======= RB1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RB1
  * **<color #00a2e8>Official Name</color>**: RB transcriptional corepressor 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5925|5925]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P06400|P06400]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RB1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RB1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/614041|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000250, ECO:0000269|PubMed:15084261}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|RB A|
|RB B|
|DUF3452|
|Rb C|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|Rb-E2F complex|
|positive regulation of collagen fibril organization|
|negative regulation of tau-protein kinase activity|
|negative regulation of transcription involved in G1/S transition of mitotic cell cycle|
|sister chromatid biorientation|
|negative regulation of myofibroblast differentiation|
|maintenance of mitotic sister chromatid cohesion|
|maintenance of sister chromatid cohesion|
|regulation of myofibroblast differentiation|
|regulation of cohesin loading|
|glial cell apoptotic process|
|regulation of centromere complex assembly|
|regulation of collagen fibril organization|
|importin-alpha family protein binding|
|regulation of protein localization to chromatin|
|enucleate erythrocyte differentiation|
|cyclin/CDK positive transcription elongation factor complex|
|positive regulation of mitotic sister chromatid separation|
|positive regulation of mitotic metaphase/anaphase transition|
|positive regulation of metaphase/anaphase transition of cell cycle|
|RNA polymerase II regulatory region DNA binding|
|regulation of tau-protein kinase activity|
|positive regulation of chromosome separation|
|hepatocyte apoptotic process|
|positive regulation of macrophage differentiation|
|mitotic sister chromatid cohesion|
|positive regulation of mitotic sister chromatid segregation|
|protein localization to chromosome, centromeric region|
|SWI/SNF complex|
|attachment of spindle microtubules to kinetochore|
|positive regulation of extracellular matrix organization|
|regulation of macrophage differentiation|
|regulation of sister chromatid cohesion|
|positive regulation of transcription regulatory region DNA binding|
|epithelial cell apoptotic process|
|regulation of transcription involved in G1/S transition of mitotic cell cycle|
|aortic valve morphogenesis|
|positive regulation of chromosome segregation|
|negative regulation of smoothened signaling pathway|
|proximal promoter sequence-specific DNA binding|
|aortic valve development|
|disordered domain specific binding|
|phosphoprotein binding|
|myoblast differentiation|
|androgen receptor signaling pathway|
|semi-lunar valve development|
|neuron maturation|
|regulation of extracellular matrix organization|
|neuron apoptotic process|
|androgen receptor binding|
|negative regulation of cold-induced thermogenesis|
|sister chromatid cohesion|
|skeletal muscle cell differentiation|
|regulation of mitotic metaphase/anaphase transition|
|neuron death|
|regulation of transcription regulatory region DNA binding|
|heart valve morphogenesis|
|positive regulation of mitotic nuclear division|
|regulation of metaphase/anaphase transition of cell cycle|
|RNA polymerase II activating transcription factor binding|
|positive regulation of myeloid leukocyte differentiation|
|positive regulation of DNA binding|
|regulation of mitotic sister chromatid separation|
|heart valve development|
|regulation of chromosome separation|
|regulation of lipid kinase activity|
|protein localization to chromosome|
|positive regulation of nuclear division|
|regulation of mitotic sister chromatid segregation|
|intracellular steroid hormone receptor signaling pathway|
|positive regulation of mitotic cell cycle phase transition|
|regulation of smoothened signaling pathway|
|erythrocyte differentiation|
|regulation of sister chromatid segregation|
|erythrocyte homeostasis|
|positive regulation of myeloid cell differentiation|
|kinase binding|
|positive regulation of cell cycle phase transition|
|PML body|
|negative regulation of G1/S transition of mitotic cell cycle|
|regulation of chromosome segregation|
|negative regulation of cell cycle G1/S phase transition|
|myeloid cell homeostasis|
|mitotic sister chromatid segregation|
|chromatin|
|regulation of myeloid leukocyte differentiation|
|G1/S transition of mitotic cell cycle|
|spindle|
|steroid hormone mediated signaling pathway|
|cell cycle G1/S phase transition|
|skeletal muscle tissue development|
|negative regulation of epithelial cell proliferation|
|regulation of DNA binding|
|digestive tract development|
|negative regulation of protein serine/threonine kinase activity|
|skeletal muscle organ development|
|anatomical structure maturation|
|negative regulation of inflammatory response|
|sister chromatid segregation|
|digestive system development|
|regulation of cold-induced thermogenesis|
|mitotic nuclear division|
|cell cycle arrest|
|positive regulation of leukocyte differentiation|
|regulation of G1/S transition of mitotic cell cycle|
|positive regulation of mitotic cell cycle|
|mitotic cell cycle checkpoint|
|cell maturation|
|negative regulation of DNA-binding transcription factor activity|
|chromatin remodeling|
|intracellular receptor signaling pathway|
|regulation of cell cycle G1/S phase transition|
|regulation of mitotic nuclear division|
|hormone-mediated signaling pathway|
|positive regulation of chromosome organization|
|positive regulation of binding|
|cellular response to xenobiotic stimulus|
|positive regulation of hemopoiesis|
|cellular response to steroid hormone stimulus|
|tissue homeostasis|
|regulation of nuclear division|
|cell cycle checkpoint|
|positive regulation of supramolecular fiber organization|
|homeostasis of number of cells|
|striated muscle cell differentiation|
|transcription factor complex|
|negative regulation of defense response|
|negative regulation of mitotic cell cycle phase transition|
|nuclear chromosome segregation|
|myeloid cell differentiation|
|negative regulation of apoptotic signaling pathway|
|negative regulation of protein kinase activity|
|regulation of myeloid cell differentiation|
|negative regulation of cell cycle phase transition|
|developmental maturation|
|muscle cell differentiation|
|negative regulation of kinase activity|
|Ras protein signal transduction|
|mitotic cell cycle phase transition|
|regulation of leukocyte differentiation|
|chromosome segregation|
|negative regulation of transferase activity|
|cell cycle phase transition|
|transcription coactivator activity|
|striated muscle tissue development|
|nuclear division|
|positive regulation of cell cycle process|
|ubiquitin protein ligase binding|
|muscle organ development|
|muscle tissue development|
|response to xenobiotic stimulus|
|negative regulation of mitotic cell cycle|
|organelle fission|
|small GTPase mediated signal transduction|
|multicellular organismal homeostasis|
|negative regulation of cell cycle process|
|response to steroid hormone|
|transcription factor binding|
|regulation of epithelial cell proliferation|
|regulation of inflammatory response|
|anatomical structure homeostasis|
|regulation of chromosome organization|
|regulation of supramolecular fiber organization|
|negative regulation of response to external stimulus|
|positive regulation of cell cycle|
|regulation of binding|
|regulation of lipid metabolic process|
|regulation of apoptotic signaling pathway|
|negative regulation of protein phosphorylation|
|regulation of mitotic cell cycle phase transition|
|regulation of cell growth|
|regulation of DNA-binding transcription factor activity|
|cell morphogenesis involved in neuron differentiation|
|negative regulation of phosphorylation|
|regulation of cell cycle phase transition|
|regulation of hemopoiesis|
|regulation of protein complex assembly|
|muscle structure development|
|cell division|
|regulation of protein serine/threonine kinase activity|
|cellular response to lipid|
|heart development|
|regulation of cellular protein localization|
|cellular response to organic cyclic compound|
|hemopoiesis|
|cell morphogenesis involved in differentiation|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|negative regulation of cell cycle|
|negative regulation of protein modification process|
|mitotic cell cycle process|
|cellular response to hormone stimulus|
|hematopoietic or lymphoid organ development|
|positive regulation of organelle organization|
|regulation of mitotic cell cycle|
|immune system development|
|neuron projection development|
|regulation of growth|
|negative regulation of cell population proliferation|
|DNA-binding transcription factor activity|
|mitotic cell cycle|
|chromatin organization|
|viral process|
|negative regulation of cell differentiation|
|cell morphogenesis|
|protein localization to organelle|
|regulation of cell cycle process|
|regulation of defense response|
|symbiotic process|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|neuron development|
|interspecies interaction between organisms|
|cellular component morphogenesis|
|tube development|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|circulatory system development|
|regulation of kinase activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cellular localization|
|response to organic cyclic compound|
|apoptotic process|
|negative regulation of developmental process|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|regulation of transferase activity|
|negative regulation of cell death|
|cell cycle process|
|neuron differentiation|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|programmed cell death|
|chromosome organization|
|identical protein binding|
|cell death|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|plasma membrane bounded cell projection organization|
|negative regulation of molecular function|
|positive regulation of immune system process|
|cell projection organization|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|regulation of organelle organization|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|regulation of programmed cell death|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|regulation of protein modification process|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp38|Wortmannin 5μM R00 exp38]]|1.9|
|[[:results:exp81|Selumetinib 20μM R02 exp81]]|1.99|
|[[:results:exp2|5-Fluorouracil 20μM R00 exp2]]|2.04|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|2.08|
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|2.11|
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|2.13|
|[[:results:exp83|Trametinib 10μM R02 exp83]]|2.21|
|[[:results:exp66|BI-D1870 3.15μM R02 exp66]]|2.65|
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|3.42|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|3.94|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|4.16|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|4.92|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|7.23|
|[[:results:exp382|Palbociclib 1μM R07 exp382]]|7.97|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rfx7|RFX7]]|0.428|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 14608
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.76 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RB1 Expression in NALM6 Cells: 7.76'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>