Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Amiloride-sensitive sodium channel subunit alpha

Gene

SCNN1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 eccrine sweat glands. Also plays a role in taste perception.3 Publications

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

  • ligand-gated sodium channel activity Source: InterPro
  • WW domain binding Source: BHF-UCL

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionIon channel, Sodium channel
Biological processIon transport, Sensory transduction, Sodium transport, Taste, Transport
LigandSodium

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-2672351 Stimuli-sensing channels

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P37088

Protein family/group databases

Transport Classification Database

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

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SCNN1A
Synonyms:SCNN1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 12

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...
EuPathDBi
HostDB:ENSG00000111319.12

Human Gene Nomenclature Database

More...
HGNCi
HGNC:10599 SCNN1A

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
600228 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P37088

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 85CytoplasmicBy similarityAdd BLAST85
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei86 – 106Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini107 – 562ExtracellularBy similarityAdd BLAST456
Transmembranei563 – 583Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini584 – 669CytoplasmicBy similarityAdd BLAST86

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Cytoplasm, Cytoplasmic vesicle, Flagellum, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Pseudohypoaldosteronism 1, autosomal recessive (PHA1B)3 Publications
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
Disease descriptionA 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.
See also OMIM:264350
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_026518327G → 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 PublicationsCorresponds to variant dbSNP:rs974854786Ensembl.1
Natural variantiVAR_015834562S → L in PHA1B. 1 PublicationCorresponds to variant dbSNP:rs137852635EnsemblClinVar.1
Bronchiectasis with or without elevated sweat chloride 2 (BESC2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613021
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06079361F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. 1 PublicationCorresponds to variant dbSNP:rs61758859Ensembl.1
Natural variantiVAR_060794114V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. 1 PublicationCorresponds to variant dbSNP:rs61759861EnsemblClinVar.1
Liddle syndrome 3 (LIDLS3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Liddle syndrome, an autosomal dominant disorder characterized by early onset of hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion.
See also OMIM:618126
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_081179479C → R in LIDLS3; increased channel activity. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi394C → S: Increased channel activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
6337

MalaCards human disease database

More...
MalaCardsi
SCNN1A
MIMi264350 phenotype
613021 phenotype
618126 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000111319

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
171876 Generalized pseudohypoaldosteronism type 1
60033 Idiopathic bronchiectasis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA305

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL1791

Drug and drug target database

More...
DrugBanki
DB00594 Amiloride
DB00384 Triamterene

IUPHAR/BPS Guide to PHARMACOLOGY

More...
GuidetoPHARMACOLOGYi
738

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
SCNN1A

Domain mapping of disease mutations (DMDM)

More...
DMDMi
585966

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001812611 – 669Amiloride-sensitive sodium channel subunit alphaAdd BLAST669

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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
N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
P37088

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
P37088

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P37088

PeptideAtlas

More...
PeptideAtlasi
P37088

PRoteomics IDEntifications database

More...
PRIDEi
P37088

ProteomicsDB human proteome resource

More...
ProteomicsDBi
55257
55258 [P37088-2]
55259 [P37088-3]
55260 [P37088-4]
55261 [P37088-5]
55262 [P37088-6]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P37088

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P37088

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in the female reproductive tract, from the fimbrial end of the fallopian tube to the endometrium (at protein level) (PubMed:22207244). 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 (PubMed:22207244). in skin, expressed in keratinocytes, melanocytes and Merkel cells of the epidermal sub-layers, stratum basale, stratum spinosum and stratum granulosum (at protein level) (PubMed:28130590). Expressed in the outer root sheath of the hair follicles (at protein level) (PubMed:28130590). Detected in both peripheral and central cells of the sebaceous gland (at protein level) (PubMed:28130590). Expressed by eccrine sweat glands (at protein level) (PubMed:28130590). In skin, also expressed by arrector pili muscle cells and intradermal adipocytes (PubMed:28130590). 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 (PubMed:9575806).3 Publications

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

By aldosterone.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000111319 Expressed in 228 organ(s), highest expression level in nasal cavity epithelium

CleanEx database of gene expression profiles

More...
CleanExi
HS_SCNN1A

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P37088 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P37088 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA012743

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in some organisms and can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties (By similarity). Interacts with NEDD4 (via WW domains) (PubMed:11244092, PubMed:11696533, PubMed:12167593, PubMed:23665454). Interacts with NEDD4L (via WW domains) (PubMed:11244092, PubMed:11696533). Interacts with WWP1 (via WW domains) (PubMed:9169421). Interacts with WWP2 (via WW domains) (PubMed:12167593, PubMed:9169421). Interacts with the full-length immature form of PCSK9 (pro-PCSK9) (PubMed:22493497).By similarity6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
SCNN1GP511703EBI-7845444,EBI-2547354

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
112241, 25 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...
ComplexPortali
CPX-2188 Amiloride-sensitive sodium channel complex, alpha-beta-gamma
CPX-312 Amiloride-sensitive sodium channel complex, delta-alpha-beta-gamma

CORUM comprehensive resource of mammalian protein complexes

More...
CORUMi
P37088

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...
ELMi
P37088

Protein interaction database and analysis system

More...
IntActi
P37088, 3 interactors

Molecular INTeraction database

More...
MINTi
P37088

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000353292

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P37088

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1669
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M3ONMR-P638-648[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

More...
ProteinModelPortali
P37088

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
P37088

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG4294 Eukaryota
ENOG410ZNFK LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000160952

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000236286

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG058435

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P37088

KEGG Orthology (KO)

More...
KOi
K04824

Identification of Orthologs from Complete Genome Data

More...
OMAi
QVCIRSC

Database of Orthologous Groups

More...
OrthoDBi
1305393at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P37088

TreeFam database of animal gene trees

More...
TreeFami
TF330663

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR001873 ENaC
IPR004724 ENaC_chordates
IPR020903 ENaC_CS

The PANTHER Classification System

More...
PANTHERi
PTHR11690 PTHR11690, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00858 ASC, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR01078 AMINACHANNEL

TIGRFAMs; a protein family database

More...
TIGRFAMsi
TIGR00859 ENaC, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS01206 ASC, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (6+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 6 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 6 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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
        10         20         30         40         50
MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE
60 70 80 90 100
FHRSYRELFE FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW
110 120 130 140 150
QFGLLFGEYF SYPVSLNINL NSDKLVFPAV TICTLNPYRY PEIKEELEEL
160 170 180 190 200
DRITEQTLFD LYKYSSFTTL VAGSRSRRDL RGTLPHPLQR LRVPPPPHGA
210 220 230 240 250
RRARSVASSL RDNNPQVDWK DWKIGFQLCN QNKSDCFYQT YSSGVDAVRE
260 270 280 290 300
WYRFHYINIL SRLPETLPSL EEDTLGNFIF ACRFNQVSCN QANYSHFHHP
310 320 330 340 350
MYGNCYTFND KNNSNLWMSS MPGINNGLSL MLRAEQNDFI PLLSTVTGAR
360 370 380 390 400
VMVHGQDEPA FMDDGGFNLR PGVETSISMR KETLDRLGGD YGDCTKNGSD
410 420 430 440 450
VPVENLYPSK YTQQVCIHSC FQESMIKECG CAYIFYPRPQ NVEYCDYRKH
460 470 480 490 500
SSWGYCYYKL QVDFSSDHLG CFTKCRKPCS VTSYQLSAGY SRWPSVTSQE
510 520 530 540 550
WVFQMLSRQN NYTVNNKRNG VAKVNIFFKE LNYKTNSESP SVTMVTLLSN
560 570 580 590 600
LGSQWSLWFG SSVLSVVEMA ELVFDLLVIM FLMLLRRFRS RYWSPGRGGR
610 620 630 640 650
GAQEVASTLA SSPPSHFCPH PMSLSLSQPG PAPSPALTAP PPAYATLGPR
660
PSPGGSAGAS SSTCPLGGP
Length:669
Mass (Da):75,704
Last modified:October 1, 1994 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C5HTZ1C5HTZ1_HUMAN
Amiloride-sensitive sodium channel ...
SCNN1A
245Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
J3KPV6J3KPV6_HUMAN
Amiloride-sensitive sodium channel ...
SCNN1A
511Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5H5F8F5H5F8_HUMAN
Amiloride-sensitive sodium channel ...
SCNN1A
159Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5GXE6F5GXE6_HUMAN
Amiloride-sensitive sodium channel ...
SCNN1A
369Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06079361F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. 1 PublicationCorresponds to variant dbSNP:rs61758859Ensembl.1
Natural variantiVAR_060794114V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. 1 PublicationCorresponds to variant dbSNP:rs61759861EnsemblClinVar.1
Natural variantiVAR_060795181R → W Functional polymorphism; significant increase of amiloride-sensitive sodium currents. 2 PublicationsCorresponds to variant dbSNP:rs55797039EnsemblClinVar.1
Natural variantiVAR_026518327G → 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 PublicationsCorresponds to variant dbSNP:rs974854786Ensembl.1
Natural variantiVAR_060796334A → T Functional polymorphism; significant decrease of amiloride-sensitive sodium currents. 2 PublicationsCorresponds to variant dbSNP:rs11542844EnsemblClinVar.1
Natural variantiVAR_052035402P → H. Corresponds to variant dbSNP:rs13306616Ensembl.1
Natural variantiVAR_081179479C → R in LIDLS3; increased channel activity. 1 Publication1
Natural variantiVAR_015833493W → R Functional polymorphism; results in a 4-fold increase of amiloride-sensitive sodium currents; found in BESC2 patients at higher frequency than in controls; associated with an increased risk for ischemic cerebrovascular events. 2 PublicationsCorresponds to variant dbSNP:rs5742912EnsemblClinVar.1
Natural variantiVAR_015834562S → L in PHA1B. 1 PublicationCorresponds to variant dbSNP:rs137852635EnsemblClinVar.1
Natural variantiVAR_060797573V → I. Corresponds to variant dbSNP:rs59142484Ensembl.1
Natural variantiVAR_022142618C → F1 PublicationCorresponds to variant dbSNP:rs3741913EnsemblClinVar.1
Natural variantiVAR_015835663T → A7 PublicationsCorresponds to variant dbSNP:rs2228576EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0077191M → MGMARGSLTRVPGVMGEGTQ GPELSLDPDPCSPQSTPGLM KGNKLEEQDPRPLQPIPGLM in isoform 2. Curated1
Alternative sequenceiVSP_0436671M → MSSIKGNKLEEQDPRPLQPI PGLM in isoform 6. 1 Publication1
Alternative sequenceiVSP_007720229 – 245CNQNK…YSSGV → ELLSLPPPDVWKLLYFG in isoform 3. CuratedAdd BLAST17
Alternative sequenceiVSP_007721246 – 669Missing in isoform 3. CuratedAdd BLAST424
Alternative sequenceiVSP_007722327 – 345Missing in isoform 4. CuratedAdd BLAST19
Alternative sequenceiVSP_007723454G → GQVRSLTPVIPALWEAEAGG SRG in isoform 5. Curated1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
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

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS53738.1 [P37088-2]
CCDS53739.1 [P37088-6]
CCDS8543.1 [P37088-1]

Protein sequence database of the Protein Information Resource

More...
PIRi
A49585

NCBI Reference Sequences

More...
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]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.591047

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000228916; ENSP00000228916; ENSG00000111319 [P37088-1]
ENST00000360168; ENSP00000353292; ENSG00000111319 [P37088-2]
ENST00000543768; ENSP00000438739; ENSG00000111319 [P37088-6]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
6337

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:6337

UCSC genome browser

More...
UCSCi
uc001qnw.3 human [P37088-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M3ONMR-P638-648[»]
ProteinModelPortaliP37088
SMRiP37088
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112241, 25 interactors
ComplexPortaliCPX-2188 Amiloride-sensitive sodium channel complex, alpha-beta-gamma
CPX-312 Amiloride-sensitive sodium channel complex, delta-alpha-beta-gamma
CORUMiP37088
ELMiP37088
IntActiP37088, 3 interactors
MINTiP37088
STRINGi9606.ENSP00000353292

Chemistry databases

BindingDBiP37088
ChEMBLiCHEMBL1791
DrugBankiDB00594 Amiloride
DB00384 Triamterene
GuidetoPHARMACOLOGYi738

Protein family/group databases

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

PTM databases

iPTMnetiP37088
PhosphoSitePlusiP37088

Polymorphism and mutation databases

BioMutaiSCNN1A
DMDMi585966

Proteomic databases

EPDiP37088
jPOSTiP37088
PaxDbiP37088
PeptideAtlasiP37088
PRIDEiP37088
ProteomicsDBi55257
55258 [P37088-2]
55259 [P37088-3]
55260 [P37088-4]
55261 [P37088-5]
55262 [P37088-6]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000228916; ENSP00000228916; ENSG00000111319 [P37088-1]
ENST00000360168; ENSP00000353292; ENSG00000111319 [P37088-2]
ENST00000543768; ENSP00000438739; ENSG00000111319 [P37088-6]
GeneIDi6337
KEGGihsa:6337
UCSCiuc001qnw.3 human [P37088-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
6337
DisGeNETi6337
EuPathDBiHostDB:ENSG00000111319.12

GeneCards: human genes, protein and diseases

More...
GeneCardsi
SCNN1A
HGNCiHGNC:10599 SCNN1A
HPAiHPA012743
MalaCardsiSCNN1A
MIMi264350 phenotype
600228 gene
613021 phenotype
618126 phenotype
neXtProtiNX_P37088
OpenTargetsiENSG00000111319
Orphaneti171876 Generalized pseudohypoaldosteronism type 1
60033 Idiopathic bronchiectasis
PharmGKBiPA305

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4294 Eukaryota
ENOG410ZNFK LUCA
GeneTreeiENSGT00940000160952
HOGENOMiHOG000236286
HOVERGENiHBG058435
InParanoidiP37088
KOiK04824
OMAiQVCIRSC
OrthoDBi1305393at2759
PhylomeDBiP37088
TreeFamiTF330663

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
SIGNORiP37088

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
SCNN1A human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
SCNN1A

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
6337

Protein Ontology

More...
PROi
PR:P37088

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000111319 Expressed in 228 organ(s), highest expression level in nasal cavity epithelium
CleanExiHS_SCNN1A
ExpressionAtlasiP37088 baseline and differential
GenevisibleiP37088 HS

Family and domain databases

InterProiView protein in InterPro
IPR001873 ENaC
IPR004724 ENaC_chordates
IPR020903 ENaC_CS
PANTHERiPTHR11690 PTHR11690, 1 hit
PfamiView protein in Pfam
PF00858 ASC, 1 hit
PRINTSiPR01078 AMINACHANNEL
TIGRFAMsiTIGR00859 ENaC, 1 hit
PROSITEiView protein in PROSITE
PS01206 ASC, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSCNNA_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P37088
Secondary accession number(s): A5X2U9
, B4E2Q5, C5HTZ0, O43271, Q6GSQ6, Q9UM64
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: January 16, 2019
This is version 197 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again