Browse RB1

Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus
Domain PF11934 Domain of unknown function (DUF3452)
PF01858 Retinoblastoma-associated protein A domain
PF01857 Retinoblastoma-associated protein B domain
PF08934 Rb C-terminal domain
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, 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). 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.

> Gene Ontology
 
Biological Process GO:0000070 mitotic sister chromatid segregation
GO:0000075 cell cycle checkpoint
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0000819 sister chromatid segregation
GO:0001558 regulation of cell growth
GO:0001894 tissue homeostasis
GO:0001933 negative regulation of protein phosphorylation
GO:0002262 myeloid cell homeostasis
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0002761 regulation of myeloid leukocyte differentiation
GO:0002763 positive regulation of myeloid leukocyte differentiation
GO:0006338 chromatin remodeling
GO:0006469 negative regulation of protein kinase activity
GO:0007050 cell cycle arrest
GO:0007059 chromosome segregation
GO:0007062 sister chromatid cohesion
GO:0007063 regulation of sister chromatid cohesion
GO:0007064 mitotic sister chromatid cohesion
GO:0007067 mitotic nuclear division
GO:0007068 negative regulation of transcription during mitosis
GO:0007070 negative regulation of transcription from RNA polymerase II promoter during mitosis
GO:0007088 regulation of mitotic nuclear division
GO:0007091 metaphase/anaphase transition of mitotic cell cycle
GO:0007093 mitotic cell cycle checkpoint
GO:0007224 smoothened signaling pathway
GO:0007265 Ras protein signal transduction
GO:0007346 regulation of mitotic cell cycle
GO:0007517 muscle organ development
GO:0007519 skeletal muscle tissue development
GO:0008589 regulation of smoothened signaling pathway
GO:0008608 attachment of spindle microtubules to kinetochore
GO:0009410 response to xenobiotic stimulus
GO:0009755 hormone-mediated signaling pathway
GO:0010948 negative regulation of cell cycle process
GO:0010965 regulation of mitotic sister chromatid separation
GO:0014706 striated muscle tissue development
GO:0016049 cell growth
GO:0019216 regulation of lipid metabolic process
GO:0021700 developmental maturation
GO:0030071 regulation of mitotic metaphase/anaphase transition
GO:0030099 myeloid cell differentiation
GO:0030218 erythrocyte differentiation
GO:0030225 macrophage differentiation
GO:0030518 intracellular steroid hormone receptor signaling pathway
GO:0030521 androgen receptor signaling pathway
GO:0030522 intracellular receptor signaling pathway
GO:0031134 sister chromatid biorientation
GO:0033044 regulation of chromosome organization
GO:0033045 regulation of sister chromatid segregation
GO:0033047 regulation of mitotic sister chromatid segregation
GO:0033673 negative regulation of kinase activity
GO:0034085 establishment of sister chromatid cohesion
GO:0034086 maintenance of sister chromatid cohesion
GO:0034088 maintenance of mitotic sister chromatid cohesion
GO:0034101 erythrocyte homeostasis
GO:0034349 glial cell apoptotic process
GO:0034502 protein localization to chromosome
GO:0034508 centromere complex assembly
GO:0035914 skeletal muscle cell differentiation
GO:0042326 negative regulation of phosphorylation
GO:0042551 neuron maturation
GO:0042692 muscle cell differentiation
GO:0043353 enucleate erythrocyte differentiation
GO:0043388 positive regulation of DNA binding
GO:0043401 steroid hormone mediated signaling pathway
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043550 regulation of lipid kinase activity
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0044784 metaphase/anaphase transition of cell cycle
GO:0044843 cell cycle G1/S phase transition
GO:0045445 myoblast differentiation
GO:0045637 regulation of myeloid cell differentiation
GO:0045639 positive regulation of myeloid cell differentiation
GO:0045649 regulation of macrophage differentiation
GO:0045651 positive regulation of macrophage differentiation
GO:0045786 negative regulation of cell cycle
GO:0045787 positive regulation of cell cycle
GO:0045840 positive regulation of mitotic nuclear division
GO:0045842 positive regulation of mitotic metaphase/anaphase transition
GO:0045879 negative regulation of smoothened signaling pathway
GO:0045896 regulation of transcription during mitosis
GO:0045930 negative regulation of mitotic cell cycle
GO:0045931 positive regulation of mitotic cell cycle
GO:0046021 regulation of transcription from RNA polymerase II promoter, mitotic
GO:0048469 cell maturation
GO:0048545 response to steroid hormone
GO:0048565 digestive tract development
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048871 multicellular organismal homeostasis
GO:0048872 homeostasis of number of cells
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051098 regulation of binding
GO:0051099 positive regulation of binding
GO:0051101 regulation of DNA binding
GO:0051146 striated muscle cell differentiation
GO:0051304 chromosome separation
GO:0051306 mitotic sister chromatid separation
GO:0051348 negative regulation of transferase activity
GO:0051402 neuron apoptotic process
GO:0051783 regulation of nuclear division
GO:0051785 positive regulation of nuclear division
GO:0051983 regulation of chromosome segregation
GO:0051984 positive regulation of chromosome segregation
GO:0055123 digestive system development
GO:0060249 anatomical structure homeostasis
GO:0060537 muscle tissue development
GO:0060538 skeletal muscle organ development
GO:0065004 protein-DNA complex assembly
GO:0070997 neuron death
GO:0071168 protein localization to chromatin
GO:0071383 cellular response to steroid hormone stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071459 protein localization to chromosome, centromeric region
GO:0071466 cellular response to xenobiotic stimulus
GO:0071824 protein-DNA complex subunit organization
GO:0071921 cohesin loading
GO:0071922 regulation of cohesin loading
GO:0071930 negative regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0090068 positive regulation of cell cycle process
GO:0090230 regulation of centromere complex assembly
GO:0097284 hepatocyte apoptotic process
GO:0098813 nuclear chromosome segregation
GO:1901970 positive regulation of mitotic sister chromatid separation
GO:1901987 regulation of cell cycle phase transition
GO:1901988 negative regulation of cell cycle phase transition
GO:1901989 positive regulation of cell cycle phase transition
GO:1901990 regulation of mitotic cell cycle phase transition
GO:1901991 negative regulation of mitotic cell cycle phase transition
GO:1901992 positive regulation of mitotic cell cycle phase transition
GO:1902099 regulation of metaphase/anaphase transition of cell cycle
GO:1902101 positive regulation of metaphase/anaphase transition of cell cycle
GO:1902105 regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1902806 regulation of cell cycle G1/S phase transition
GO:1902807 negative regulation of cell cycle G1/S phase transition
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1904019 epithelial cell apoptotic process
GO:2000045 regulation of G1/S transition of mitotic cell cycle
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
GO:2000677 regulation of transcription regulatory region DNA binding
GO:2000679 positive regulation of transcription regulatory region DNA binding
GO:2001252 positive regulation of chromosome organization
Molecular Function GO:0001047 core promoter binding
GO:0001085 RNA polymerase II transcription factor binding
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0003713 transcription coactivator activity
GO:0008134 transcription factor binding
GO:0031625 ubiquitin protein ligase binding
GO:0033613 activating transcription factor binding
GO:0035257 nuclear hormone receptor binding
GO:0035258 steroid hormone receptor binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0050681 androgen receptor binding
GO:0051219 phosphoprotein binding
GO:0051427 hormone receptor binding
Cellular Component GO:0000307 cyclin-dependent protein kinase holoenzyme complex
GO:0000785 chromatin
GO:0005667 transcription factor complex
GO:0005819 spindle
GO:0008023 transcription elongation factor complex
GO:0008024 cyclin/CDK positive transcription elongation factor complex
GO:0016514 SWI/SNF complex
GO:0016604 nuclear body
GO:0016605 PML body
GO:0019908 nuclear cyclin-dependent protein kinase holoenzyme complex
GO:0032806 carboxy-terminal domain protein kinase complex
GO:0035189 Rb-E2F complex
GO:0044798 nuclear transcription factor complex
GO:0061695 transferase complex, transferring phosphorus-containing groups
GO:0070603 SWI/SNF superfamily-type complex
GO:0090544 BAF-type complex
GO:0090575 RNA polymerase II transcription factor complex
GO:1902554 serine/threonine protein kinase complex
GO:1902911 protein kinase complex
> KEGG and Reactome Pathway
 
KEGG hsa04110 Cell cycle
Reactome R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-2299718: Condensation of Prophase Chromosomes
R-HSA-69656: Cyclin A
R-HSA-69231: Cyclin D associated events in G1
R-HSA-69202: Cyclin E associated events during G1/S transition
R-HSA-2559586: DNA Damage/Telomere Stress Induced Senescence
R-HSA-69306: DNA Replication
R-HSA-113510: E2F mediated regulation of DNA replication
R-HSA-2559584: Formation of Senescence-Associated Heterochromatin Foci (SAHF)
R-HSA-69236: G1 Phase
R-HSA-69206: G1/S Transition
R-HSA-113501: Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-68886: M Phase
R-HSA-453279: Mitotic G1-G1/S phases
R-HSA-68875: Mitotic Prophase
R-HSA-68949: Orc1 removal from chromatin
R-HSA-69200: Phosphorylation of proteins involved in G1/S transition by active Cyclin E
R-HSA-69304: Regulation of DNA replication
R-HSA-69300: Removal of licensing factors from origins
R-HSA-69242: S Phase
R-HSA-69052: Switching of origins to a post-replicative state
R-HSA-69239: Synthesis of DNA
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between RB1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between RB1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24824777Hepatocellular CarcinomaPromote immunityWe found that RB depletion in hepatoma cells resulted in a compromised immunological response to multiple stimuli and reduced the potential of these cells to recruit myeloid cells. Viral-mediated liver-specific RB deletion in vivo led to the induction of genes associated with proliferation and cell cycle entry as well as the significant attenuation of genes associated with immune function, as evidenced by decreases in cytokine and chemokine expression, leukocyte recruitment, and hepatic inflammation. To determine if these changes in gene expression were instructive in human disease, we compared our liver-specific RB-loss gene signature to existing profiles of HCC and found that this signature was associated with disease progression and confers a worse prognosis.
24231354OsteosarcomaPromote immunityImmune response to RB1-regulated senescence limits radiation-induced osteosarcoma formation. Ionizing radiation (IR) and germline mutations in the retinoblastoma tumor suppressor gene (RB1) are the strongest risk factors for developing osteosarcoma. Recapitulating the human predisposition, we found that Rb1+/- mice exhibited accelerated development of IR-induced osteosarcoma, with a latency of 39 weeks.
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of RB1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of RB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.4110.196
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.5590.774
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.3070.824
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3780.133
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3220.851
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.4490.834
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0480.912
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0430.982
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1170.955
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2080.884
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7130.748
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2480.0131
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of RB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.45.51.90.66
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.46.80.61
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.112.5-1.41
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592011.18.91
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RB1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RB1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RB1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RB1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of RB1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between RB1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolRB1
Nameretinoblastoma 1
Aliases RB; PPP1R130; prepro-retinoblastoma-associated protein; protein phosphatase 1, regulatory subunit 130; OSRC; ......
Chromosomal Location13q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting RB1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting RB1.
ID Name Drug Type Targets #Targets
DB00030Insulin HumanBiotechCPE, CTSD, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV, PCSK1, PCSK2, RB1, ......12
DB00071Insulin PorkBiotechCPE, CTSD, HLA-DQA2, HLA-DQB1, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV ......14