Amiloride-sensitive sodium channel subunit alpha

<p>Provides any useful information about the protein, mostly biological knowledge.</p><p><a href='../manual/function_section' target='_top'>More...</a></p>Functionⁱ

<p>Describes an enzyme regulatory mechanism and reports the components which regulate (by activation or inhibition) the reaction.</p><p><a href='../manual/enzyme_regulation' target='_top'>More...</a></p>Enzyme regulationⁱ

<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><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

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

  <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ

  • 10642508

<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><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Biological processⁱ

• ion transmembrane transport Source: Reactome
• multicellular organismal water homeostasis Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 24124190

• response to stimulus Source: UniProtKB-KW
• sensory perception of taste Source: UniProtKB-KW
• sodium ion homeostasis Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 24124190

• sodium ion transmembrane transport Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 24124190

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Molecular functionⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Biological processⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Ligandⁱ

Enzyme and pathway databases

Protein family/group databases

<p>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><p><a href='../manual/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

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

Topology

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.</p><p><a href='../manual/topo_dom' target='_top'>More...</a></p>Topological domaini	1 – 85	85	CytoplasmicBy similarity <p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More…</a></p> Manual assertion inferred from sequence similarity toi UniProtKB:P37089 (SCNNA_RAT)			Add BLAST
<p>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><p><a href='../manual/transmem' target='_top'>More...</a></p>Transmembranei	86 – 106	21	Helical; Name=1Sequence analysis			Add BLAST
<p>Describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.</p><p><a href='../manual/topo_dom' target='_top'>More...</a></p>Topological domaini	107 – 562	456	ExtracellularBy similarity <p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More…</a></p> Manual assertion inferred from sequence similarity toi UniProtKB:P37089 (SCNNA_RAT)			Add BLAST
<p>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><p><a href='../manual/transmem' target='_top'>More...</a></p>Transmembranei	563 – 583	21	Helical; Name=2Sequence analysis			Add BLAST
<p>Describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.</p><p><a href='../manual/topo_dom' target='_top'>More...</a></p>Topological domaini	584 – 669	86	CytoplasmicBy similarity <p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More…</a></p> Manual assertion inferred from sequence similarity toi UniProtKB:P37089 (SCNNA_RAT)			Add BLAST

<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><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Cellular componentⁱ

• apical plasma membrane Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 22207244

• ciliary membrane Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 22207244

• cortical actin cytoskeleton Source: Ensembl
• extracellular exosome Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 15326289

• integral component of plasma membrane Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 24124190

• motile cilium Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 22207244

• plasma membrane Source: Reactome
• sodium channel complex Source: UniProtKB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 24124190

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Cellular componentⁱ

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

<p>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"><span class="caps">OMIM</span></a> database are represented with a <a href="/diseases">controlled vocabulary</a> in the following way:</p><p><a href='../manual/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Pseudohypoaldosteronism 1, autosomal recessive (PHA1B)3 Publications

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.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.
• Ref.29

  "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.
• Ref.32

  "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.

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

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.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.

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 key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	327 – 327	1	G → C in PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Ref.32 "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.		VAR_026518
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	562 – 562	1	S → L in PHA1B. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.29 "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. Corresponds to variant rs137852635 [ dbSNP | Ensembl ].		VAR_015834

Bronchiectasis with or without elevated sweat chloride 2 (BESC2)1 Publication

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.34

  "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.

  , 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.

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 key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	61 – 61	1	F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.34 "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. , 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. Corresponds to variant rs61758859 [ dbSNP | Ensembl ].		VAR_060793
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	114 – 114	1	V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.34 "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. , 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. Corresponds to variant rs61759861 [ dbSNP | Ensembl ].		VAR_060794
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	493 – 493	1	W → 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 incresed risk for ischemic cerebrovascular events. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.29 "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. Ref.34 "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. , 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. Corresponds to variant rs5742912 [ dbSNP | Ensembl ].		VAR_015833

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Diseaseⁱ

Organism-specific databases

Chemistry

Polymorphism and mutation databases

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

Molecule processing

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the extent of a polypeptide chain in the mature protein following processing.</p><p><a href='../manual/chain' target='_top'>More...</a></p>Chaini	1 – 669	669	Amiloride-sensitive sodium channel subunit alpha		PRO_0000181261	Add BLAST

<p>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><p><a href='../manual/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - PTMⁱ

Proteomic databases

PTM databases

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

<p>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 />Examples: <a href="/uniprot/P92958#expression"><span class="caps">P92958</span></a>, <a href="/uniprot/Q8TDN4#expression"><span class="caps">Q8TDN4</span></a>, <a href="/uniprot/O14734#expression"><span class="caps">O14734</span></a></p><p><a href='../manual/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

<p>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><p><a href='../manual/induction' target='_top'>More...</a></p>Inductionⁱ

Gene expression databases

Organism-specific databases

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

<p>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="/help/function_section">‘Function’</a> section).</p><p><a href='../manual/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>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><p><a href='../manual/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

<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><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• WW domain binding Source: BHF-UCL

  <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ

  • 10642508

Protein-protein interaction databases

Chemistry

<p>Provides information on the tertiary and secondary structure of a protein.</p><p><a href='../manual/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	644 – 647	4	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:2M3O

3D structure databases

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

<p>Provides information about the sequence similarity with other proteins.</p><p><a href='../manual/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>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 length and molecular weight.</p><p><a href='../manual/sequences_section' target='_top'>More...</a></p>Sequences (6)ⁱ

<p>Indicates if the <a href="/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.</p><p><a href='../manual/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry describes 6<p>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><p><a href='../manual/alternative_products' target='_top'>More...</a></p> isoformsⁱ produced by alternative splicing. AlignAdd to basketAdded to basket

        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                                  

        10         20         30         40         50
MGMARGSLTR VPGVMGEGTQ GPELSLDPDP CSPQSTPGLM KGNKLEEQDP 
        60         70         80         90        100
RPLQPIPGLM EGNKLEEQDS SPPQSTPGLM KGNKREEQGL GPEPAAPQQP 
       110        120        130        140        150
TAEEEALIEF HRSYRELFEF FCNNTTIHGA IRLVCSQHNR MKTAFWAVLW 
       160        170        180        190        200
LCTFGMMYWQ FGLLFGEYFS YPVSLNINLN SDKLVFPAVT ICTLNPYRYP 
       210        220        230        240        250
EIKEELEELD RITEQTLFDL YKYSSFTTLV AGSRSRRDLR GTLPHPLQRL 
       260        270        280        290        300
RVPPPPHGAR RARSVASSLR DNNPQVDWKD WKIGFQLCNQ NKSDCFYQTY 
       310        320        330        340        350
SSGVDAVREW YRFHYINILS RLPETLPSLE EDTLGNFIFA CRFNQVSCNQ 
       360        370        380        390        400
ANYSHFHHPM YGNCYTFNDK NNSNLWMSSM PGINNGLSLM LRAEQNDFIP 
       410        420        430        440        450
LLSTVTGARV MVHGQDEPAF MDDGGFNLRP GVETSISMRK ETLDRLGGDY 
       460        470        480        490        500
GDCTKNGSDV PVENLYPSKY TQQVCIHSCF QESMIKECGC AYIFYPRPQN 
       510        520        530        540        550
VEYCDYRKHS SWGYCYYKLQ VDFSSDHLGC FTKCRKPCSV TSYQLSAGYS 
       560        570        580        590        600
RWPSVTSQEW VFQMLSRQNN YTVNNKRNGV AKVNIFFKEL NYKTNSESPS 
       610        620        630        640        650
VTMVTLLSNL GSQWSLWFGS SVLSVVEMAE LVFDLLVIMF LMLLRRFRSR 
       660        670        680        690        700
YWSPGRGGRG AQEVASTLAS SPPSHFCPHP MSLSLSQPGP APSPALTAPP 
       710        720 
PAYATLGPRP SPGGSAGASS STCPLGGP                       

        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 
RRARSVASSL RDNNPQVDWK DWKIGFQLEL LSLPPPDVWK LLYFG 

        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 MPGINNVTGA RVMVHGQDEP AFMDDGGFNL 
       360        370        380        390        400
RPGVETSISM RKETLDRLGG DYGDCTKNGS DVPVENLYPS KYTQQVCIHS 
       410        420        430        440        450
CFQESMIKEC GCAYIFYPRP QNVEYCDYRK HSSWGYCYYK LQVDFSSDHL 
       460        470        480        490        500
GCFTKCRKPC SVTSYQLSAG YSRWPSVTSQ EWVFQMLSRQ NNYTVNNKRN 
       510        520        530        540        550
GVAKVNIFFK ELNYKTNSES PSVTMVTLLS NLGSQWSLWF GSSVLSVVEM 
       560        570        580        590        600
AELVFDLLVI MFLMLLRRFR SRYWSPGRGG RGAQEVASTL ASSPPSHFCP 
       610        620        630        640        650
HPMSLSLSQP GPAPSPALTA PPPAYATLGP RPSPGGSAGA SSSTCPLGGP 

        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
SSWGQVRSLT PVIPALWEAE AGGSRGYCYY KLQVDFSSDH LGCFTKCRKP 
       510        520        530        540        550
CSVTSYQLSA GYSRWPSVTS QEWVFQMLSR QNNYTVNNKR NGVAKVNIFF 
       560        570        580        590        600
KELNYKTNSE SPSVTMVTLL SNLGSQWSLW FGSSVLSVVE MAELVFDLLV 
       610        620        630        640        650
IMFLMLLRRF RSRYWSPGRG GRGAQEVAST LASSPPSHFC PHPMSLSLSQ 
       660        670        680        690 
PGPAPSPALT APPPAYATLG PRPSPGGSAG ASSSTCPLGG P 

        10         20         30         40         50
MSSIKGNKLE EQDPRPLQPI PGLMEGNKLE EQDSSPPQST PGLMKGNKRE 
        60         70         80         90        100
EQGLGPEPAA PQQPTAEEEA LIEFHRSYRE LFEFFCNNTT IHGAIRLVCS 
       110        120        130        140        150
QHNRMKTAFW AVLWLCTFGM MYWQFGLLFG EYFSYPVSLN INLNSDKLVF 
       160        170        180        190        200
PAVTICTLNP YRYPEIKEEL EELDRITEQT LFDLYKYSSF TTLVAGSRSR 
       210        220        230        240        250
RDLRGTLPHP LQRLRVPPPP HGARRARSVA SSLRDNNPQV DWKDWKIGFQ 
       260        270        280        290        300
LCNQNKSDCF YQTYSSGVDA VREWYRFHYI NILSRLPETL PSLEEDTLGN 
       310        320        330        340        350
FIFACRFNQV SCNQANYSHF HHPMYGNCYT FNDKNNSNLW MSSMPGINNG 
       360        370        380        390        400
LSLMLRAEQN DFIPLLSTVT GARVMVHGQD EPAFMDDGGF NLRPGVETSI 
       410        420        430        440        450
SMRKETLDRL GGDYGDCTKN GSDVPVENLY PSKYTQQVCI HSCFQESMIK 
       460        470        480        490        500
ECGCAYIFYP RPQNVEYCDY RKHSSWGYCY YKLQVDFSSD HLGCFTKCRK 
       510        520        530        540        550
PCSVTSYQLS AGYSRWPSVT SQEWVFQMLS RQNNYTVNNK RNGVAKVNIF 
       560        570        580        590        600
FKELNYKTNS ESPSVTMVTL LSNLGSQWSL WFGSSVLSVV EMAELVFDLL 
       610        620        630        640        650
VIMFLMLLRR FRSRYWSPGR GGRGAQEVAS TLASSPPSHF CPHPMSLSLS 
       660        670        680        690 
QPGPAPSPAL TAPPPAYATL GPRPSPGGSA GASSSTCPLG GP 

<p>Reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.</p><p><a href='../manual/sequence_caution' target='_top'>More...</a></p>Sequence cautionⁱ

Natural variant

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	61 – 61	1	F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.34 "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. , 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. Corresponds to variant rs61758859 [ dbSNP | Ensembl ].		VAR_060793
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	114 – 114	1	V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.34 "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. , 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. Corresponds to variant rs61759861 [ dbSNP | Ensembl ].		VAR_060794
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	181 – 181	1	R → W Functional polymorphism; significant increase of amiloride-sensitive sodium currents. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.33 "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. Ref.34 "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. , 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. Corresponds to variant rs55797039 [ dbSNP | Ensembl ].		VAR_060795
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	327 – 327	1	G → C in PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Ref.32 "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.		VAR_026518
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	334 – 334	1	A → T Functional polymorphism; significant decrease of amiloride-sensitive sodium currents. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.26 "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. Ref.34 "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. , 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. Corresponds to variant rs11542844 [ dbSNP | Ensembl ].		VAR_060796
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	402 – 402	1	P → H. Corresponds to variant rs13306616 [ dbSNP | Ensembl ].		VAR_052035
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	493 – 493	1	W → 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 incresed risk for ischemic cerebrovascular events. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.29 "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. Ref.34 "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. , 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. Corresponds to variant rs5742912 [ dbSNP | Ensembl ].		VAR_015833
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	562 – 562	1	S → L in PHA1B. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.29 "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. Corresponds to variant rs137852635 [ dbSNP | Ensembl ].		VAR_015834
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	573 – 573	1	V → I. Corresponds to variant rs59142484 [ dbSNP | Ensembl ].		VAR_060797
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	618 – 618	1	C → F.1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.26 "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. Corresponds to variant rs3741913 [ dbSNP | Ensembl ].		VAR_022142
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	663 – 663	1	T → A.7 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Ref.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. Ref.26 "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. Ref.28 "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. Ref.30 "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. Ref.31 "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. Ref.34 "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. , 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. Corresponds to variant rs2228576 [ dbSNP | Ensembl ].		VAR_015835

Alternative sequence

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>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><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	1 – 1	1	M → MGMARGSLTRVPGVMGEGTQ GPELSLDPDPCSPQSTPGLM KGNKLEEQDPRPLQPIPGLM in isoform 2. Curated		VSP_007719
<p>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><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	1 – 1	1	M → MSSIKGNKLEEQDPRPLQPI PGLM in isoform 6. 1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.6 "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).		VSP_043667
<p>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><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	229 – 245	17	CNQNK…YSSGV → ELLSLPPPDVWKLLYFG in isoform 3. Curated		VSP_007720	Add BLAST
<p>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><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	246 – 669	424	Missing in isoform 3. Curated		VSP_007721	Add BLAST
<p>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><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	327 – 345	19	Missing in isoform 4. Curated		VSP_007722	Add BLAST
<p>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><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	454 – 454	1	G → GQVRSLTPVIPALWEAEAGG SRG in isoform 5. Curated		VSP_007723

Sequence databases

Genome annotation databases

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Coding sequence diversityⁱ

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

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>Provides general information on the entry.</p><p><a href='../manual/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

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

<p>UniProtKB Keywords constitute a <a target="_top" href="/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>Keywords - Technical termⁱ

Documents

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

<p>Provides links to the UniProt Reference Clusters (<a href="/help/uniref">UniRef</a>). UniRef consists of clusters for UniProtKB sequences (including isoforms) and selected UniParc sequences, in order to obtain complete coverage of the sequence space at resolutions of 100%, 90% and 50% identity.</p><p><a href='../manual/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ