Disease:Defects in RB1 are a cause of bladder cancer [MIM:109800]. ,Disease:Defects in RB1 are a cause of osteogenic sarcoma [MIM:259500]. ,Disease:Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:180200]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically , about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ("cat eye") is investigated. ,Function:Key regulator of entry into cell division that acts as a tumor suppressor. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated , active form of RB1 interacts with E2F1 and represses its transcription activity , leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and , in particular , that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1 , SUV420H1 and SUV420H2 , leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. In case of viral infections , interactions with SV40 large T antigen , HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. ,online information:RB1 mutation db ,online information:Retinoblastoma protein entry ,PTM:Phosphorylated in G1 , thereby releasing E2F1 which is then able to activate cell growth. Dephosphorylated at the late M phase. SV40 large T antigen , HPV E7 and adenovirus E1A bind to the underphosphorylated , active form of pRb. ,similarity:Belongs to the retinoblastoma protein (RB) family. ,subunit:Interacts with ATAD5 (By similarity) . The hypophosphorylated form interacts with and sequesters the E2F1 transcription factor. The unphosphorylated form interacts with ARID3B , KDM5A , SUV39H1 , MJD2A/JHDM3A and THOC1. Interacts with the N-terminal domain of TAF1. Interacts with AATF , DNMT1 , LIN9 , LMNA , SUV420H1 , SUV420H2 , PELP1 and TMPO-alpha. May interact with NDC80. Interacts with EID1 and UBR4. Interacts with ARID4A and KDM5B. Interacts with E4F1. Interacts with adenovirus E1A protein , HPV E7 protein and SV40 large T antigen. ,tissue specificity:Expressed in the retina. ,
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