RB1
entrez
5925
canonical
uniprot
P06400
canonical
ensembl
ENSG00000139687
resolver
ensp
ENSP00000267163
resolver
ensp
ENSP00000496556
resolver
ensp
ENSP00000497193
resolver
ensp
ENSP00000785925
resolver
enst
ENST00000267163
resolver
enst
ENST00000646097
resolver
enst
ENST00000650461
resolver
genesymbol
RB1
resolver
hgnc
HGNC:9884
resolver
uniprot
A0A2R8YFL6
resolver
uniprot
A0A3B3IS71
resolver
uniprot
A8K5E3
resolver
uniprot
P78499
resolver
uniprot
Q5VW46
resolver
uniprot
Q8IZL4
resolver
uniprot_entry
A0A2R8YFL6_HUMAN
resolver
uniprot_entry
A0A3B3IS71_HUMAN
resolver
uniprot_entry
RB_HUMAN
resolver
uniprot_sec
A8K5E3
resolver
uniprot_sec
P78499
resolver
uniprot_sec
Q5VW46
resolver
uniprot_sec
Q8IZL4
resolver
amino_acid_sequence
MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPLVRLEFEETEEPDFTALCQKLKIPDHVRERAWLTWEKVSSVDGVLGGYIQKKKELWGICIFIAAVDLDEMSFTFTELQKNIEISVHKFFNLLKEIDTSTKVDNAMSRLLKKYDVLFALFSKLERTCELIYLTQPSSSISTEINSALVLKVSWITFLLAKGEVLQMEDDLVISFQLMLCVLDYFIKLSPPMLLKEPYKTAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKEHECNIDEVKNVYFKNFIPFMNSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDARLFLDHDKTLQTDSIDSFETQRTPRKSNLDEEVNVIPPHTPVRTVMNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVKDIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDNIFHMSLLACALEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEGNLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNHTAADMYLSPVRSPKKKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYLRLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLKFKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLSPIPHIPRSPYKFPSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFGTSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQKLAEMTSTRTRMQKQKMNDSMDTSNKEEK
uniprot
proteins
disease_involvement
DISEASE: Childhood cancer retinoblastoma (RB) [MIM:180200]: 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. {ECO:0000269|PubMed:10671068, ECO:0000269|PubMed:11524739, ECO:0000269|PubMed:1352883, ECO:0000269|PubMed:2594029, ECO:0000269|PubMed:7704558, ECO:0000269|PubMed:7795591, ECO:0000269|PubMed:7927327, ECO:0000269|PubMed:8118465, ECO:0000269|PubMed:8346255, ECO:0000269|PubMed:8605116, ECO:0000269|PubMed:8776589, ECO:0000269|PubMed:9140452, ECO:0000269|PubMed:9311732, ECO:0000269|PubMed:9973307}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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 that 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. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:P13405, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:15084261}.; 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. {ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:17974914, ECO:0000269|PubMed:18701596, ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:8892909}.
uniprot
proteins
mass_dalton
106159
uniprot
proteins
mutagenesis
MUTAGEN 821; /note="T->A: Abolishes interaction with Pocket domain; when associated with A-826."; /evidence="ECO:0000269|PubMed:16360038"; MUTAGEN 826; /note="T->A: Abolishes interaction with Pocket domain; when associated with A-821."; /evidence="ECO:0000269|PubMed:16360038"; MUTAGEN 860; /note="K->R: Abolishes monomethylation by SMYD2 and subsequent interaction with L3MBTL1."; /evidence="ECO:0000269|PubMed:20870719"; MUTAGEN 870; /note="K->R: Does not affect the ability to be methylated by SMYD2; when associated with 873-R-R-874."; /evidence="ECO:0000269|PubMed:20870719"; MUTAGEN 873..874; /note="KK->R: Does not affect the ability to be methylated by SMYD2; when associated with 873-R-R-874."; /evidence="ECO:0000269|PubMed:20870719, ECO:0000269|PubMed:20940255"; MUTAGEN 873..874; /note="KK->RR: Does not alter Rb localization in cycling cells, but mislocalizes to the cytoplasm during keratinocyte differentiation. Does not affect the ability to arrest cell growth. Probable loss of acetylation by PCAF."; /evidence="ECO:0000269|PubMed:20870719, ECO:0000269|PubMed:20940255
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:8114739}.; 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. {ECO:0000250, ECO:0000269|PubMed:15084261, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:16360038, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:1756735, ECO:0000269|PubMed:20870719, ECO:0000269|PubMed:22787429}.; PTM: Acetylated during keratinocyte differentiation. Acetylation at Lys-873 and Lys-874 regulates subcellular localization. Can be deacetylated by SIRT1. {ECO:0000269|PubMed:20940255}.
uniprot
proteins
protein_family
Retinoblastoma protein (RB) family
uniprot
proteins
pubmed
10197586
uniprot
proteins
pubmed
10409732
uniprot
proteins
pubmed
10446990
uniprot
proteins
pubmed
10499802
uniprot
proteins
pubmed
10671068
uniprot
proteins
pubmed
10779342
uniprot
proteins
pubmed
10869426
uniprot
proteins
pubmed
10888886
uniprot
proteins
pubmed
11223246
uniprot
proteins
pubmed
11484059
uniprot
proteins
pubmed
11524739
uniprot
proteins
pubmed
11571652
uniprot
proteins
pubmed
12037672
uniprot
proteins
pubmed
12450794
uniprot
proteins
pubmed
12466551
uniprot
proteins
pubmed
12475961
uniprot
proteins
pubmed
12626766
uniprot
proteins
pubmed
12682072
uniprot
proteins
pubmed
12695505
uniprot
proteins
pubmed
1316611
uniprot
proteins
pubmed
1352398
uniprot
proteins
pubmed
1352883
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057823
uniprot
proteins
pubmed
15084261
uniprot
proteins
pubmed
15107404
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15538385
uniprot
proteins
pubmed
15542589
uniprot
proteins
pubmed
15803180
uniprot
proteins
pubmed
15809340
uniprot
proteins
pubmed
15927959
uniprot
proteins
pubmed
15949438
uniprot
proteins
pubmed
16214886
uniprot
proteins
pubmed
16337594
uniprot
proteins
pubmed
16360038
uniprot
proteins
pubmed
16645588
uniprot
proteins
pubmed
17380128
uniprot
proteins
pubmed
1756735
uniprot
proteins
pubmed
17974914
uniprot
proteins
pubmed
17996702
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18701596
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20870719
uniprot
proteins
pubmed
20940255
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21952639
uniprot
proteins
pubmed
22787429
uniprot
proteins
pubmed
23033978
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2594029
uniprot
proteins
pubmed
26986503
uniprot
proteins
pubmed
2701949
uniprot
proteins
pubmed
2717184
uniprot
proteins
pubmed
2839300
uniprot
proteins
pubmed
3413073
uniprot
proteins
pubmed
3480530
uniprot
proteins
pubmed
3657987
uniprot
proteins
pubmed
3823889
uniprot
proteins
pubmed
7525595
uniprot
proteins
pubmed
7704558
uniprot
proteins
pubmed
7795591
uniprot
proteins
pubmed
7881418
uniprot
proteins
pubmed
7902321
uniprot
proteins
pubmed
7927327
uniprot
proteins
pubmed
7935440
uniprot
proteins
pubmed
8114739
uniprot
proteins
pubmed
8118465
uniprot
proteins
pubmed
8336704
uniprot
proteins
pubmed
8346255
uniprot
proteins
pubmed
8414517
uniprot
proteins
pubmed
8605116
uniprot
proteins
pubmed
8776589
uniprot
proteins
pubmed
8892909
uniprot
proteins
pubmed
9140452
uniprot
proteins
pubmed
9145110
uniprot
proteins
pubmed
9311732
uniprot
proteins
pubmed
9495340
uniprot
proteins
pubmed
9858607
uniprot
proteins
pubmed
9973307
uniprot
proteins
sequence_length
928
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20940255}. Cytoplasm {ECO:0000250|UniProtKB:P13405}. Note=During keratinocyte differentiation, acetylation by KAT2B/PCAF is required for nuclear localization (PubMed:20940255). Localizes to the cytoplasm when hyperphosphorylated (By similarity). {ECO:0000250|UniProtKB:P13405, ECO:0000269|PubMed:20940255}.
uniprot
proteins