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";
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.
Pfam Domains: PF01857 - Retinoblastoma-associated protein B domain PF01858 - Retinoblastoma-associated protein A domain PF08934 - Rb C-terminal domain PF11934 - Domain of unknown function (DUF3452)
ModBase Predicted Comparative 3D Structure on P06400
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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.
AK291258 - Homo sapiens cDNA FLJ75028 complete cds, highly similar to Homo sapiens retinoblastoma 1 (including osteosarcoma) (RB1), mRNA. AK300284 - Homo sapiens cDNA FLJ51085 complete cds, highly similar to Retinoblastoma-associated protein. AK307730 - Homo sapiens cDNA, FLJ97678. AK299179 - Homo sapiens cDNA FLJ52431 complete cds, highly similar to Retinoblastoma-associated protein. BC040540 - Homo sapiens retinoblastoma 1, mRNA (cDNA clone MGC:39656 IMAGE:5267622), complete cds. BC039060 - Homo sapiens retinoblastoma 1, mRNA (cDNA clone MGC:29887 IMAGE:5142020), complete cds. M19701 - Human mutated retinoblastoma susceptibility (RB) mRNA, complete cds. M28419 - Human retinoblastoma susceptibility protein mRNA, complete cds. M15400 - Human retinoblastoma susceptibility mRNA, complete cds. L41870 - Homo sapiens retinoblastoma susceptibility protein (RB1) mRNA and mutations. AB208788 - Homo sapiens mRNA for Retinoblastoma-associated protein variant protein. M33647 - Human retinoblastoma associated (RB1) mRNA, complete cds. CU691646 - Synthetic construct Homo sapiens gateway clone IMAGE:100017847 5' read RB1 mRNA. AB384726 - Synthetic construct DNA, clone: pF1KB3021, Homo sapiens RB1 gene for retinoblastoma-associated protein, complete cds, without stop codon, in Flexi system. DQ891564 - Synthetic construct clone IMAGE:100004194; FLH178103.01X; RZPDo839H07126D retinoblastoma 1 (including osteosarcoma) (RB1) gene, encodes complete protein. DQ894752 - Synthetic construct Homo sapiens clone IMAGE:100009212; FLH178099.01L; RZPDo839H07125D retinoblastoma 1 (including osteosarcoma) (RB1) gene, encodes complete protein. KJ897452 - Synthetic construct Homo sapiens clone ccsbBroadEn_06846 RB1 gene, encodes complete protein. AF043224 - Homo sapiens retinoblastoma susceptibility protein (RB1) mRNA, partial cds. AY429568 - Homo sapiens RB1v_1 mRNA sequence; alternatively spliced. LP986369 - Sequence 7 from Patent EP3201339. MA014029 - JP 2017536338-A/7: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT. AK307125 - Homo sapiens cDNA, FLJ97073. LP986371 - Sequence 9 from Patent EP3201339. MA014031 - JP 2017536338-A/9: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT. JD504691 - Sequence 485715 from Patent EP1572962. JD526683 - Sequence 507707 from Patent EP1572962. JD503614 - Sequence 484638 from Patent EP1572962. JD260576 - Sequence 241600 from Patent EP1572962. FW573293 - JP 2010529847-A/14: Oligonucleotides for modulation of target RNA activity. JD258017 - Sequence 239041 from Patent EP1572962. JD184660 - Sequence 165684 from Patent EP1572962. JD317737 - Sequence 298761 from Patent EP1572962. JD043853 - Sequence 24877 from Patent EP1572962. JD482139 - Sequence 463163 from Patent EP1572962. JD433041 - Sequence 414065 from Patent EP1572962. JD324886 - Sequence 305910 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_cellcyclePathway - Cyclins and Cell Cycle Regulation h_p27Pathway - Regulation of p27 Phosphorylation during Cell Cycle Progression h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition h_g1Pathway - Cell Cycle: G1/S Check Point h_hcmvPathway - Human Cytomegalovirus and Map Kinase Pathways h_tercPathway - Overview of telomerase RNA component gene hTerc Transcriptional Regulation h_fbw7Pathway - Cyclin E Destruction Pathway h_p53Pathway - p53 Signaling Pathway h_pmlPathway - Regulation of transcriptional activity by PML h_telPathway - Telomeres, Telomerase, Cellular Aging, and Immortality h_arfPathway - Tumor Suppressor Arf Inhibits Ribosomal Biogenesis h_fasPathway - FAS signaling pathway ( CD95 ) h_rbPathway - RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage h_skp2e2fPathway - E2F1 Destruction Pathway h_tnfr1Pathway - TNFR1 Signaling Pathway h_btg2Pathway - BTG family proteins and cell cycle regulation h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) h_tidPathway - Chaperones modulate interferon Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P06400 (Reactome details) participates in the following event(s):
R-HSA-69227 Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes R-HSA-188386 Association of Rb with Cyclin E:Cdk2 complexes R-HSA-2172666 RB1 binds condensin II R-HSA-8985460 RUNX2 binds RB1 R-NUL-8985474 Runx2 binds RB1 R-HSA-9018017 RB1 binds and inhibits E2F1/2/3:DP1/2 complexes R-HSA-113503 PP2A mediated localization of RB1 protein in chromatin R-HSA-113643 Replication initiation regulation by Rb1/E2F1 R-HSA-188390 Cyclin E:Cdk2-mediated phosphorylation of Rb R-HSA-8985485 RUNX2 and RB1 bind the BGLAP gene promoter R-HSA-8985627 RUNX2 and RB1 bind the COL1A1 gene promoter R-NUL-8985490 Runx2:RB1 binds the BGLAP gene promoter R-HSA-187948 Phosphorylation of proteins involved in the G1/S transition by Cyclin A:Cdk2 R-HSA-69231 Cyclin D associated events in G1 R-HSA-69202 Cyclin E associated events during G1/S transition R-HSA-2299718 Condensation of Prophase Chromosomes R-HSA-8940973 RUNX2 regulates osteoblast differentiation R-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1 R-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes R-HSA-69236 G1 Phase R-HSA-69206 G1/S Transition R-HSA-68875 Mitotic Prophase R-HSA-8941326 RUNX2 regulates bone development R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-113510 E2F mediated regulation of DNA replication R-HSA-453279 Mitotic G1-G1/S phases R-HSA-68886 M Phase R-HSA-8878166 Transcriptional regulation by RUNX2 R-HSA-69242 S Phase R-HSA-69278 Cell Cycle (Mitotic) R-HSA-212436 Generic Transcription Pathway R-HSA-1640170 Cell Cycle R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
