UniProt Accession

 RB_HUMAN; P06400; A8K5E3; P78499; Q5VW46; Q8IZL4 

Genbank Protein ID

 M15400; M28419; M33647; L41870; M27866; M27845; M27846; M27847; M27849; M27850; M27851; L35146; M27852; M27853; M27854; M27855; M27856; M27857; M27858; M27859; M27860; L35147; M27862; M27863; M27864; M27865; L41889; L41890; L41891; L41893; L41894; L41895; L41896; L41897; L41898; L41899; L41997; X16439; AF551763; AK291258; AL136960; AL392048; AL392048; AL136960; CH471075; BC039060; BC040540; L11910 

Genbank Nucleotide ID

 AAA69807.1; AAA69808.1; AAA69806.1; AAB59465.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAA53484.1; AAB59467.1; AAA65735.1; AAA65736.1; AAA65737.1; AAA65738.1; AAA65739.1; AAA65740.1; AAA65741.1; AAB59471.1; AAB59473.1; AAB59482.1; CAA34462.1; AAN64133.1; BAF83947.1; CAH70901.1; CAH70901.1; CAH72243.1; CAH72243.1; EAX08793.1; AAH39060.1; AAH40540.1; AAA53483.1 

Protein Name

 Retinoblastoma-associated protein 

Protein Synonyms/Alias

 p105-Rb; pRb; Rb; pp110 

Gene Name

 RB1 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
63	DFTALCQKLKIPDHV	ubiquitination	[1, 2]
65	TALCQKLKIPDHVRE	ubiquitination	[1]
143	KEIDTSTKVDNAMSR	ubiquitination	[2, 3]
265	NRSARIAKQLENDTR	ubiquitination	[1, 2, 4]
279	RIIEVLCKEHECNID	ubiquitination	[1, 2]
289	ECNIDEVKNVYFKNF	ubiquitination	[1]
319	PEVENLSKRYEEIYL	ubiquitination	[1]
329	EEIYLKNKDLDARLF	ubiquitination	[1]
359	ETQRTPRKSNLDEEV	ubiquitination	[1]
420	ESILKRVKDIGYIFK	ubiquitination	[1]
427	KDIGYIFKEKFAKAV	acetylation	[5]
548	NLTREMIKHLERCEH	acetylation	[5]
640	TSAFQTQKPLKSTSL	acetylation	[5]
640	TSAFQTQKPLKSTSL	ubiquitination	[1, 2]
652	TSLSLFYKKVYRLAY	acetylation	[5]
720	KVKNIDLKFKIIVTA	sumoylation	[6]
791	HIPRSPYKFPSSPLR	ubiquitination	[1]
810	NIYISPLKSPYKISE	methylation	[7]
810	NIYISPLKSPYKISE	ubiquitination	[1, 8, 9]
814	SPLKSPYKISEGLPT	ubiquitination	[1]
844	ESFGTSEKFQKINQM	ubiquitination	[1]
847	GTSEKFQKINQMVCN	ubiquitination	[1, 2]
860	CNSDRVLKRSAEGSN	methylation	[10]
870	AEGSNPPKPLKKLRF	ubiquitination	[1]
873	SNPPKPLKKLRFDIE	acetylation	[11, 12, 13]
873	SNPPKPLKKLRFDIE	methylation	[14]
874	NPPKPLKKLRFDIEG	acetylation	[11, 12, 13, 15]
896	KHLPGESKFQQKLAE	acetylation	[2, 5]
896	KHLPGESKFQQKLAE	ubiquitination	[1]
900	GESKFQQKLAEMTST	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [6] Viral oncoproteins E1A and E7 and cellular LxCxE proteins repress SUMO modification of the retinoblastoma tumor suppressor.
 Ledl A, Schmidt D, Müller S.
 Oncogene. 2005 May 26;24(23):3810-8. [PMID: 15806172]
 [7] Interplay between lysine methylation and Cdk phosphorylation in growth control by the retinoblastoma protein.
 Carr SM, Munro S, Kessler B, Oppermann U, La Thangue NB.
 EMBO J. 2011 Jan 19;30(2):317-27. [PMID: 21119616]
 [8] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [9] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [10] Methylation of the retinoblastoma tumor suppressor by SMYD2.
 Saddic LA, West LE, Aslanian A, Yates JR 3rd, Rubin SM, Gozani O, Sage J.
 J Biol Chem. 2010 Nov 26;285(48):37733-40. [PMID: 20870719]
 [11] Acetylation control of the retinoblastoma tumour-suppressor protein.
 Chan HM, Krstic-Demonacos M, Smith L, Demonacos C, La Thangue NB.
 Nat Cell Biol. 2001 Jul;3(7):667-74. [PMID: 11433299]
 [12] Acetylation regulates the differentiation-specific functions of the retinoblastoma protein.
 Nguyen DX, Baglia LA, Huang SM, Baker CM, McCance DJ.
 EMBO J. 2004 Apr 7;23(7):1609-18. [PMID: 15044952]
 [13] p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation.
 Leduc C, Claverie P, Eymin B, Col E, Khochbin S, Brambilla E, Gazzeri S.
 Oncogene. 2006 Jul 13;25(30):4147-54. [PMID: 16501607]
 [14] Lysine methylation regulates the pRb tumour suppressor protein.
 Munro S, Khaire N, Inche A, Carr S, La Thangue NB.
 Oncogene. 2010 Apr 22;29(16):2357-67. [PMID: 20140018]
 [15] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 

Functional Description

 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. 

Sequence Annotation

 REGION 373 771 Pocket; binds T and E1A.
 REGION 373 579 Domain A.
 REGION 580 639 Spacer.
 REGION 640 771 Domain B.
 REGION 763 928 Interaction with LIMD1.
 REGION 771 928 Domain C; mediates interaction with E4F1.
 MOTIF 870 876 Nuclear localization signal (Probable).
 MOD_RES 2 2 N,N-dimethylproline (By similarity).
 MOD_RES 37 37 Phosphoserine.
 MOD_RES 249 249 Phosphoserine; by CDK1.
 MOD_RES 252 252 Phosphothreonine; by CDK1.
 MOD_RES 356 356 Phosphothreonine.
 MOD_RES 373 373 Phosphothreonine; by CDK1.
 MOD_RES 567 567 Phosphoserine; by CDK2.
 MOD_RES 612 612 Phosphoserine; by CHEK2 and CHEK1.
 MOD_RES 795 795 Phosphoserine (By similarity).
 MOD_RES 807 807 Phosphoserine; by CDK1 and CDK3.
 MOD_RES 810 810 N6-methyllysine; by SMYD2.
 MOD_RES 811 811 Phosphoserine; by CDK1 and CDK3.
 MOD_RES 821 821 Phosphothreonine; by CDK6.
 MOD_RES 823 823 Phosphothreonine.
 MOD_RES 826 826 Phosphothreonine; by CDK4.
 MOD_RES 841 841 Phosphothreonine.
 MOD_RES 860 860 N6-methyllysine; by SMYD2.
 MOD_RES 873 873 N6-acetyllysine; by PCAF.
 MOD_RES 874 874 N6-acetyllysine; by PCAF.  

Keyword

 3D-structure; Acetylation; Cell cycle; Chromatin regulator; Complete proteome; Direct protein sequencing; Disease mutation; DNA-binding; Host-virus interaction; Methylation; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Repressor; Transcription; Transcription regulation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 928 AA 

Protein Sequence

Gene Ontology

 GO:0000785; C:chromatin; TAS:ProtInc.
 GO:0016605; C:PML body; IDA:UniProtKB.
 GO:0035189; C:Rb-E2F complex; TAS:BHF-UCL.
 GO:0005819; C:spindle; IEA:Compara.
 GO:0016514; C:SWI/SNF complex; TAS:BHF-UCL.
 GO:0050681; F:androgen receptor binding; NAS:UniProtKB.
 GO:0001047; F:core promoter binding; IDA:UniProtKB.
 GO:0019900; F:kinase binding; IDA:UniProtKB.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
 GO:0003713; F:transcription coactivator activity; NAS:UniProtKB.
 GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
 GO:0007050; P:cell cycle arrest; TAS:BHF-UCL.
 GO:0051301; P:cell division; IEA:Compara.
 GO:0048667; P:cell morphogenesis involved in neuron differentiation; IEA:Compara.
 GO:0006338; P:chromatin remodeling; TAS:BHF-UCL.
 GO:0048565; P:digestive tract development; IEA:Compara.
 GO:0043353; P:enucleate erythrocyte differentiation; IEA:Compara.
 GO:0034088; P:maintenance of mitotic sister chromatid cohesion; IMP:BHF-UCL.
 GO:0007093; P:mitotic cell cycle checkpoint; TAS:BHF-UCL.
 GO:0045445; P:myoblast differentiation; IMP:UniProtKB.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Compara.
 GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; TAS:BHF-UCL.
 GO:0006469; P:negative regulation of protein kinase activity; IPI:UniProtKB.
 GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; TAS:BHF-UCL.
 GO:0045879; P:negative regulation of smoothened signaling pathway; IEA:Compara.
 GO:0007070; P:negative regulation of transcription from RNA polymerase II promoter during mitosis; TAS:BHF-UCL.
 GO:0071930; P:negative regulation of transcription involved in G1/S phase of mitotic cell cycle; IEA:Compara.
 GO:0051402; P:neuron apoptotic process; IEA:Compara.
 GO:0042551; P:neuron maturation; IEA:Compara.
 GO:0031175; P:neuron projection development; IEA:Compara.
 GO:0045651; P:positive regulation of macrophage differentiation; IEA:Compara.
 GO:0045842; P:positive regulation of mitotic metaphase/anaphase transition; IMP:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
 GO:0071459; P:protein localization to chromosome, centromeric region; IMP:BHF-UCL.
 GO:0007265; P:Ras protein signal transduction; IEP:BHF-UCL.
 GO:0090230; P:regulation of centromere complex assembly; TAS:BHF-UCL.
 GO:0071922; P:regulation of cohesin localization to chromatin; IMP:BHF-UCL.
 GO:0043550; P:regulation of lipid kinase activity; IDA:UniProtKB.
 GO:0000083; P:regulation of transcription involved in G1/S phase of mitotic cell cycle; TAS:BHF-UCL.
 GO:0031134; P:sister chromatid biorientation; IMP:BHF-UCL.
 GO:0051146; P:striated muscle cell differentiation; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR013763; Cyclin-like.
 IPR024599; DUF3452_retinoblatoma-assoc.
 IPR002720; RB_A.
 IPR015652; Rb_associated.
 IPR002719; RB_B.
 IPR015030; Rb_C. 

Pfam

 PF11934; DUF3452
 PF01858; RB_A
 PF01857; RB_B
 PF08934; Rb_C 

SMART

 SM00385; CYCLIN 

PROSITE

  

PRINTS