WDR59
Description
The WDR59 (WD repeat domain 59) is a protein-coding gene located on chromosome 16.
WDR59 is a protein that plays a role in the regulation of the mTORC1 signaling pathway, which is involved in cell growth and metabolism. It is part of the GATOR2 complex, which acts as an activator of the amino acid-sensing branch of the mTORC1 pathway. The GATOR2 complex works by inhibiting the activity of another complex called GATOR1. GATOR2 likely functions as an E3 ubiquitin-protein ligase, which means it can add a small protein tag called ubiquitin to other proteins. This tagging process can lead to the degradation of the tagged protein. In the case of GATOR2, it tags the NPRL2 protein, which is a component of the GATOR1 complex. This tagging leads to the inactivation of GATOR1. GATOR2 is regulated by the availability of amino acids. When there are plenty of amino acids, GATOR2 is active and inhibits GATOR1. However, when amino acids are scarce, GATOR2 is inhibited, allowing GATOR1 to become active. WDR59 also interacts with other proteins, including CASTOR1, CASTOR2, SESN1, SESN2, SESN3, and DDB1-CUL4A/B E3 ligase complexes.
WDR59, as part of the GATOR2 complex, activates the mTORC1 pathway's amino acid-sensing branch, indirectly by inhibiting the GATOR1 subcomplex. GATOR2 likely functions as an E3 ubiquitin-protein ligase towards GATOR1. In the presence of ample amino acids, GATOR2 ubiquitinates the NPRL2 component of GATOR1, leading to its inactivation. When amino acids are scarce, GATOR2 is inhibited, allowing activation of the GATOR1 complex.
WDR59 is also known as CDW12, FP977, p90-120.
Associated Diseases
- primary familial polycythemia due to EPO receptor mutation
- hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
- alpha thalassemia-intellectual disability syndrome type 1
- alpha-thalassemia-myelodysplastic syndrome
- hemoglobin D disease
- hemoglobin E-beta-thalassemia syndrome
- delta-beta-thalassemia
- hemolytic anemia due to diphosphoglycerate mutase deficiency
- Heinz body anemia
- hemoglobin C-beta-thalassemia syndrome
- dominant beta-thalassemia
- hemolytic anemia due to adenylate kinase deficiency
- erythrocytosis, familial, 3
- erythrocytosis, familial, 6
- X-linked sideroblastic anemia 1
