Human Gene RB1 (uc001vcb.1) Description and Page Index
Description: retinoblastoma 1 RefSeq Summary (NM_000321): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: BC040540.1, SRR1660809.155247.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END## Transcript (Including UTRs) Position: hg18 chr13:47,775,884-47,954,027 Size: 178,144 Total Exon Count: 27 Strand: + Coding Region Position: hg18 chr13:47,776,050-47,952,208 Size: 176,159 Coding Exon Count: 27
ID:RB_HUMAN DESCRIPTION: RecName: Full=Retinoblastoma-associated protein; AltName: Full=p105-Rb; AltName: Full=pRb; Short=Rb; AltName: Full=pp110; 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. SUBUNIT: Interacts with ATAD5. Interacts with PRMT2, CDK1 and CDK2 (By similarity). The hypophosphorylated form interacts with and sequesters the E2F1 transcription factor. Interacts with heterodimeric E2F/DP transcription factor complexes containing TFDP1 and either E2F1, E2F3, E2F4 or E2F5, or TFDP2 and E2F4. The unphosphorylated form interacts with EID1, ARID3B, KDM5A, SUV39H1, MJD2A/JHDM3A and THOC1. Interacts with the N-terminal domain of TAF1. Interacts with AATF, DNMT1, LIN9, LMNA, SUV420H1, SUV420H2, PELP1, UHRF2 and TMPO-alpha. May interact with NDC80. Interacts with GRIP1 and UBR4. Interacts with ARID4A and KDM5B. Interacts with E4F1 and LIMD1. Interacts with SMARCA4/BRG1 AND HDAC1 (By similarity). Interacts with adenovirus E1A protein, HPV E7 protein and SV40 large T antigen. Interacts with PSMA3 and USP4. Interacts (when methylated at Lys-860) with L3MBTL1. Interacts with CHEK2; phosphorylates RB1. Interacts with human cytomegalovirus/HHV-5 protein UL123. INTERACTION: P03070:- (xeno); NbExp=2; IntAct=EBI-491274, EBI-617698; P24941:CDK2; NbExp=3; IntAct=EBI-491274, EBI-375096; P30285:Cdk4 (xeno); NbExp=2; IntAct=EBI-491274, EBI-847225; Q155P7:Cenpf (xeno); NbExp=4; IntAct=EBI-491274, EBI-2211248; Q13574-2:DGKZ; NbExp=6; IntAct=EBI-491274, EBI-715527; Q01094:E2F1; NbExp=10; IntAct=EBI-491274, EBI-448924; P06465:E7 (xeno); NbExp=2; IntAct=EBI-491274, EBI-963841; P42685:FRK; NbExp=3; IntAct=EBI-491274, EBI-1383583; Q13547:HDAC1; NbExp=2; IntAct=EBI-491274, EBI-301834; P52927:Hmga2 (xeno); NbExp=5; IntAct=EBI-491274, EBI-912574; Q9R002:Ifi202 (xeno); NbExp=5; IntAct=EBI-491274, EBI-3043899; Q14653:IRF3; NbExp=2; IntAct=EBI-491274, EBI-2650369; Q16539:MAPK14; NbExp=3; IntAct=EBI-491274, EBI-73946; Q00987:MDM2; NbExp=3; IntAct=EBI-491274, EBI-389668; Q14686:NCOA6; NbExp=3; IntAct=EBI-491274, EBI-78670; P07197:NEFM; NbExp=2; IntAct=EBI-491274, EBI-1105035; Q9UQ80:PA2G4; NbExp=4; IntAct=EBI-491274, EBI-924893; P62136:PPP1CA; NbExp=2; IntAct=EBI-491274, EBI-357253; P55345:PRMT2; NbExp=3; IntAct=EBI-491274, EBI-78458; Q00577:PURA; NbExp=6; IntAct=EBI-491274, EBI-1045860; P04049:RAF1; NbExp=3; IntAct=EBI-491274, EBI-365996; O75150:RNF40; NbExp=3; IntAct=EBI-491274, EBI-744408; Q923E4:Sirt1 (xeno); NbExp=4; IntAct=EBI-491274, EBI-1802585; Q3TKT4:Smarca4 (xeno); NbExp=4; IntAct=EBI-491274, EBI-1210244; Q96PU4:UHRF2; NbExp=4; IntAct=EBI-491274, EBI-625304; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Expressed in the retina. DOMAIN: The Pocket domain binds to the threonine-phosphorylated domain C, thereby preventing interaction with heterodimeric E2F/DP transcription factor complexes. PTM: Phosphorylated by CDK6 and CDK4, and subsequently by CDK2 at Ser-567 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. Phosphorylation at Thr- 821 and Thr-826 promotes interaction between the C-terminal domain C and the Pocket domain, and thereby inhibits interactions with heterodimeric E2F/DP transcription factor complexes. Dephosphorylated at Ser-795 by calcineruin upon calcium stimulation. CDK3/cyclin-C-mediated phosphorylation at Ser-807 and Ser-811 is required for G0-G1 transition. Phosphorylated by CDK1 and CDK2 upon TGFB1-mediated apoptosis (By similarity). PTM: N-terminus is methylated by METTL11A/NTM1 (By similarity). Monomethylated at Lys-860 by SMYD2, promoting interaction with L3MBTL1. 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 susceptibility to 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. They 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. DISEASE: Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [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.ncbi.nlm.nih.gov/sites/GeneTests/lab/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";
Genetic Association Studies of Complex Diseases and Disorders
breast cancer Berns EM et al. 1995, Association between RB-1 gene alterations and factors of favourable prognosis in human breast cancer without effect on survival., International journal of cancer. Journal international du cancer. 1995 Apr;64(2):140-5.
osteosarcoma Issing WJ et al. 1993, An association of the RB gene with osteosarcoma: molecular genetic evaluation of a case of hereditary retinoblastoma., European archives of oto-rhino-laryngology. 1993 ;250(5):277-80.
retinoblastoma Houdayer, C. et al. 2004, Comprehensive screening for constitutional RB1 mutations by DHPLC and QMPSF., Human mutation. 2004 Feb;23(2):193-202.
This study demonstrates the reliability of DHPLC for RB1 analysis, but also illustrates the need for a deletion scanning approach. Finally, considering the benefits to retinoblastoma patients, RB1 testing should be widely implemented in routine healthcare because our study clearly illustrates its feasibility.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P06400
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.