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P37088 (SCNNA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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
Short name=ENaCA
Nonvoltage-gated sodium channel 1 subunit alpha
SCNEA
Gene names
Name:SCNN1A
Synonyms:SCNN1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length669 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. Ref.22

Enzyme regulation

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

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). Ref.15 Ref.16 Ref.17 Ref.21 Ref.22 Ref.26

Subcellular location

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. Ref.20 Ref.22

Tissue specificity

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. Ref.14 Ref.20

Induction

By aldosterone. Ref.12

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.

Involvement in disease

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.
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 (Ref.19). Ref.19 Ref.28 Ref.31

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.33

Sequence similarities

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

Sequence caution

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

Ontologies

Keywords
   Biological processIon transport
Sensory transduction
Sodium transport
Taste
Transport
   Cellular componentCell membrane
Cell projection
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
   PTMGlycoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processexcretion

Traceable author statement PubMed 8589714. Source: ProtInc

ion transmembrane transport

Traceable author statement. Source: Reactome

multicellular organismal water homeostasis

Inferred from direct assay Ref.22. 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 direct assay Ref.22. Source: UniProtKB

sodium ion transmembrane transport

Inferred from direct assay Ref.22. Source: UniProtKB

sodium ion transport

Traceable author statement PubMed 8589714. Source: ProtInc

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from direct assay Ref.20. Source: UniProtKB

ciliary membrane

Inferred from direct assay Ref.20. Source: UniProtKB

cortical actin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 15326289. Source: UniProt

integral component of plasma membrane

Inferred from direct assay Ref.22. Source: UniProtKB

motile cilium

Inferred from direct assay Ref.20. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

sodium channel complex

Inferred from direct assay Ref.22. Source: UniProtKB

   Molecular_functionWW domain binding

Inferred from physical interaction PubMed 10642508. Source: BHF-UCL

ligand-gated sodium channel activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.16Ref.21. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P37088-1)

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.
Isoform 2 (identifier: P37088-2)

Also known as: Alpha ENAC2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGMARGSLTRVPGVMGEGTQGPELSLDPDPCSPQSTPGLMKGNKLEEQDPRPLQPIPGLM
Isoform 3 (identifier: P37088-3)

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.
Isoform 4 (identifier: P37088-4)

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.
Isoform 5 (identifier: P37088-5)

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.
Isoform 6 (identifier: P37088-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSSIKGNKLEEQDPRPLQPIPGLM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 669669Amiloride-sensitive sodium channel subunit alpha
PRO_0000181261

Regions

Topological domain1 – 8686Cytoplasmic By similarity
Transmembrane87 – 11024Helical; By similarity
Topological domain111 – 543433Extracellular By similarity
Transmembrane544 – 57431Helical; By similarity
Topological domain575 – 66995Cytoplasmic By similarity

Amino acid modifications

Glycosylation2321N-linked (GlcNAc...) Potential
Glycosylation2931N-linked (GlcNAc...) Potential
Glycosylation3121N-linked (GlcNAc...) Potential
Glycosylation3971N-linked (GlcNAc...) Potential
Glycosylation5111N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence11M → MGMARGSLTRVPGVMGEGTQ GPELSLDPDPCSPQSTPGLM KGNKLEEQDPRPLQPIPGLM in isoform 2.
VSP_007719
Alternative sequence11M → MSSIKGNKLEEQDPRPLQPI PGLM in isoform 6.
VSP_043667
Alternative sequence229 – 24517CNQNK…YSSGV → ELLSLPPPDVWKLLYFG in isoform 3.
VSP_007720
Alternative sequence246 – 669424Missing in isoform 3.
VSP_007721
Alternative sequence327 – 34519Missing in isoform 4.
VSP_007722
Alternative sequence4541G → GQVRSLTPVIPALWEAEAGG SRG in isoform 5.
VSP_007723
Natural variant611F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. Ref.33
Corresponds to variant rs61758859 [ dbSNP | Ensembl ].
VAR_060793
Natural variant1141V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. Ref.33
Corresponds to variant rs61759861 [ dbSNP | Ensembl ].
VAR_060794
Natural variant1811R → W Functional polymorphism; significant increase of amiloride-sensitive sodium currents. Ref.32 Ref.33
Corresponds to variant rs55797039 [ dbSNP | Ensembl ].
VAR_060795
Natural variant3271G → C in PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents. Ref.19 Ref.31
VAR_026518
Natural variant3341A → T Functional polymorphism; significant decrease of amiloride-sensitive sodium currents. Ref.24 Ref.33
Corresponds to variant rs11542844 [ dbSNP | Ensembl ].
VAR_060796
Natural variant4021P → H.
Corresponds to variant rs13306616 [ dbSNP | Ensembl ].
VAR_052035
Natural variant4931W → 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. Ref.28 Ref.30 Ref.33
Corresponds to variant rs5742912 [ dbSNP | Ensembl ].
VAR_015833
Natural variant5621S → L in PHA1B. Ref.28
VAR_015834
Natural variant5731V → I.
Corresponds to variant rs59142484 [ dbSNP | Ensembl ].
VAR_060797
Natural variant6181C → F. Ref.24
Corresponds to variant rs3741913 [ dbSNP | Ensembl ].
VAR_022142
Natural variant6631T → A. Ref.5 Ref.10 Ref.24 Ref.27 Ref.29 Ref.30 Ref.33
Corresponds to variant rs2228576 [ dbSNP | Ensembl ].
VAR_015835

Secondary structure

... 669
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha ENAC1) [UniParc].

Last modified October 1, 1994. Version 1.
Checksum: 2CCF342E7DF32E72

FASTA66975,704
        10         20         30         40         50         60 
MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE FHRSYRELFE 

        70         80         90        100        110        120 
FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW QFGLLFGEYF SYPVSLNINL 

       130        140        150        160        170        180 
NSDKLVFPAV TICTLNPYRY PEIKEELEEL DRITEQTLFD LYKYSSFTTL VAGSRSRRDL 

       190        200        210        220        230        240 
RGTLPHPLQR LRVPPPPHGA RRARSVASSL RDNNPQVDWK DWKIGFQLCN QNKSDCFYQT 

       250        260        270        280        290        300 
YSSGVDAVRE WYRFHYINIL SRLPETLPSL EEDTLGNFIF ACRFNQVSCN QANYSHFHHP 

       310        320        330        340        350        360 
MYGNCYTFND KNNSNLWMSS MPGINNGLSL MLRAEQNDFI PLLSTVTGAR VMVHGQDEPA 

       370        380        390        400        410        420 
FMDDGGFNLR PGVETSISMR KETLDRLGGD YGDCTKNGSD VPVENLYPSK YTQQVCIHSC 

       430        440        450        460        470        480 
FQESMIKECG CAYIFYPRPQ NVEYCDYRKH SSWGYCYYKL QVDFSSDHLG CFTKCRKPCS 

       490        500        510        520        530        540 
VTSYQLSAGY SRWPSVTSQE WVFQMLSRQN NYTVNNKRNG VAKVNIFFKE LNYKTNSESP 

       550        560        570        580        590        600 
SVTMVTLLSN LGSQWSLWFG SSVLSVVEMA ELVFDLLVIM FLMLLRRFRS RYWSPGRGGR 

       610        620        630        640        650        660 
GAQEVASTLA SSPPSHFCPH PMSLSLSQPG PAPSPALTAP PPAYATLGPR PSPGGSAGAS 


SSTCPLGGP 

« Hide

Isoform 2 (Alpha ENAC2) [UniParc].

Checksum: 206613374DFB1800
Show »

FASTA72881,856
Isoform 3 (Alpha ENACx) [UniParc].

Checksum: FFDC0622FFA37329
Show »

FASTA24528,328
Isoform 4 (Alpha ENAC-19) [UniParc].

Checksum: 5866D42CCAF6F8B4
Show »

FASTA65073,603
Isoform 5 (Alpha ENAC+22) [UniParc].

Checksum: 07B981FBE74AE30B
Show »

FASTA69177,980
Isoform 6 [UniParc].

Checksum: 3AD7710E69D1BE54
Show »

FASTA69278,234

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]Erratum
Ambrosius W.T., Bloem L.J., Zhou L., Rebhun J.F., Snyder P.M., Wagner M.A., Guo C., Pratt J.H.
Hypertension 41:1E-1E(2003)
[26]"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.
[27]"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.
[28]"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.
[29]"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.
[30]"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.
[31]"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.
[32]"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.
[33]"Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease."
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. expand/collapse author list , Stuhrmann M., Schwarz M., Skalicka V., de Monestrol I., Girodon E., Ferec C., Claustres M., Tuemmler B., Cassiman J.-J., Korbmacher C., Cuppens H.
Hum. Mutat. 30:1093-1103(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X76180 mRNA. Translation: CAA53773.1.
L29007 Genomic DNA. Translation: AAA21813.1.
Z92978 expand/collapse EMBL AC list , Z92979, Z92980, Z92981 Genomic DNA. Translation: CAB07505.1.
AF060913 expand/collapse EMBL AC list , 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.
CCDSCCDS53738.1. [P37088-2]
CCDS53739.1. [P37088-6]
CCDS8543.1. [P37088-1]
PIRA49585.
RefSeqNP_001029.1. NM_001038.5. [P37088-1]
NP_001153047.1. NM_001159575.1. [P37088-6]
NP_001153048.1. NM_001159576.1. [P37088-2]
UniGeneHs.591047.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2M3ONMR-P638-648[»]
ProteinModelPortalP37088.
SMRP37088. Positions 279-566.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112241. 20 interactions.
MINTMINT-198663.
STRING9606.ENSP00000228916.

Chemistry

BindingDBP37088.
ChEMBLCHEMBL1791.
DrugBankDB00594. Amiloride.
DB00384. Triamterene.

Protein family/group databases

TCDB1.A.6.1.1. the epithelial na(+) channel (enac) family.

PTM databases

PhosphoSiteP37088.

Polymorphism databases

DMDM585966.

Proteomic databases

PaxDbP37088.
PRIDEP37088.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000228916; ENSP00000228916; ENSG00000111319. [P37088-1]
ENST00000360168; ENSP00000353292; ENSG00000111319. [P37088-2]
ENST00000543768; ENSP00000438739; ENSG00000111319. [P37088-6]
GeneID6337.
KEGGhsa:6337.
UCSCuc001qnv.3. human. [P37088-1]
uc001qnw.3. human. [P37088-2]
uc010sfb.2. human. [P37088-6]

Organism-specific databases

CTD6337.
GeneCardsGC12M006456.
HGNCHGNC:10599. SCNN1A.
HPAHPA012743.
HPA012939.
MIM264350. phenotype.
600228. gene.
613021. phenotype.
neXtProtNX_P37088.
Orphanet171876. Generalized pseudohypoaldosteronism type 1.
60033. Idiopathic bronchiectasis.
PharmGKBPA305.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG288544.
HOGENOMHOG000236286.
HOVERGENHBG058435.
InParanoidP37088.
KOK04824.
OMASRQNNYT.
OrthoDBEOG7T1R9N.
PhylomeDBP37088.
TreeFamTF330663.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP37088.
BgeeP37088.
CleanExHS_SCNN1A.
GenevestigatorP37088.

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

ChiTaRSSCNN1A. human.
GeneWikiSCNN1A.
GenomeRNAi6337.
NextBio24608.
PROP37088.
SOURCESearch...

Entry information

Entry nameSCNNA_HUMAN
AccessionPrimary (citable) accession number: P37088
Secondary accession number(s): A5X2U9 expand/collapse secondary AC list , B4E2Q5, C5HTZ0, O43271, Q6GSQ6, Q9UM64
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: July 9, 2014
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM