Piezo-type mechanosensitive ion channel component 1 (PIEZO1)
The protein contains 2521 amino acids for an estimated molecular weight of 286790 Da.
Pore-forming subunit of a mechanosensitive non-specific cation channel (PubMed:23479567, PubMed:23695678). Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling (PubMed:20016066). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (PubMed:25119035). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (By similarity). Acts as sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells. In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation. (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
No binding partner found
Biological Process
Cation transport
Cellular response to mechanical stimulus
Detection of mechanical stimulus
Positive regulation of cell-cell adhesion mediated by integrin
Positive regulation of integrin activation
Positive regulation of myotube differentiation
Regulation of membrane potential
The reference OMIM entry for this protein is 194380
Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; dhs
Dehydrated hereditary stomatocytosis
Xerocytosis, hereditary
Desiccytosis, hereditary
Pseudohyperkalemia, familial, 1, due to red cell leak; p
A number sign (#) is used with this entry because of evidence that dehydrated hereditary stomatocytosis (DHS) is caused by heterozygous mutation in the PIEZO1 gene (611184) on chromosome 16q24.
DESCRIPTION
Hereditary xerocytosis, also known as dehydrated hereditary stomatocytosis (DHS), is an autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. DHS erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. DHS patients typically exhibit mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration (summary by Zarychanski et al., 2012). Patients may also show perinatal edema and pseudohyperkalemia due to loss of K+ from red cells stored at room temperature. A minor proportion of red cells appear as stomatocytes on blood films. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The course of DHS is frequently associated with iron overload, which may lead to hepatosiderosis (summary by Albuisson et al., 2013). The 'leaky red blood cells' in familial pseudohyperkalemia show a temperature-dependent loss of potassium when stored at room temperature, manifesting as apparent hyperkalemia. The red blood cells show a reduced life span in vivo, but there is no frank hemolysis. Studies of cation content and transport show a marginal increase in permeability at 37 degrees C and a degree of cellular dehydration, qualitatively similar to the changes seen in dehydrated hereditary stomatocytosis. Physiologic studies show that the passive leak of potassium has an abnormal temperature dependence, such that the leak is less sensitive to temperature than that in normal cells (summary by Iolascon et al., 1999). - Genetic Heterogeneity of Hereditary Stomatocytosis Another form of stomatocytosis involving familial pseudohyperkalemia has been mapped to chromosome 2q35 (609153). There is also an overhydrated form of hereditary stomatocytosis (OHS; see 185000).CLINICAL FEATURES
Miller et al. (1971) described a large kindred of Swiss-German origin with stomatocytosis, in which 3 affected sibs appeared to be homozygous whereas 50 other affected family members were heterozygous. The homozygotes had hemolytic anemia, decreased osmotic fragility, increased intracellular sodium, and marked increase in sodium pump rates. The heterozygotes had no anemia but had cholelithiasis and intermittent jaundice. Decreased fragility distinguished it from other forms of stomatocytosis with hemolytic anemia. Glader et al. (1974) described the disorder as desiccytosis. In 16 members of 3 generations of a kindred from Edinburgh, Stewart et al. (1979) observed elevated plasma potassium if the red cells were not separated promptly. In vivo plasma potassium concentrations were normal. Affected persons were not anemic. The authors postulated that digoxin, which inhibits the red cell sodium-potassium pump, could exacerbate red cell potassium depletion and lead to frank hemolysis. In the presence of impaired renal or adrenal function, dangerous hyperkalemia might result. Luciani et al. (1980) reported an affected mother and daughter. The family reported by Stewart and Ellory (1985) showed mild hereditary xerocy ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 194380 was added.