RB1 (retinoblastoma)

Identity

Other names	human retinoblastoma suspectibility gene
Hugo	RB1
Location	13q14

DNA/RNA

	c-RB1 at 13q14 in normal cells: PAC 825K22 (top) and PAC 971H14 (bottom) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi
Description	27 exons spanning 180 kb
Transcription	4.7 kb mRNA, 2.7 kb open reading frame, 2 kb 3´-UTR

Protein

Description	928aa nuclear phosphoprotein; 110 kDa; pRB is phosphorylated by members of the cyclin-dependent kinase (cdk) system prior to the entry into S-phase; hypophosphorylated pRB binds to members of the E2F family of transcription factors; binding to E2F is mediated by by two domains within pRB (pocket domains)
Expression	ubiquitous
Localisation	nucleus
Function	cell cycle regulation, differentiation
Homology	pRB, p107, and p130 constitute a small family of nuclear proteins with significant sequence similarity in two discontinuous areas (pockets domains); conditional on the phosphorylation status, these pocket proteins can bind transforming proteins of DNA tumor viruses as well as nuclear proteins

Mutations

Germinal

germline mutations in the RB1 gene are causative for hereditary predisposition to retinoblastoma; the spectrum of predisposing mutations includes large deletions (about 20%), single base substitutions (about 50%) and small length mutations (about 30%); most mutations are associated with almost complete penetrance: some rare alleles show incomplete penetrace and reduced expressivity (low penetrance retinoblastoma)

Somatic

in retinoblastomas, both RB1 alleles are mutated; in addtion to the mutational spectrum of germinal mutations, retinoblastomas can show loss of heterozygosity and hypermethylation at the CpG-island associated with the 5Œ-end of the RB1 gene

Implicated in

Entity	Retinoblastoma
Disease	hereditary predisposition to retinoblastoma formation in carrieres of a germinal mutation somatic inactivation of both RB1 alleles can result in sporadic unilateral retinobalstoma
Entity	Sarcomas
Disease	carriers of a germinal RB1gene mutation are predisposed to soft tissue sarcomas and osteogenic sarcomas somatic inactivation of both RB1 alleles observed in some sarcomas
Entity	various cancers
Disease	RB1 gene mutations have been observed in several tumor entities. In lung cancer there is a notable high frequency of RB1 gene mutations although no increased incidence of these tumors has been observed in carriers of a germinal RB1 gene mutation.

External links

	Nomenclature
Hugo	RB1
GDB	RB1
Entrez_Gene	RB1  5925  retinoblastoma 1 (including osteosarcoma)
	Cards
Atlas	RB1ID90
GeneCards	RB1
Ensembl	RB1 [Search_View]   ENSG00000139687 [Gene_View]
Genatlas	RB1
GeneLynx	RB1
eGenome	RB1
euGene	5925
	Genomic and cartography
GoldenPath	RB1  -  13q14   chr13:47775884-47954025 +  13q14.2   [Description]    (hg18-Mar_2006)
Ensembl	RB1 - 13q14.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	RB1
	Gene and transcription
Genbank	AB208788 [ ENTREZ ]
Genbank	AF043224 [ ENTREZ ]
Genbank	AK291258 [ ENTREZ ]
Genbank	AK307125 [ ENTREZ ]
Genbank	AK307730 [ ENTREZ ]
RefSeq	NM_000321 [ SRS ]    NM_000321 [ ENTREZ ]
RefSeq	AC_000056 [ SRS ]    AC_000056 [ ENTREZ ]
RefSeq	AC_000145 [ SRS ]    AC_000145 [ ENTREZ ]
RefSeq	NC_000013 [ SRS ]    NC_000013 [ ENTREZ ]
RefSeq	NT_024524 [ SRS ]    NT_024524 [ ENTREZ ]
RefSeq	NW_001838074 [ SRS ]    NW_001838074 [ ENTREZ ]
RefSeq	NW_925473 [ SRS ]    NW_925473 [ ENTREZ ]
AceView	RB1 AceView - NCBI
Unigene	Hs.408528 [ SRS ]    Hs.408528 [ NCBI ]     HS408528 [ spliceNest ]
Fast-db	5211 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P06400 [ SRS]    P06400 [ EXPASY ]     P06400 [ INTERPRO ]
Interpro	IPR006670 Cyclin [ SRS ]    IPR006670 Cyclin [ EBI ]
Interpro	IPR013763 Cyclin_related [ SRS ]    IPR013763 Cyclin_related [ EBI ]
Interpro	IPR002720 RB_A [ SRS ]    IPR002720 RB_A [ EBI ]
Interpro	IPR015652 Rb_associated [ SRS ]    IPR015652 Rb_associated [ EBI ]
Interpro	IPR002719 RB_B [ SRS ]    IPR002719 RB_B [ EBI ]
Interpro	IPR015030 Rb_C [ SRS ]    IPR015030 Rb_C [ EBI ]
CluSTr	P06400
Pfam	PF01858 RB_A [ SRS ]    PF01858 RB_A [ Sanger ]    pfam01858 [ NCBI-CDD ]
Pfam	PF01857 RB_B [ SRS ]    PF01857 RB_B [ Sanger ]    pfam01857 [ NCBI-CDD ]
Pfam	PF08934 Rb_C [ SRS ]    PF08934 Rb_C [ Sanger ]    pfam08934 [ NCBI-CDD ]
Smart	SM00385 CYCLIN [EMBL]
Blocks	P06400
PDB	RB1 [ SRS ]    RB1 [ PdbSum ],   RB1 [ IMB ]   RB1 [ RSDB ]
HPRD	01574
	Protein Interaction databases
DIP	P06400
IntAct	P06400
	Polymorphism : SNP, mutations, diseases
OMIM	109800;180200;259500    [ map ]
GENECLINICS	109800;180200;259500
SNP	RB1 [dbSNP-NCBI]
SNP	NM_000321 [SNP-NCI]
SNP	RB1 [GeneSNPs - Utah]  RB1] [HGBASE - SRS]
HAPMAP	RB1 [HAPMAP]
COSMIC	RB1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	RB1
	General knowledge
Family Browser	RB1 [UCSC Family Browser]
SOURCE	NM_000321
SMD	Hs.408528
SAGE	Hs.408528
GO	cell cycle checkpoint [Amigo]  cell cycle checkpoint
GO	G1/S transition of mitotic cell cycle [Amigo]  G1/S transition of mitotic cell cycle
GO	negative regulation of transcription from RNA polymerase II promoter [Amigo]  negative regulation of transcription from RNA polymerase II promoter
GO	M phase [Amigo]  M phase
GO	chromatin [Amigo]  chromatin
GO	molecular_function [Amigo]  molecular_function
GO	transcription factor activity [Amigo]  transcription factor activity
GO	transcription coactivator activity [Amigo]  transcription coactivator activity
GO	nucleus [Amigo]  nucleus
GO	nucleus [Amigo]  nucleus
GO	nucleoplasm [Amigo]  nucleoplasm
GO	transcription factor complex [Amigo]  transcription factor complex
GO	spindle [Amigo]  spindle
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	negative regulation of protein kinase activity [Amigo]  negative regulation of protein kinase activity
GO	cell cycle arrest [Amigo]  cell cycle arrest
GO	transcription factor binding [Amigo]  transcription factor binding
GO	negative regulation of cell proliferation [Amigo]  negative regulation of cell proliferation
GO	transcription repressor activity [Amigo]  transcription repressor activity
GO	chromatin modification [Amigo]  chromatin modification
GO	PML body [Amigo]  PML body
GO	kinase binding [Amigo]  kinase binding
GO	negative regulation of cell growth [Amigo]  negative regulation of cell growth
GO	androgen receptor signaling pathway [Amigo]  androgen receptor signaling pathway
GO	enucleate erythrocyte differentiation [Amigo]  enucleate erythrocyte differentiation
GO	regulation of lipid kinase activity [Amigo]  regulation of lipid kinase activity
GO	interspecies interaction between organisms [Amigo]  interspecies interaction between organisms
GO	positive regulation of macrophage differentiation [Amigo]  positive regulation of macrophage differentiation
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	positive regulation of transcription from RNA polymerase II promoter [Amigo]  positive regulation of transcription from RNA polymerase II promoter
GO	androgen receptor binding [Amigo]  androgen receptor binding
GO	striated muscle cell differentiation [Amigo]  striated muscle cell differentiation
GO	cell division [Amigo]  cell division
GO	G1 phase [Amigo]  G1 phase
BIOCARTA	HIV-I Nef: negative effector of Fas and TNF    [Genes]
BIOCARTA	Influence of Ras and Rho proteins on G1 to S Transition    [Genes]
BIOCARTA	Tumor Suppressor Arf Inhibits Ribosomal Biogenesis    [Genes]
BIOCARTA	BTG family proteins and cell cycle regulation    [Genes]
BIOCARTA	Cyclins and Cell Cycle Regulation    [Genes]
BIOCARTA	FAS signaling pathway ( CD95 )    [Genes]
BIOCARTA	Cyclin E Destruction Pathway    [Genes]
BIOCARTA	Cell Cycle: G1/S Check Point    [Genes]
BIOCARTA	Human Cytomegalovirus and Map Kinase Pathways    [Genes]
BIOCARTA	Regulation of p27 Phosphorylation during Cell Cycle Progression    [Genes]
BIOCARTA	p53 Signaling Pathway    [Genes]
BIOCARTA	Regulation of transcriptional activity by PML    [Genes]
BIOCARTA	Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)    [Genes]
BIOCARTA	RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage    [Genes]
BIOCARTA	E2F1 Destruction Pathway    [Genes]
BIOCARTA	Telomeres, Telomerase, Cellular Aging, and Immortality    [Genes]
BIOCARTA	Overview of telomerase RNA component gene hTerc Transcriptional Regulation    [Genes]
BIOCARTA	Chaperones modulate interferon Signaling Pathway    [Genes]
BIOCARTA	TNFR1 Signaling Pathway    [Genes]
KEGG	Cell cycle
PubGene	RB1
TreeFam	RB1
CTD	5925 [Comparative ToxicoGenomics Database]
	Other databases
Other database	RB1-gene mutation database
	Probes
Probe	RB1 at 1q23 in normal cells (Bari)
Probe	RB1 Related clones (RZPD - Berlin)
	PubMed
PubMed	472 Pubmed reference(s) in LocusLink

Bibliography

Genomic organization of the human retinoblastoma gene.

T'Ang A, Wu KJ, Hashimoto T, Liu WY, Takahashi R, Shi XH, Mihara K, Zhang FH, Chen YY, Du C

Oncogene. 1989 ; 4 (4) : 401-407.

PMID 2717184

The retinoblastoma protein is phosphorylated on multiple sites by human cdc2.

Lees JA, Buchkovich KJ, Marshak DR, Anderson CW, Harlow E

The EMBO journal. 1991 ; 10 (13) : 4279-4290.

PMID 1756735

The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F.

Hiebert SW, Chellappan SP, Horowitz JM, Nevins JR

Genes & development. 1992 ; 6 (2) : 177-185.

PMID 1531329

Complete genomic sequence of the human retinoblastoma susceptibility gene.

Toguchida J, McGee TL, Paterson JC, Eagle JR, Tucker S, Yandell DW, Dryja TP

Genomics. 1993 ; 17 (3) : 535-543.

PMID 7902321

The retinoblastoma protein and cell cycle control.

Weinberg RA

Cell. 1995 ; 81 (3) : 323-330.

PMID 7736585

RB kinases and RB-binding proteins: new points of view.

Taya Y

Trends in biochemical sciences. 1997 ; 22 (1) : 14-17.

PMID 9020586

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	09-1999	Dietmar R Lohmann
		Institut fuer Humangenetik, Hufelandstr. 55, D-45122 Essen, Germany

Citation

This paper should be referenced as such :

Lohmann DR . RB1 (retinoblastoma). Atlas Genet Cytogenet Oncol Haematol. September 1999 . URL : http://AtlasGeneticsOncology.org/Genes/RB1ID90.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 17:49:25 2008