LOCUS       NP_001029                669 aa            linear   PRI 28-APR-2025
DEFINITION  epithelial sodium channel subunit alpha isoform 1 [Homo sapiens].
ACCESSION   NP_001029
VERSION     NP_001029.1
DBSOURCE    REFSEQ: accession NM_001038.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 669)
  AUTHORS   Di,X., Hao,Y., Duan,Z., Ma,Y., Cao,Y., Tan,Z., Song,C. and Lin,X.
  TITLE     Activation of SGK1/ENaC Signaling Pathway Improves the Level of
            Decidualization in Unexplained Recurrent Spontaneous Abortion
  JOURNAL   Reprod Sci 30 (11), 3273-3284 (2023)
   PUBMED   37280474
  REMARK    GeneRIF: Activation of SGK1/ENaC Signaling Pathway Improves the
            Level of Decidualization in Unexplained Recurrent Spontaneous
            Abortion.
REFERENCE   2  (residues 1 to 669)
  AUTHORS   Sun,H., Zhou,Y., Jiang,S., Zhao,D., Li,H., Lu,Y., Ma,B. and Zhou,B.
  TITLE     Association between low-sodium salt intervention and long-term
            blood pressure changes is modified by ENaC genetic variation: a
            gene-diet interaction analysis in a randomized controlled trial
  JOURNAL   Food Funct 14 (21), 9782-9791 (2023)
   PUBMED   37843257
  REMARK    GeneRIF: Association between low-sodium salt intervention and
            long-term blood pressure changes is modified by ENaC genetic
            variation: a gene-diet interaction analysis in a randomized
            controlled trial.
            Erratum:[Food Funct. 2024 Jan 22;15(2):1050. doi:
            10.1039/d3fo90103c. PMID: 38126716]
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 669)
  AUTHORS   Efthymiadou,A., Gautschi,I., van Bemmelen,M.X., Sertedaki,A.,
            Giannakopoulos,A., Chrousos,G., Schild,L. and Chrysis,D.
  TITLE     A mild and transient form of autosomal recessive
            pseudohypoaldosteronism type 1 caused by a novel mutation in the
            SCNN1A gene
  JOURNAL   Am J Physiol Endocrinol Metab 325 (1), E1-E9 (2023)
   PUBMED   37134141
  REMARK    GeneRIF: A mild and transient form of autosomal recessive
            pseudohypoaldosteronism type 1 caused by a novel mutation in the
            SCNN1A gene.
REFERENCE   4  (residues 1 to 669)
  AUTHORS   Blobner,B.M., Kirabo,A., Kashlan,O.B., Sheng,S., Arnett,D.K.,
            Becker,L.C., Boerwinkle,E., Carlson,J.C., Gao,Y., Gibbs,R.A.,
            He,J., Irvin,M.R., Kardia,S.L.R., Kelly,T.N., Kooperberg,C.,
            McGarvey,S.T., Menon,V.K., Montasser,M.E., Naseri,T., Redline,S.,
            Reiner,A.P., Reupena,M.S., Smith,J.A., Sun,X., Vaidya,D.,
            Viaud-Martinez,K.A., Weeks,D.E., Yanek,L.R., Zhu,X., Minster,R.L.
            and Kleyman,T.R.
  CONSRTM   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium*
  TITLE     Rare Variants in Genes Encoding Subunits of the Epithelial Na+
            Channel Are Associated With Blood Pressure and Kidney Function
  JOURNAL   Hypertension 79 (11), 2573-2582 (2022)
   PUBMED   36193739
  REMARK    GeneRIF: Rare Variants in Genes Encoding Subunits of the Epithelial
            Na[+] Channel Are Associated With Blood Pressure and Kidney
            Function.
REFERENCE   5  (residues 1 to 669)
  AUTHORS   Gao,F., Wang,D., Liu,X., Wu,Y.H., Wang,H.T. and Sun,S.L.
  TITLE     Sodium channel 1 subunit alpha SCNN1A exerts oncogenic function in
            pancreatic cancer via accelerating cellular growth and metastasis
  JOURNAL   Arch Biochem Biophys 727, 109323 (2022)
   PUBMED   35714697
  REMARK    GeneRIF: Sodium channel 1 subunit alpha SCNN1A exerts oncogenic
            function in pancreatic cancer via accelerating cellular growth and
            metastasis.
REFERENCE   6  (residues 1 to 669)
  AUTHORS   Azad,A.K., Rauh,R., Vermeulen,F., Jaspers,M., Korbmacher,J.,
            Boissier,B., Bassinet,L., Fichou,Y., des Georges,M., Stanke,F., De
            Boeck,K., Dupont,L., Balascakova,M., Hjelte,L., Lebecque,P.,
            Radojkovic,D., Castellani,C., Schwartz,M., Stuhrmann,M.,
            Schwarz,M., Skalicka,V., de Monestrol,I., Girodon,E., Ferec,C.,
            Claustres,M., Tummler,B., Cassiman,J.J., Korbmacher,C. and
            Cuppens,H.
  TITLE     Mutations in the amiloride-sensitive epithelial sodium channel in
            patients with cystic fibrosis-like disease
  JOURNAL   Hum Mutat 30 (7), 1093-1103 (2009)
   PUBMED   19462466
  REMARK    GeneRIF: a more than three-fold significant increase in incidence
            of several rare ENaC polymorphisms was found in the patient group
            (30% vs. 9% in controls), indicating an involvement of ENaC in some
            patients by a polygenetic mechanism.
REFERENCE   7  (residues 1 to 669)
  AUTHORS   Chang,S.S., Grunder,S., Hanukoglu,A., Rosler,A., Mathew,P.M.,
            Hanukoglu,I., Schild,L., Lu,Y., Shimkets,R.A., Nelson-Williams,C.,
            Rossier,B.C. and Lifton,R.P.
  TITLE     Mutations in subunits of the epithelial sodium channel cause salt
            wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1
  JOURNAL   Nat Genet 12 (3), 248-253 (1996)
   PUBMED   8589714
REFERENCE   8  (residues 1 to 669)
  AUTHORS   Meisler,M.H., Barrow,L.L., Canessa,C.M. and Rossier,B.C.
  TITLE     SCNN1, an epithelial cell sodium channel gene in the conserved
            linkage group on mouse chromosome 6 and human chromosome 12
  JOURNAL   Genomics 24 (1), 185-186 (1994)
   PUBMED   7896277
REFERENCE   9  (residues 1 to 669)
  AUTHORS   McDonald,F.J., Snyder,P.M., McCray,P.B. Jr. and Welsh,M.J.
  TITLE     Cloning, expression, and tissue distribution of a human
            amiloride-sensitive Na+ channel
  JOURNAL   Am J Physiol 266 (6 Pt 1), L728-L734 (1994)
   PUBMED   8023962
REFERENCE   10 (residues 1 to 669)
  AUTHORS   Voilley,N., Lingueglia,E., Champigny,G., Mattei,M.G., Waldmann,R.,
            Lazdunski,M. and Barbry,P.
  TITLE     The lung amiloride-sensitive Na+ channel: biophysical properties,
            pharmacology, ontogenesis, and molecular cloning
  JOURNAL   Proc Natl Acad Sci U S A 91 (1), 247-251 (1994)
   PUBMED   8278374
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB232484.1 and X76180.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: Nonvoltage-gated, amiloride-sensitive, sodium channels
            control fluid and electrolyte transport across epithelia in many
            organs. These channels are heteromeric complexes consisting of 3
            subunits: alpha, beta, and gamma. This gene encodes the alpha
            subunit, and mutations in this gene have been associated with
            pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease
            resulting from target organ unresponsiveness to mineralocorticoids.
            Alternatively spliced transcript variants encoding different
            isoforms have been described for this gene. [provided by RefSeq,
            Apr 2009].
            
            Transcript Variant: This variant (1, also known as alpha-ENaC1)
            represents the predominant transcript, and encodes isoform 1.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X76180.1, SRR11853564.6196.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000228916.7/ ENSP00000228916.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..669
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12p13.31"
     Protein         1..669
                     /product="epithelial sodium channel subunit alpha isoform
                     1"
                     /note="nasal epithelial sodium channel alpha subunit;
                     amiloride-sensitive sodium channel subunit alpha 2; sodium
                     channel epithelial 1 alpha subunit; alpha ENaC-2; ENaC
                     subunit alpha; epithelial sodium channel subunit alpha;
                     amiloride-sensitive epithelial sodium channel alpha
                     subunit; alpha-ENaC; alpha-NaCH; epithelial Na(+) channel
                     subunit alpha; nonvoltage-gated sodium channel 1 subunit
                     alpha; sodium channel, nonvoltage-gated 1 alpha; sodium
                     channel, non voltage gated 1 alpha subunit; sodium
                     channel, non-voltage-gated 1 alpha"
                     /calculated_mol_wt=75573
     Region          1..43
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P37088.1)"
     Region          54..647
                     /region_name="ENaC"
                     /note="sodium channel transporter; TIGR00859"
                     /db_xref="CDD:273304"
     Site            86..106
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P37088.1)"
     Region          175..243
                     /region_name="Gating release of inhibition by proteolysis
                     (GRIP), protease-sensitive region that is responsible for
                     the proteolytic activation of the channel.
                     /evidence=ECO:0000269|PubMed:30251954,
                     ECO:0000269|PubMed:32729833"
                     /note="propagated from UniProtKB/Swiss-Prot (P37088.1)"
     Site            178..179
                     /site_type="cleavage"
                     /note="Cleavage by Furin.
                     /evidence=ECO:0000250|UniProtKB:Q61180; propagated from
                     UniProtKB/Swiss-Prot (P37088.1)"
     Site            204..205
                     /site_type="cleavage"
                     /note="Cleavage by Furin.
                     /evidence=ECO:0000250|UniProtKB:Q61180; propagated from
                     UniProtKB/Swiss-Prot (P37088.1)"
     Site            563..583
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P37088.1)"
     Region          620..669
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P37088.1)"
     Region          640..644
                     /region_name="PY motif, recruits WW domain-containing
                     proteins and is thereby required for ubiquitination and
                     inhibition of the channel by NEDD4 and NEDD4L.
                     /evidence=ECO:0000269|PubMed:17502380,
                     ECO:0000269|PubMed:23665454"
                     /note="propagated from UniProtKB/Swiss-Prot (P37088.1)"
     CDS             1..669
                     /gene="SCNN1A"
                     /gene_synonym="BESC2; ENaCa; ENaCalpha; LIDLS3; PHA1B1;
                     SCNEA; SCNN1"
                     /coded_by="NM_001038.6:114..2123"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS8543.1"
                     /db_xref="GeneID:6337"
                     /db_xref="HGNC:HGNC:10599"
                     /db_xref="MIM:600228"
ORIGIN      
        1 megnkleeqd ssppqstpgl mkgnkreeqg lgpepaapqq ptaeeealie fhrsyrelfe
       61 ffcnnttihg airlvcsqhn rmktafwavl wlctfgmmyw qfgllfgeyf sypvslninl
      121 nsdklvfpav tictlnpyry peikeeleel driteqtlfd lykyssfttl vagsrsrrdl
      181 rgtlphplqr lrvpppphga rrarsvassl rdnnpqvdwk dwkigfqlcn qnksdcfyqt
      241 yssgvdavre wyrfhyinil srlpetlpsl eedtlgnfif acrfnqvscn qanyshfhhp
      301 mygncytfnd knnsnlwmss mpginnglsl mlraeqndfi pllstvtgar vmvhgqdepa
      361 fmddggfnlr pgvetsismr ketldrlggd ygdctkngsd vpvenlypsk ytqqvcihsc
      421 fqesmikecg cayifyprpq nveycdyrkh sswgycyykl qvdfssdhlg cftkcrkpcs
      481 vtsyqlsagy srwpsvtsqe wvfqmlsrqn nytvnnkrng vakvniffke lnyktnsesp
      541 svtmvtllsn lgsqwslwfg ssvlsvvema elvfdllvim flmllrrfrs rywspgrggr
      601 gaqevastla ssppshfcph pmslslsqpg papspaltap ppayatlgpr pspggsagas
      661 sstcplggp
//
