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Details on Person UniProt:P06400 RB1
| Class:Id | ReferenceGeneProduct:62886 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-928 added on Fri February 6 2015;initiator methionine:1 for 62886 removed on Fri Nov 03 2023;initiator methionine: for 62886 added on Fri Nov 03 2023;initiator methionine: for 62886 removed on Fri Aug 15 2025;initiator methionine:1 for 62886 added on Fri Aug 15 2025 |
| _displayName | UniProt:P06400 RB1 |
| _timestamp | 2025-08-15 21:02:45 |
| chain | initiator methionine:1 chain:2-928 |
| checksum | C8E746111E19CC32 |
| comment | FUNCTION Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802). Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802). Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802). RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261). 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).FUNCTION (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.SUBUNIT The hypophosphorylated form interacts with and sequesters the E2F1 transcription factor, thereby inhibiting E2F1 transcription (PubMed:20940255, PubMed:8336704). Interacts with heterodimeric E2F/DP transcription factor complexes containing TFDP1 and either E2F1, E2F3, E2F4 or E2F5, or TFDP2 and E2F4. Interacts (when hyperphosphorylated and hypophosphorylated) with PKP3; the interaction inhibits RB1 interaction with and repression of the transcription factor E2F1, potentially via sequestering RB1 to the cytoplasm (By similarity). The unphosphorylated form interacts with EID1, ARID3B, KDM5A, SUV39H1, MJD2A/JHDM3A and THOC1. Interacts with the N-terminal domain of TAF1. Interacts with SNW1, ATAD5, AATF, DNMT1, LIN9, LMNA, KMT5B, KMT5C, PELP1, UHRF2 and TMPO-alpha. 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 PSMA3 and USP4. Interacts (when methylated at Lys-860) with L3MBTL1. Interacts with CHEK2; phosphorylates RB1. Interacts with CDK1 and CDK2 (By similarity). Interacts with PRMT2. Interacts with CEBPA (PubMed:15107404). P-TEFB complex interacts with RB1; promotes phosphorylation of RB1 (PubMed:12037672). Interacts with RBBP9; the interaction disrupts RB1 binding to E2F1 (By similarity). Interacts with KAT2B/PCAF and EP300/P300 (By similarity). Interacts with PAX5 (PubMed:10197586). Interacts (phosphorylated and unphosphorylated) with BLCAP (PubMed:26986503). May interact with NDC80.SUBUNIT (Microbial infection) Interacts with adenovirus E1A protein.SUBUNIT (Microbial infection) Interacts with HPV E7 protein.SUBUNIT (Microbial infection) Interacts with SV40 large T antigen.SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HHV-5 proteins UL82 and UL123.SUBUNIT (Microbial infection) Interacts with molluscum contagiosum virus protein MC007.INTERACTION During keratinocyte differentiation, acetylation by KAT2B/PCAF is required for nuclear localization (PubMed:20940255). Localizes to the cytoplasm when hyperphosphorylated (By similarity).TISSUE SPECIFICITY Expressed in the retina. Expressed in foreskin keratinocytes (at protein level) (PubMed:20940255).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.PTM N-terminus is methylated by METTL11A/NTM1 (By similarity). Monomethylation at Lys-810 by SMYD2 enhances phosphorylation at Ser-807 and Ser-811, and promotes cell cycle progression. Monomethylation at Lys-860 by SMYD2 promotes interaction with L3MBTL1.PTM Acetylated during keratinocyte differentiation. Acetylation at Lys-873 and Lys-874 regulates subcellular localization. Can be deacetylated by SIRT1.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the retinoblastoma protein (RB) family.ONLINE INFORMATION RB1 mutation dbONLINE INFORMATION Retinoblastoma protein entry |
| description | recommendedName: Retinoblastoma-associated protein alternativeName: p105-Rb alternativeName: fullName evidence="69"p110-RB1 alternativeName: pRb shortName: Rb alternativeName: pp110 |
| geneName | RB1 |
| identifier | P06400 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Cell cycle Chromatin regulator Cytoplasm Direct protein sequencing Disease variant DNA-binding Host-virus interaction Methylation Nucleus Phosphoprotein Proteomics identification Reference proteome Repressor Transcription Transcription regulation Tumor suppressor |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | RB1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8954605] ENSEMBL:ENSG00000139687 RB1 [Homo sapiens] |
| secondaryIdentifier | RB_HUMAN A8K5E3 P78499 Q5VW46 Q8IZL4 |
| sequenceLength | 928 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:68642] RB1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:69226] p-S795-RB1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:188389] hyperphosphorylated RB1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:2206327] RB1 I703_E737del [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9659792] RB1 N480del [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9659801] RB1 R661W [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9659807] RB1 R661Q [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9659812] RB1 C706F [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9659821] RB1 C706Y [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9660621] RB1 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:69225] O-phospho-L-serine at 795 [ModifiedResidue:187913] phosphorylated residue at unknown position [FragmentDeletionModification:2206325] Deletion of residues 703 to 737 [FragmentDeletionModification:9659790] Deletion of residues 480 to 480 [ReplacedResidue:9659797] L-arginine 661 replaced with L-tryptophan [ReplacedResidue:9659806] L-arginine 661 replaced with L-glutamine [ReplacedResidue:9659815] L-cysteine 706 replaced with L-phenylalanine [ReplacedResidue:9659822] L-cysteine 706 replaced with L-tyrosine [NonsenseMutation:9660625] Nonsense mutation at L-arginine 552 [NonsenseMutation:9660628] Nonsense mutation at L-arginine 455 |
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No pathways have been reviewed or authored by UniProt:P06400 RB1 (62886)
