Tyrosine-protein phosphatase non-receptor type 11 (PTPN11)
The protein contains 597 amino acids for an estimated molecular weight of 68436 Da.
Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573). Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (PubMed:18559669). Dephosphorylates CDC73 (PubMed:26742426). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity). (updated: June 17, 2020)
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.
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.
(right-click above to access to more options from the contextual menu)
Biological Process
Abortive mitotic cell cycle
Activation of MAPK activity
Atrioventricular canal development
Axon guidance
Bergmann glial cell differentiation
Blood coagulation
Brain development
Cellular response to angiotensin
Cellular response to cytokine stimulus
Cellular response to epidermal growth factor stimulus
Cellular response to hydrogen peroxide
Cellular response to insulin-like growth factor stimulus
Cellular response to mechanical stimulus
Cerebellar cortex formation
Cytokine-mediated signaling pathway
DNA damage checkpoint signaling
Ephrin receptor signaling pathway
Epidermal growth factor receptor signaling pathway
ERBB signaling pathway
Face morphogenesis
Fc-epsilon receptor signaling pathway
Fibroblast growth factor receptor signaling pathway
Genitalia development
Glucose homeostasis
Heart development
Homeostasis of number of cells within a tissue
Hormone metabolic process
Hormone-mediated signaling pathway
Innate immune response
Inner ear development
Insulin receptor signaling pathway
Integrin-mediated signaling pathway
Interferon-gamma-mediated signaling pathway
Interleukin-6-mediated signaling pathway
Intestinal epithelial cell migration
Leukocyte migration
Megakaryocyte development
Microvillus organization
Multicellular organism growth
Multicellular organismal reproductive process
Negative regulation of cell adhesion mediated by integrin
Negative regulation of chondrocyte differentiation
Negative regulation of cortisol secretion
Negative regulation of growth hormone secretion
Negative regulation of insulin secretion
Neurotrophin TRK receptor signaling pathway
Obsolete positive regulation of glucose import in response to insulin stimulus
Organ growth
Peptidyl-tyrosine dephosphorylation
Phosphatidylinositol-mediated signaling
Platelet activation
Platelet formation
Platelet-derived growth factor receptor signaling pathway
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of focal adhesion assembly
Positive regulation of glucose import
Positive regulation of hormone secretion
Positive regulation of insulin receptor signaling pathway
Positive regulation of interferon-beta production
Positive regulation of interleukin-6 production
Positive regulation of mitotic cell cycle
Positive regulation of ossification
Positive regulation of peptidyl-tyrosine phosphorylation
Positive regulation of protein kinase B signaling
Positive regulation of tumor necrosis factor production
Regulation of cell adhesion mediated by integrin
Regulation of interferon-gamma-mediated signaling pathway
Regulation of multicellular organism growth
Regulation of protein export from nucleus
Regulation of protein-containing complex assembly
Regulation of type I interferon-mediated signaling pathway
Smooth muscle cell proliferation
T cell costimulation
Triglyceride metabolic process
Type I interferon signaling pathway
Cellular Component
Cytoplasm
Cytosol
Mitochondrion
Nucleoplasm
Nucleus
Plasma membrane raft
Protein complex
Protein-containing complex
Molecular Function
1-phosphatidylinositol-3-kinase activity
Cadherin binding
Cell adhesion molecule binding
D1 dopamine receptor binding
Insulin receptor binding
Insulin receptor substrate binding
Non-membrane spanning protein tyrosine phosphatase activity
Obsolete SH3/SH2 adaptor activity
Peptide hormone receptor binding
Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Phospholipase binding
Phosphoprotein phosphatase activity
Phosphotyrosine residue binding
Protein domain specific binding
Protein kinase binding
Protein tyrosine kinase binding
Protein tyrosine phosphatase activity
Receptor tyrosine kinase binding
Signaling receptor complex adaptor activity
The reference OMIM entry for this protein is 151100
Leopard syndrome 1; lprd1
Lentiginosis, cardiomyopathic
Multiple lentigines syndrome
A number sign (#) is used with this entry because LEOPARD syndrome-1 (LPRD1) is caused by heterozygous mutation in the PTPN11 gene (176876) on chromosome 12q24.
DESCRIPTION
LEOPARD is an acronym for the manifestations of this syndrome as listed by Gorlin et al. (1969): multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. - Genetic Heterogeneity of LEOPARD Syndrome LEOPARD syndrome is a genetically heterogeneous disorder. See also LEOPARD syndrome-2 (611554), caused by mutation in the RAF1 gene (164760), and LEOPARD syndrome-3 (613707), caused by mutation in the BRAF gene (164757).CLINICAL FEATURES
Walther et al. (1966) found asymptomatic cardiac changes associated with generalized lentigo in a mother and her son and daughter. The electrocardiogram in the son suggested myocardial infarction. The mother was shown by cardiac catheterization to have mild pulmonary stenosis. Similar generalized lentigines were described by Moynahan (1962) in 3 unrelated patients (2 females, 1 male). Growth was stunted. In 1 girl, one ovary was absent and the other hypoplastic. The boy had hypospadias and undescended testes. Endocardial and myocardial fibroelastosis may have been present. Intelligence was normal but behavior childish. Matthews (1968) reported mother and 2 half-sib children with generalized lentigines, electrocardiographic changes and murmurs. A history of male-to-male transmission was recorded. Lentigines were also present in the cardiac syndrome reported by Forney et al. (see mitral regurgitation, conductive deafness, etc.; 157800). Polani and Moynahan (1972) gave a full report of 8 patients and their families. They were impressed with the occurrence of left-sided obstructive cardiomyopathy and none of their patients was deaf. They proposed the designation 'progressive cardiomyopathic lentiginosis' for this disorder. St. John Sutton et al. (1981) reported 11 patients, 10 of them male, with classic hypertrophic obstructive cardiomyopathy and lentiginosis. All were sporadic. Mental retardation, deafness, and gonadal and somatic infantilism were uncommon in this series. The 21-year-old patient of Senn et al. (1984) had severe hypertrophic obstructive cardiomyopathy for which surgery was performed on the left ventricle to relieve severe obstruction. Both parents were unaffected; both were 40 years old at the birth of the patient. Peter and Kemp (1990) described a 19-year-old woman who died as a result of respiratory insufficiency secondary to thoracic deformities which, together with a congenital heart defect, led to pulmonary hypertension. The syndrome of cafe-au-lait spots and pulmonic stenosis, described by Watson (1967), is distinct (193520). Coppin and Temple (1997) provided a review of the condition and added 5 cases, including relatives of one of the cases described by Polani and Moynahan (1972). Coppin and Temple (1997) pointed out the difficulty of differentiating LEOPARD syndrome from Noonan syndrome (163950) given previous reports of lentiginosis without lentigines. Shamsadini et al. (1999) described an 18-year-old Iranian girl with LEOPARD syndrome. Clinical manifestations included lentigines, ocular hypertelorism, mental and growth retardation, deaf mutism, and several patches of hair loss on her scalp. There was no family history of lentiginosis or any other inherited condition. Schra ... More on the omim web site
June 29, 2020: 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 151100 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed