Tchem RB1 Retinoblastoma-associated protein

Protein Summary

Description

Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. 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, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). (Microbial infection) 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. The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P06400
• A8K5E3
• P78499
• Q5VW46
• Q8IZL4

Gene Name

• RB1

Ensembl ID

• ENST00000267163
• ENSP00000267163
• ENSG00000139687

Symbol

• RB
• pRb
• OSRC
• pp110
• p105-Rb
• PPP1R130

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
hub protein	1
kinase	1

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Retinoblastoma-associated Protein

Protein / Nucleic Acid Binding / Retinoblastoma-associated Protein

DTO Classes

Protein / Nucleic Acid Binding / Retinoblastoma-associated Protein

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1741.88   (req: < 5)

Gene RIFs: 828   (req: <= 3)

Antibodies: 3155   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1741.88   (req: >= 5)

Gene RIFs: 828   (req: > 3)

Antibodies: 3155   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 66

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0