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P37088

- SCNNA_HUMAN

UniProt

P37088 - SCNNA_HUMAN

Protein

Amiloride-sensitive sodium channel subunit alpha

Gene

SCNN1A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 152 (01 Oct 2014)
      Sequence version 1 (01 Oct 1994)
      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.1 Publication

    Enzyme regulationi

    Activated by WNK1, WNK2, WNK3 and WNK4.By similarity

    GO - Molecular functioni

    1. ligand-gated sodium channel activity Source: Ensembl
    2. protein binding Source: UniProtKB
    3. WW domain binding Source: BHF-UCL

    GO - Biological processi

    1. excretion Source: ProtInc
    2. ion transmembrane transport Source: Reactome
    3. multicellular organismal water homeostasis Source: UniProtKB
    4. response to stimulus Source: UniProtKB-KW
    5. sensory perception of taste Source: UniProtKB-KW
    6. sodium ion homeostasis Source: UniProtKB
    7. sodium ion transmembrane transport Source: UniProtKB
    8. sodium ion transport Source: ProtInc
    9. transmembrane transport Source: Reactome

    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_160189. Stimuli-sensing channels.

    Protein family/group databases

    TCDBi1.A.6.1.1. the epithelial na(+) channel (enac) family.

    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
    Short name:
    ENaCA
    Nonvoltage-gated sodium channel 1 subunit alpha
    SCNEA
    Gene namesi
    Name:SCNN1A
    Synonyms:SCNN1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:10599. SCNN1A.

    Subcellular locationi

    Apical cell membrane; Multi-pass membrane protein. Cell projectioncilium
    Note: In the oviduct and bronchus, located on cilia in multi-ciliated cells. In endometrial non-ciliated epithelial cells, restricted to apical surfaces.

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Pseudohypoaldosteronism 1, autosomal recessive (PHA1B) [MIM:264350]: A rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1B is a severe form involving multiple organ systems, and characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878).1 Publication
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti327 – 3271G → C in PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents. 2 Publications
    VAR_026518
    Natural varianti562 – 5621S → L in PHA1B. 1 Publication
    VAR_015834
    Bronchiectasis with or without elevated sweat chloride 2 (BESC2) [MIM:613021]: 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti61 – 611F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. 1 Publication
    Corresponds to variant rs61758859 [ dbSNP | Ensembl ].
    VAR_060793
    Natural varianti114 – 1141V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. 1 Publication
    Corresponds to variant rs61759861 [ dbSNP | Ensembl ].
    VAR_060794
    Natural varianti493 – 4931W → R Functional polymorphism resulting in a 4-fold increase of amiloride-sensitive sodium currents; found in BESC2 patients at higher frequency than in controls; associated with an incresed risk for ischemic cerebrovascular events. 2 Publications
    Corresponds to variant rs5742912 [ dbSNP | Ensembl ].
    VAR_015833

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi264350. phenotype.
    613021. phenotype.
    Orphaneti171876. Generalized pseudohypoaldosteronism type 1.
    60033. Idiopathic bronchiectasis.
    PharmGKBiPA305.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 669669Amiloride-sensitive sodium channel subunit alphaPRO_0000181261Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi232 – 2321N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi293 – 2931N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi312 – 3121N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi397 – 3971N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi511 – 5111N-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.1 Publication

    Keywords - PTMi

    Glycoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP37088.
    PRIDEiP37088.

    PTM databases

    PhosphoSiteiP37088.

    Expressioni

    Tissue specificityi

    Expressed in the female reproductive tract, from the fimbrial end of the fallopian tube to the endometrium (at protein level). Expressed in kidney (at protein level). In the respiratory tract, expressed in the bronchial epithelium (at protein level). Highly expressed in lung. Detected at intermediate levels in pancreas and liver, and at low levels in heart and placenta. Isoform 1 and isoform 2 predominate in all tissues. Expression of isoform 3, isoform 4 and isoform 5 is very low or not detectable, except in lung and heart.2 Publications

    Inductioni

    By aldosterone.1 Publication

    Gene expression databases

    ArrayExpressiP37088.
    BgeeiP37088.
    CleanExiHS_SCNN1A.
    GenevestigatoriP37088.

    Organism-specific databases

    HPAiHPA012743.
    HPA012939.

    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).6 Publications

    Protein-protein interaction databases

    BioGridi112241. 20 interactions.
    MINTiMINT-198663.
    STRINGi9606.ENSP00000228916.

    Structurei

    Secondary structure

    1
    669
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi644 – 6474

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2M3ONMR-P638-648[»]
    ProteinModelPortaliP37088.
    SMRiP37088. Positions 279-566.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8686CytoplasmicBy similarityAdd
    BLAST
    Topological domaini111 – 543433ExtracellularBy similarityAdd
    BLAST
    Topological domaini575 – 66995CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei87 – 11024HelicalBy similarityAdd
    BLAST
    Transmembranei544 – 57431HelicalBy similarityAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG288544.
    HOGENOMiHOG000236286.
    HOVERGENiHBG058435.
    InParanoidiP37088.
    KOiK04824.
    OMAiSRQNNYT.
    OrthoDBiEOG7T1R9N.
    PhylomeDBiP37088.
    TreeFamiTF330663.

    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]

    Sequences (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P37088-1) [UniParc]FASTAAdd to Basket

    Also known as: Alpha ENAC1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE    50
    FHRSYRELFE FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW 100
    QFGLLFGEYF SYPVSLNINL NSDKLVFPAV TICTLNPYRY PEIKEELEEL 150
    DRITEQTLFD LYKYSSFTTL VAGSRSRRDL RGTLPHPLQR LRVPPPPHGA 200
    RRARSVASSL RDNNPQVDWK DWKIGFQLCN QNKSDCFYQT YSSGVDAVRE 250
    WYRFHYINIL SRLPETLPSL EEDTLGNFIF ACRFNQVSCN QANYSHFHHP 300
    MYGNCYTFND KNNSNLWMSS MPGINNGLSL MLRAEQNDFI PLLSTVTGAR 350
    VMVHGQDEPA FMDDGGFNLR PGVETSISMR KETLDRLGGD YGDCTKNGSD 400
    VPVENLYPSK YTQQVCIHSC FQESMIKECG CAYIFYPRPQ NVEYCDYRKH 450
    SSWGYCYYKL QVDFSSDHLG CFTKCRKPCS VTSYQLSAGY SRWPSVTSQE 500
    WVFQMLSRQN NYTVNNKRNG VAKVNIFFKE LNYKTNSESP SVTMVTLLSN 550
    LGSQWSLWFG SSVLSVVEMA ELVFDLLVIM FLMLLRRFRS RYWSPGRGGR 600
    GAQEVASTLA SSPPSHFCPH PMSLSLSQPG PAPSPALTAP PPAYATLGPR 650
    PSPGGSAGAS SSTCPLGGP 669
    Length:669
    Mass (Da):75,704
    Last modified:October 1, 1994 - v1
    Checksum:i2CCF342E7DF32E72
    GO
    Isoform 2 (identifier: P37088-2) [UniParc]FASTAAdd to Basket

    Also known as: Alpha ENAC2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MGMARGSLTRVPGVMGEGTQGPELSLDPDPCSPQSTPGLMKGNKLEEQDPRPLQPIPGLM

    Show »
    Length:728
    Mass (Da):81,856
    Checksum:i206613374DFB1800
    GO
    Isoform 3 (identifier: P37088-3) [UniParc]FASTAAdd to Basket

    Also known as: Alpha ENACx

    The sequence of this isoform differs from the canonical sequence as follows:
         229-245: CNQNKSDCFYQTYSSGV → ELLSLPPPDVWKLLYFG
         246-669: Missing.

    Note: Does not give rise to amiloride-sensitive ion current. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Show »
    Length:245
    Mass (Da):28,328
    Checksum:iFFDC0622FFA37329
    GO
    Isoform 4 (identifier: P37088-4) [UniParc]FASTAAdd to Basket

    Also known as: Alpha ENAC-19

    The sequence of this isoform differs from the canonical sequence as follows:
         327-345: Missing.

    Note: Amiloride-sensitive ion current is nearly abolished.

    Show »
    Length:650
    Mass (Da):73,603
    Checksum:i5866D42CCAF6F8B4
    GO
    Isoform 5 (identifier: P37088-5) [UniParc]FASTAAdd to Basket

    Also known as: Alpha ENAC+22

    The sequence of this isoform differs from the canonical sequence as follows:
         454-454: G → GQVRSLTPVIPALWEAEAGGSRG

    Note: Does not give rise to amiloride-sensitive ion current.

    Show »
    Length:691
    Mass (Da):77,980
    Checksum:i07B981FBE74AE30B
    GO
    Isoform 6 (identifier: P37088-6) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MSSIKGNKLEEQDPRPLQPIPGLM

    Note: No experimental confirmation available.

    Show »
    Length:692
    Mass (Da):78,234
    Checksum:i3AD7710E69D1BE54
    GO

    Sequence cautioni

    The sequence AAH06526.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti61 – 611F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. 1 Publication
    Corresponds to variant rs61758859 [ dbSNP | Ensembl ].
    VAR_060793
    Natural varianti114 – 1141V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. 1 Publication
    Corresponds to variant rs61759861 [ dbSNP | Ensembl ].
    VAR_060794
    Natural varianti181 – 1811R → W Functional polymorphism; significant increase of amiloride-sensitive sodium currents. 2 Publications
    Corresponds to variant rs55797039 [ dbSNP | Ensembl ].
    VAR_060795
    Natural varianti327 – 3271G → C in PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents. 2 Publications
    VAR_026518
    Natural varianti334 – 3341A → T Functional polymorphism; significant decrease of amiloride-sensitive sodium currents. 2 Publications
    Corresponds to variant rs11542844 [ dbSNP | Ensembl ].
    VAR_060796
    Natural varianti402 – 4021P → H.
    Corresponds to variant rs13306616 [ dbSNP | Ensembl ].
    VAR_052035
    Natural varianti493 – 4931W → R Functional polymorphism resulting in a 4-fold increase of amiloride-sensitive sodium currents; found in BESC2 patients at higher frequency than in controls; associated with an incresed risk for ischemic cerebrovascular events. 2 Publications
    Corresponds to variant rs5742912 [ dbSNP | Ensembl ].
    VAR_015833
    Natural varianti562 – 5621S → L in PHA1B. 1 Publication
    VAR_015834
    Natural varianti573 – 5731V → I.
    Corresponds to variant rs59142484 [ dbSNP | Ensembl ].
    VAR_060797
    Natural varianti618 – 6181C → F.1 Publication
    Corresponds to variant rs3741913 [ dbSNP | Ensembl ].
    VAR_022142
    Natural varianti663 – 6631T → A.7 Publications
    Corresponds to variant rs2228576 [ dbSNP | Ensembl ].
    VAR_015835

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MGMARGSLTRVPGVMGEGTQ GPELSLDPDPCSPQSTPGLM KGNKLEEQDPRPLQPIPGLM in isoform 2. CuratedVSP_007719
    Alternative sequencei1 – 11M → MSSIKGNKLEEQDPRPLQPI PGLM in isoform 6. 1 PublicationVSP_043667
    Alternative sequencei229 – 24517CNQNK…YSSGV → ELLSLPPPDVWKLLYFG in isoform 3. CuratedVSP_007720Add
    BLAST
    Alternative sequencei246 – 669424Missing in isoform 3. CuratedVSP_007721Add
    BLAST
    Alternative sequencei327 – 34519Missing in isoform 4. CuratedVSP_007722Add
    BLAST
    Alternative sequencei454 – 4541G → GQVRSLTPVIPALWEAEAGG SRG in isoform 5. CuratedVSP_007723

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X76180 mRNA. Translation: CAA53773.1.
    L29007 Genomic DNA. Translation: AAA21813.1.
    Z92978
    , Z92979, Z92980, Z92981 Genomic DNA. Translation: CAB07505.1.
    AF060913
    , AF060910, AF060911, AF060912 Genomic DNA. Translation: AAD28355.1.
    DQ402522 mRNA. Translation: ABD72218.1.
    AK304379 mRNA. Translation: BAG65217.1.
    FJ515830 Genomic DNA. Translation: ACS13721.1.
    AC005840 Genomic DNA. No translation available.
    AC006057 Genomic DNA. No translation available.
    CH471116 Genomic DNA. Translation: EAW88804.1.
    BC006526 mRNA. Translation: AAH06526.2. Different initiation.
    BC062613 mRNA. Translation: AAH62613.1.
    U81961 Genomic DNA. Translation: AAC31773.1.
    U81961 Genomic DNA. Translation: AAC31774.1.
    CCDSiCCDS53738.1. [P37088-2]
    CCDS53739.1. [P37088-6]
    CCDS8543.1. [P37088-1]
    PIRiA49585.
    RefSeqiNP_001029.1. NM_001038.5. [P37088-1]
    NP_001153047.1. NM_001159575.1. [P37088-6]
    NP_001153048.1. NM_001159576.1. [P37088-2]
    UniGeneiHs.591047.

    Genome annotation databases

    EnsembliENST00000228916; ENSP00000228916; ENSG00000111319. [P37088-1]
    ENST00000360168; ENSP00000353292; ENSG00000111319. [P37088-2]
    ENST00000543768; ENSP00000438739; ENSG00000111319. [P37088-6]
    GeneIDi6337.
    KEGGihsa:6337.
    UCSCiuc001qnv.3. human. [P37088-1]
    uc001qnw.3. human. [P37088-2]
    uc010sfb.2. human. [P37088-6]

    Polymorphism databases

    DMDMi585966.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X76180 mRNA. Translation: CAA53773.1 .
    L29007 Genomic DNA. Translation: AAA21813.1 .
    Z92978
    , Z92979 , Z92980 , Z92981 Genomic DNA. Translation: CAB07505.1 .
    AF060913
    , AF060910 , AF060911 , AF060912 Genomic DNA. Translation: AAD28355.1 .
    DQ402522 mRNA. Translation: ABD72218.1 .
    AK304379 mRNA. Translation: BAG65217.1 .
    FJ515830 Genomic DNA. Translation: ACS13721.1 .
    AC005840 Genomic DNA. No translation available.
    AC006057 Genomic DNA. No translation available.
    CH471116 Genomic DNA. Translation: EAW88804.1 .
    BC006526 mRNA. Translation: AAH06526.2 . Different initiation.
    BC062613 mRNA. Translation: AAH62613.1 .
    U81961 Genomic DNA. Translation: AAC31773.1 .
    U81961 Genomic DNA. Translation: AAC31774.1 .
    CCDSi CCDS53738.1. [P37088-2 ]
    CCDS53739.1. [P37088-6 ]
    CCDS8543.1. [P37088-1 ]
    PIRi A49585.
    RefSeqi NP_001029.1. NM_001038.5. [P37088-1 ]
    NP_001153047.1. NM_001159575.1. [P37088-6 ]
    NP_001153048.1. NM_001159576.1. [P37088-2 ]
    UniGenei Hs.591047.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2M3O NMR - P 638-648 [» ]
    ProteinModelPortali P37088.
    SMRi P37088. Positions 279-566.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112241. 20 interactions.
    MINTi MINT-198663.
    STRINGi 9606.ENSP00000228916.

    Chemistry

    BindingDBi P37088.
    ChEMBLi CHEMBL1791.
    DrugBanki DB00594. Amiloride.
    DB00384. Triamterene.

    Protein family/group databases

    TCDBi 1.A.6.1.1. the epithelial na(+) channel (enac) family.

    PTM databases

    PhosphoSitei P37088.

    Polymorphism databases

    DMDMi 585966.

    Proteomic databases

    PaxDbi P37088.
    PRIDEi P37088.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000228916 ; ENSP00000228916 ; ENSG00000111319 . [P37088-1 ]
    ENST00000360168 ; ENSP00000353292 ; ENSG00000111319 . [P37088-2 ]
    ENST00000543768 ; ENSP00000438739 ; ENSG00000111319 . [P37088-6 ]
    GeneIDi 6337.
    KEGGi hsa:6337.
    UCSCi uc001qnv.3. human. [P37088-1 ]
    uc001qnw.3. human. [P37088-2 ]
    uc010sfb.2. human. [P37088-6 ]

    Organism-specific databases

    CTDi 6337.
    GeneCardsi GC12M006456.
    HGNCi HGNC:10599. SCNN1A.
    HPAi HPA012743.
    HPA012939.
    MIMi 264350. phenotype.
    600228. gene.
    613021. phenotype.
    neXtProti NX_P37088.
    Orphaneti 171876. Generalized pseudohypoaldosteronism type 1.
    60033. Idiopathic bronchiectasis.
    PharmGKBi PA305.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG288544.
    HOGENOMi HOG000236286.
    HOVERGENi HBG058435.
    InParanoidi P37088.
    KOi K04824.
    OMAi SRQNNYT.
    OrthoDBi EOG7T1R9N.
    PhylomeDBi P37088.
    TreeFami TF330663.

    Enzyme and pathway databases

    Reactomei REACT_160189. Stimuli-sensing channels.

    Miscellaneous databases

    ChiTaRSi SCNN1A. human.
    GeneWikii SCNN1A.
    GenomeRNAii 6337.
    NextBioi 24608.
    PROi P37088.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P37088.
    Bgeei P37088.
    CleanExi HS_SCNN1A.
    Genevestigatori P37088.

    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. "The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning."
      Voilley N., Lingueglia E., Champigny G., Mattei M.-G., Waldmann R., Lazdunski M., Barbry P.
      Proc. Natl. Acad. Sci. U.S.A. 91:247-251(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Lung.
    2. "Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channel."
      McDonald F.J., Snyder P.M., McCray P.B. Jr., Welsh M.J.
      Am. J. Physiol. 266:L728-L734(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Kidney.
    3. "Structural organisation of the gene encoding the alpha-subunit of the human amiloride-sensitive epithelial sodium channel."
      Ludwig M., Bolkenius U., Wickert L., Marynen P., Bidlingmaier F.
      Hum. Genet. 102:576-581(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Hormonal regulation and genomic organization of the human amiloride-sensitive epithelial sodium channel alpha subunit gene."
      Chow Y.H., Wang Y., Plumb J., O'Brodovich H., Hu J.
      Pediatr. Res. 46:208-214(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "Upregulated expression of ENaC in human CF nasal epithelium."
      Bangel N., Dahlhoff C., Sobczak K., Weber W.M., Kusche-Vihrog K.
      J. Cyst. Fibros. 7:197-205(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-663.
      Tissue: Nasal epithelium.
    6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
      Tissue: Trachea.
    7. NHLBI resequencing and genotyping service (RS&G)
      Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    8. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    10. "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] (ISOFORM 1), VARIANT ALA-663.
      Tissue: Colon and Lung.
    11. "5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins."
      Thomas C.P., Auerbach S.D., Stokes J.B., Volk K.A.
      Am. J. Physiol. 274:C1312-C1323(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
      Tissue: Kidney.
    12. "The alpha-subunit of the epithelial sodium channel is an aldosterone-induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5'-flanking region of the gene."
      Mick V.E., Itani O.A., Loftus R.W., Husted R.F., Schmidt T.J., Thomas C.P.
      Mol. Endocrinol. 15:575-588(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50 (ISOFORMS 1 AND 2), INDUCTION.
      Tissue: Placenta.
    13. "Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects."
      Hanukoglu A.
      J. Clin. Endocrinol. Metab. 73:936-944(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEFINITION OF DIFFERENT FORMS OF PSEUDOHYPOALDOSTERONISM TYPE 1.
    14. "Cloning and functional studies of splice variants of the alpha-subunit of the amiloride-sensitive Na+ channel."
      Tucker J.K., Tamba K., Lee Y.-J., Shen L.-L., Warnock D.G., Oh Y.
      Am. J. Physiol. 274:C1081-C1089(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING (ISOFORMS 1; 3; 4 AND 5), TISSUE SPECIFICITY.
    15. "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.
    16. "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.
    17. "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.
    18. "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.
    19. "Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes."
      Hanukoglu A., Edelheit O., Shriki Y., Gizewska M., Dascal N., Hanukoglu I.
      J. Steroid Biochem. Mol. Biol. 111:268-274(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: GENOTYPE-PHENOTYPE RELATIONSHIPS IN PHA1B, LONG-TERM EFFECTS OF MUTATIONS ON PHA1B, VARIANT PHA1B CYS-327, CHARACTERIZATION OF VARIANT PHA1B CYS-327.
    20. "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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    21. "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.
    22. "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: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
    23. "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.
    24. "Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension."
      Ambrosius W.T., Bloem L.J., Zhou L., Rebhun J.F., Snyder P.M., Wagner M.A., Guo C., Pratt J.H.
      Hypertension 34:631-637(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS THR-334; PHE-618 AND ALA-663.
    25. "Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel."
      Snyder P.M., Olson D.R., Thomas B.C.
      J. Biol. Chem. 277:5-8(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NEDD4 AND NEDD4L.
    26. "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: VARIANT ALA-663.
    27. "Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel."
      Schaedel C., Marthinsen L., Kristoffersson A.-C., Kornfalt R., Nilsson K.O., Orlenius B., Holmberg L.
      J. Pediatr. 135:739-745(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PHA1B LEU-562, VARIANT ARG-493.
    28. "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: VARIANT ALA-663.
    29. "Impact of alphaENaC polymorphisms on the risk of ischemic cerebrovascular events: a multicenter case-control study."
      Hsieh K., Lalouschek W., Schillinger M., Endler G., Reisinger M., Janisiw M., Lang W., Cheng S., Wagner O., Mannhalter C.
      Clin. Chem. 51:952-956(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ALA-663, ASSOCIATION OF VARIANT ARG-493 WITH RISK FOR ISCHEMIC CEREBROVASCULAR EVENTS.
    30. "Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism."
      Edelheit O., Hanukoglu I., Gizewska M., Kandemir N., Tenenbaum-Rakover Y., Yurdakoek M., Zajaczek S., Hanukoglu A.
      Clin. Endocrinol. (Oxf.) 62:547-553(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PHA1B CYS-327.
    31. "Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome."
      Sheridan M.B., Fong P., Groman J.D., Conrad C., Flume P., Diaz R., Harris C., Knowles M., Cutting G.R.
      Hum. Mol. Genet. 14:3493-3498(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TRP-181.
    32. Cited for: VARIANTS BESC2 LEU-61 AND ILE-114, VARIANTS TRP-181; THR-334; ARG-493 AND ALA-663, CHARACTERIZATION OF VARIANTS BESC2 LEU-61 AND ILE-114, CHARACTERIZATION OF VARIANTS TRP-181; THR-334 AND ARG-493.

    Entry informationi

    Entry nameiSCNNA_HUMAN
    AccessioniPrimary (citable) accession number: P37088
    Secondary accession number(s): A5X2U9
    , B4E2Q5, C5HTZ0, O43271, Q6GSQ6, Q9UM64
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1994
    Last sequence update: October 1, 1994
    Last modified: October 1, 2014
    This is version 152 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3