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Protein: RB_HUMAN

Retinoblastoma-associated protein

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. more...

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.

SUBCELLULAR LOCATION: Nucleus.

TISSUE SPECIFICITY: Expressed in the retina.

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.

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.

DISEASE: Defects in RB1 are a cause of bladder cancer [MIM:109800].

DISEASE: Defects in RB1 are a cause of osteogenic sarcoma [MIM:259500].

SIMILARITY: Belongs to the retinoblastoma protein (RB) family. WEB RESOURCE: Name=RB1base; Note=RB1 mutation db; URL="http://rb1-lsdb.d-lohmann.de/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RB1ID90.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=RB1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/rb1/"; WEB RESOURCE: Name=Wikipedia; Note=Retinoblastoma protein entry; URL="http://en.wikipedia.org/wiki/Retinoblastoma_protein";

COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.