InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RB1

Summary

InnateDB Protein

IDBP-32094.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RB1

Protein Name

retinoblastoma 1

Synonyms

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

Species

Homo sapiens

Ensembl Protein

ENSP00000267163

InnateDB Gene

IDBG-32092 (RB1)

Protein Structure

UniProt Annotation

Function

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, SUV420H1 and SUV420H2, 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). 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. {ECO:0000250, ECO:0000269PubMed:15084261}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:20940255}.

Disease Associations

Childhood cancer retinoblastoma (RB) [MIM:180200]: 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. {ECO:0000269PubMed:10671068, ECO:0000269PubMed:11524739, ECO:0000269PubMed:1352883, ECO:0000269PubMed:2594029, ECO:0000269PubMed:7704558, ECO:0000269PubMed:7795591, ECO:0000269PubMed:7927327, ECO:0000269PubMed:8346255, ECO:0000269PubMed:8605116, ECO:0000269PubMed:8776589, ECO:0000269PubMed:9140452, ECO:0000269PubMed:9311732, ECO:0000269PubMed:9973307}. Note=The disease is caused by mutations affecting the gene represented in this entry.Bladder cancer (BLC) [MIM:109800]: A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in the retina.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 479 experimentally validated interaction(s) in this database.
They are also associated with 38 interaction(s) predicted by orthology.

Experimentally validated
Total	479 [view]
Protein-Protein	427 [view]
Protein-DNA	47 [view]
Protein-RNA	0
DNA-DNA	5 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	38 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001047	core promoter binding
GO:0001102	RNA polymerase II activating transcription factor binding
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003713	transcription coactivator activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0019899	enzyme binding
GO:0019900	kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0042802	identical protein binding
GO:0050681	androgen receptor binding
GO:0051219	phosphoprotein binding

Biological Process

GO:0000075	cell cycle checkpoint
GO:0000082	G1/S transition of mitotic cell cycle
GO:0000083	regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000278	mitotic cell cycle
GO:0006338	chromatin remodeling
GO:0006351	transcription, DNA-templated
GO:0006469	negative regulation of protein kinase activity
GO:0007050	cell cycle arrest
GO:0007070	negative regulation of transcription from RNA polymerase II promoter during mitosis
GO:0007093	mitotic cell cycle checkpoint
GO:0007265	Ras protein signal transduction
GO:0007346	regulation of mitotic cell cycle
GO:0008285	negative regulation of cell proliferation
GO:0016032	viral process
GO:0030182	neuron differentiation
GO:0030521	androgen receptor signaling pathway
GO:0031134	sister chromatid biorientation
GO:0031175	neuron projection development
GO:0034088	maintenance of mitotic sister chromatid cohesion
GO:0034349	glial cell apoptotic process
GO:0035914	skeletal muscle cell differentiation
GO:0042551	neuron maturation
GO:0043353	enucleate erythrocyte differentiation
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043550	regulation of lipid kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045445	myoblast differentiation
GO:0045651	positive regulation of macrophage differentiation
GO:0045786	negative regulation of cell cycle
GO:0045842	positive regulation of mitotic metaphase/anaphase transition
GO:0045879	negative regulation of smoothened signaling pathway
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048565	digestive tract development
GO:0048667	cell morphogenesis involved in neuron differentiation
GO:0050680	negative regulation of epithelial cell proliferation
GO:0051146	striated muscle cell differentiation
GO:0051301	cell division
GO:0051402	neuron apoptotic process
GO:0051726	regulation of cell cycle
GO:0071459	protein localization to chromosome, centromeric region
GO:0071922	regulation of cohesin localization to chromatin
GO:0071930	negative regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0090230	regulation of centromere complex assembly
GO:0097284	hepatocyte apoptotic process
GO:2000134	negative regulation of G1/S transition of mitotic cell cycle

Cellular Component

GO:0000785	chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005819	spindle
GO:0016514	SWI/SNF complex
GO:0016605	PML body
GO:0035189	Rb-E2F complex

Protein Structure and Domains

PDB ID

InterPro

IPR002719 Retinoblastoma-associated protein, B-box
IPR002720 Retinoblastoma-associated protein, A-box
IPR013763 Cyclin-like
IPR015030 Retinoblastoma-associated protein, C-terminal
IPR024599 Retinoblastoma-associated protein, N-terminal

PFAM

PF01857
PF01858
PF08934
PF11934

PRINTS

PIRSF

SMART

SM00385

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P06400