARVMV HGQDEPAFMD DGGFNVRPGV
410 420 430 440 450
ETSISMRKEA LDSLGGNYGD CTENGSDVPV KNLYPSKYTQ QVCIHSCFQE
460 470 480 490 500
NMIKKCGCAY IFYPKPKGVE FCDYLKQSSW GYCYYKLQAA FSLDSLGCFS
510 520 530 540 550
KCRKPCSVTN YKLSAGYSRW PSVKSQDWIF EMLSLQNNYT INNKRNGVAK
560 570 580 590 600
LNIFFKELNY KTNSESPSVT MVSLLSNLGS QWSLWFGSSV LSVVEMAELI
610 620 630 640 650
FDLLVITLIM LLHRFRSRYW SPGRGARGAR EVASTPASSF PSRFCPHPTS
660 670 680 690
PPPSLPQQGT TPPLALTAPP PAYATLGPSA SPLDSAVPGS SACAPAMAL
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

Bgeei Q61180.
CleanExi MM_SCNN1A.
ExpressionAtlasi Q61180. baseline and differential.
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 29, 2014
This is version 117 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