| IED ID | IndEnz0002001227 |
| Enzyme Type ID | protease001227 |
| Protein Name |
Retinoblastoma-associated protein p110-RB1 pRb Rb pp105 |
| Gene Name | Rb1 Rb-1 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MPPKAPRRAAAAEPPPPPPPPPREDDPAQDSGPEELPLARLEFEEIEEPEFIALCQKLKVPDHVRERAWLTWEKVSSVDGILEGYIQKKKELWGICIFIAAVDLDEMPFTFTELQKSIETSVYKFFDLLKEIDTSTKVDNAMSRLLKKYNVLCALYSKLERTCELIYLTQPSSALSTEINSMLVLKISWITFLLAKGEVLQMEDDLVISFQLMLCVVDYFIKFSPPALLREPYKTAAIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKEHECNIDEVKNVYFKNFIPFINSLGIVSSNGLPEVESLSKRYEEVYLKNKDLDARLFLDHDKTLQTDPIDSFETERTPRKNNPDEEANVVTPHTPVRTVMNTIQQLMVILNSASDQPSENLISYFNNCTVNPKENILKRVKDVGHIFKEKFANAVGQGCVDIGVQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDNIFHMSLLACALEVVMATYSRSTLQHLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKVEANLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDGEGPDNLEPACPLSLPLQGNHTAADMYLSPLRSPKKRTSTTRVNSAANTETQAASAFHTQKPLKSTSLALFYKKVYRLAYLRLNTLCARLLSDHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLKFKIIVTAYKDLPHAAQETFKRVLIREEEFDSIIVFYNSVFMQRLKTNILQYASTRPPTLSPIPHIPRSPYKFSSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFGTSEKFQKINQMVCNSDRVLKRSAEGGNPPKPLKKLRFDIEGADEADGSKHLPAESKFQQKLAEMTSTRTRMQKQRMNESKDVSNKEEK |
| Enzyme Length | 921 |
| Uniprot Accession Number | P13405 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:8336704). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes. Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription. 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. RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation (PubMed:15750587). Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation (PubMed:16612004). 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) (PubMed:15750587, PubMed:16612004, PubMed:8336704). {ECO:0000250|UniProtKB:P06400, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:15750587, ECO:0000269|PubMed:16612004, ECO:0000269|PubMed:8336704}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (1); Compositional bias (4); Initiator methionine (1); Modified residue (25); Motif (1); Mutagenesis (7); Region (9); Sequence conflict (1) |
| Keywords | Acetylation;Cell cycle;Chromatin regulator;DNA-binding;Methylation;Nucleus;Phosphoprotein;Reference proteome;Repressor;Transcription;Transcription regulation;Tumor suppressor |
| Interact With | Q155P7; Q80UP3; P17679; Q9R002; P24610; P52946; Q3TKT4; Q61412; P15976 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8336704}. Note=During keratinocyte differentiation, acetylation by KAT2B/PCAF is required for nuclear localization. {ECO:0000250|UniProtKB:P06400}. |
| Modified Residue | MOD_RES 2; /note="N,N-dimethylproline; by NTM1"; /evidence="ECO:0000269|PubMed:20668449"; MOD_RES 31; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 243; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 246; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 350; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 364; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 367; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 561; /note="Phosphoserine; by CDK2"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 601; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 605; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 617; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 773; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 781; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 788; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 800; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 803; /note="N6-methyllysine; by SMYD2"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 804; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 814; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 816; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 819; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 834; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 848; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 853; /note="N6-methyllysine; by SMYD2"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 866; /note="N6-acetyllysine; by PCAF"; /evidence="ECO:0000250|UniProtKB:P06400"; MOD_RES 867; /note="N6-acetyllysine; by PCAF"; /evidence="ECO:0000250|UniProtKB:P06400" |
| Post Translational Modification | PTM: Phosphorylated (PubMed:8336704). Phosphorylated by CDK6 and CDK4, and subsequently by CDK2 at Ser-561 in G1, thereby releasing E2F1 which is then able to activate cell growth. Dephosphorylated at the late M phase. Phosphorylation of threonine residues in domain C 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-788 by calcineruin upon calcium stimulation. CDK3/cyclin-C-mediated phosphorylation at Ser-800 and Ser-804 is required for G0-G1 transition (By similarity). Phosphorylated by CDK1 and CDK2 upon TGFB1-mediated apoptosis (By similarity). {ECO:0000250, ECO:0000269|PubMed:8336704}.; PTM: Monomethylation at Lys-803 by SMYD2 enhances phosphorylation at Ser-800 and Ser-804, and promotes cell cycle progression. Monomethylation at Lys-853 by SMYD2 promotes interaction with L3MBTL1 (By similarity). N-terminus is methylated by METTL11A/NTM1. {ECO:0000250, ECO:0000269|PubMed:20668449}.; PTM: Acetylated in the skin (PubMed:20940255). Acetylation at Lys-866 and Lys-867 regulates subcellular localization during keratinocytes differentiation (By similarity). {ECO:0000250|UniProtKB:P06400, ECO:0000269|PubMed:20940255}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10027415; 10049565; 10072353; 10082561; 10097138; 10322110; 10339596; 10341706; 10380928; 10490828; 10498881; 10498884; 10526130; 10541553; 10630640; 10637512; 10667199; 10686616; 10687094; 10702291; 10783170; 10915795; 11016928; 11034201; 11076674; 11085521; 11114892; 11114893; 11134518; 11146559; 11217851; 11230146; 11246230; 11283859; 11306495; 11306549; 11331592; 11432828; 11549719; 11704831; 11704837; 11726663; 11731416; 11748221; 11777937; 11805327; 11818069; 11893245; 11912166; 11930176; 11937028; 11940667; 12000769; 12020798; 12065245; 12086874; 12093735; 12096340; 12191999; 12200151; 12208517; 12234974; 12360286; 12379853; 12386807; 12415005; 12429933; 12434308; 12466851; 12486224; 12498715; 12502747; 12519773; 12520002; 12529408; 12584165; 12588990; 12607001; 12617834; 12627794; 12670909; 12732721; 12760067; 12761567; 12799438; 12810584; 12829028; 12833141; 12839925; 12839964; 12847100; 12853964; 12861012; 12870848; 12894219; 12941272; 12941628; 12944480; 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9192872; 9214616; 9216621; 9219514; 9307303; 9312132; 9331088; 9372965; 9417859; 9426068; 9464541; 9468140; 9508781; 9511723; 9520320; 9537419; 9548727; 9600738; 9610736; 9620848; 9635405; 9639506; 9671308; 9683181; 9716031; 9751770; 9774968; 9794240; 9819431; 9843483; 9917000; |
| Motif | MOTIF 853..869; /note=Bipartite nuclear localization signal; /evidence=ECO:0000269|PubMed:8336704 |
| Gene Encoded By | |
| Mass | 105,367 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |