Catalytic activity:Protein tyrosine phosphate + H (2) O = protein tyrosine + phosphate. ,Disease:Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor. ,Disease:Defects in PTPN11 are a cause of Noonan-like syndrome [MIM:163955]; also known as Noonan-like/multiple giant cell lesion syndrome. It is an autosomal dominant disorder characterized by Noonan features associates with giant cell lesions of bone and soft tissue. ,Disease:Defects in PTPN11 are the cause of LEOPARD syndrome [MIM:151100]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines , electrocardiographic conduction abnormalities , ocular hypertelorism , pulmonic stenosis , abnormalities of genitalia , retardation of growth , and deafness. ,Disease:Defects in PTPN11 are the cause of Noonan syndrome 1 (NS1) [MIM:163950]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features , short stature , hypertelorism , cardiac anomalies , deafness , motor delay , and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome , with an estimated incidence of 1 in 1000-2500 live births. Mutations in PTPN11 account for more than 50% of the cases. Rarely , NS is associated with juvenile myelomonocytic leukemia (JMML) . NS1 inheritance is autosomal dominant. ,Domain:The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition , possibly by inducing a conformational change in the enzyme. ,Function:Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. ,PTM:Phosphorylated on Tyr-546 and Tyr-584 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. ,similarity:Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily. ,similarity:Contains 1 tyrosine-protein phosphatase domain. ,similarity:Contains 2 SH2 domains. ,subunit:Interacts with phosphorylated LIME1 and BCAR3. Interacts with SHB and INPP5D/SHIP1 (By similarity) . Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and MPZL1. Interacts with FCRL3 , FCRL4 , FCRL6 and ANKHD1. ,tissue specificity:Widely expressed , with highest levels in heart , brain , and skeletal muscle. ,
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