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FLASH GENE
Symbol RB1 contributors: mct/shn - updated : 01-03-2017
HGNC name retinoblastoma 1
HGNC id 9884
Corresponding disease
DEL13Q14 chromosome 13q deletions including band q14
RB retinoblastoma
Location 13q14.2      Physical location : 48.877.882 - 49.056.024
Synonym name
  • retinoblastoma susceptibility protein
  • retinoblastoma-associated protein
  • Synonym symbol(s) OSRC, RB, p105-Rb, pp110, RP11-174I10.1, pRb
    DNA
    TYPE functioning gene
    STRUCTURE 178.14 kb     27 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    text structure
  • DNA binding sites
  • four GC-rich promoter elements (FREs) located at bp –308 to –188 of the promoter region
  • a conserved binding site for the E2F transcription factors, some of which are direct partners of RB and key downstream mediators of RB (Burkhart 2010)
  • two Sp1 binding sites: GC-box 1 (bp –65 to –56) and GC-box 2 (bp –18 to –9), the latter of which is also bound by ZBTB7A
  • MAPPING cloned Y linked N status confirmed
    Map cen - D13S287 - D13S164 - RB1 - D13S1307 - D13S165 - qter
    Physical map
    LOC220416 13q14.11 similar to Leucine-rich repeat protein SHOC-2 (Ras-binding protein Sur-8) LOC390403 13 similar to hypothetical protein FLJ20457 C13orf18 13q14.11 chromosome 13 open reading frame 18 LOC81993 13q14-q21 COX17 pseudogene CHDC1 13q14.11 calponin homology (CH) domain containing 1 ESD 13q14.1-q14.2 esterase D/formylglutathione hydrolase HTR2A 13q14.3 5-hydroxytryptamine (serotonin) receptor 2A SUCLA2 13q12.2-q13.3 succinate-CoA ligase, ADP-forming, beta subunit NUDT15 13q14.12 nudix (nucleoside diphosphate linked moiety X)-type motif 15 VDRIP 13q14.12 vitamin D receptor interacting protein ITM2B 13q14.3 integral membrane protein 2B RB1 13q14.2 retinoblastoma 1 (including osteosarcoma) P2RY5 13q14 purinergic receptor P2Y, G-protein coupled, 5 CHC1L 13q14.3 chromosome condensation 1-like CYSLTR2 13q14.12-p21.1 cysteinyl leukotriene receptor 2 LOC338099 13q13 proteasome activator subunit 2 pseudogene KIAA0970 13q14.11 proteasome activator subunit 2 pseudogene RAD17P2 13q14.3 RAD17 homolog (S. pombe) pseudogene 2 COX7CP1 13q14-q21 cytochrome c oxidase subunit VIIc pseudogene 1 LOC387924 13 similar to hypothetical protein FLJ10826 GPR38 13q14-q21 G protein-coupled receptor 38 CDADC1 13q14.12 cytidine and dCMP deaminase domain containing 1 FLJ12577 13q14.12 hypothetical protein FLJ12577 SETDB2 13q14 SET domain, bifurcated 2 PHF11 13q14.12 PHD finger protein 11 RCBTB1 13q14 regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein 1 ARLTS1 EBRP 13q12-q13 emopamil binding related protein, delta8-delta7 sterol isomerase related protein KPNA3 13q14.3 karyopherin alpha 3 (importin alpha 4) LOC220429 13q14.13 similar to Meningioma-expressed antigen 6/11 (MEA6) (MEA11) C13orf1 13q14 chromosome 13 open reading frame 1 RFP2 13q14 ret finger protein 2 KCNRG 13q14.11 potassium channel regulator DLEU2 13q14.2-q14.3 deleted in lymphocytic leukemia, 2 DLEU1 13q14.2-q14.3 deleted in lymphocytic leukemia, 1 FAM10A4 13q14.3 family with sequence similarity 10, member A4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 - 4772 106 928 - 1998 9468139
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Endocrinethyroid    
    Lymphoid/Immunelymph node   highly
    Nervousbrainbasal nuclei  moderately
    Respiratoryrespiratory tracttrachea  highly
     respiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a T/E1A-binding (pocket) domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to Rb1, Mus musculus
    ortholog to Rb1, Rattus norvegicus
    Homologene
    FAMILY
  • pocket protein family
  • retinoblastoma protein (RB) family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • plays an important role in the production and maintenance of the terminally differentiated phenotype of muscle cells
  • regulator of cell growth
  • essential roles in cochlear and vestibular hair cell maturation, function, and survival
  • functioning as a downstream effector of ABL that plays a positive role in survival of ABL-dependent tumor cells, including BCR/ABL-positive chronic myelogenous leukemia (CML)
  • co-expression of ZBTB16 and RB1 results in enhancement of transcriptional repression of ZBTB16 and E2F/Rb target genes, indicating functional co-operation between the two proteins
  • key regulator of cellular senescence
  • plays a critical role in mitotic chromosome condensation independently of G1-to-S-phase regulation
  • regulate several transcription factors that are master differentiation inducers
  • plays a key role in establishing fate choice between bone and brown adipose tissue
  • can mediate the response to DNA damage through modulation of ZNF350, a zinc finger-containing transcriptional repressor that can modulate the expression of GADD45A, a DNA damage response gene, to induce cell cycle arrest in response to DNA damage
  • tumor suppression by RB1 might involve coordinated regulation of both E2F and RBP2
  • RB1 has a nonredundant role in senescent cells by mediating heterochromatin formation at E2F1 targets
  • plays multiple roles in coordinating cell cycle progression to prevent aberrant ploidy in horizontal cells
  • role for RB1 in osteoblast differentiation
  • overlapping role for RB1 and RBL1 in cartilage development, endochondral ossification and enchondroma formation that reflects their coordination of cell-cycle exit at appropriate developmental stages
  • potential role for RB1 in regulating angiogenesis through activation of NOL7
  • CELLULAR PROCESS cell cycle, progression
    cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    RB pathway
    a component
  • RB1/RBBP8/CTBP1/E2F1 complex plays a critical role in ZNF350 transcriptional repression, and loss of this repression may contribute to cellular sensitivity of DNA damage, ultimately leading to carcinogenesis
  • INTERACTION
    DNA
  • AP-1 binding site within the c-jun and collagenase promoters
  • RNA
    small molecule
    protein
  • activates transcription of the human TGF-beta 2 gene
  • activating transcription factor 2, ATF2
  • retinoblastoma binding protein 4, RBBP4 and etinoblastoma binding protein 7, RBBP7
  • nuclear matrix protein p84
  • zinc finger protein RIZ
  • retinoblastoma-binding protein RBQ3
  • Pur alpha, PURA
  • nuclear tyrosine kinase Rak
  • heat shock 70 kDa protein 1, Hsp70
  • TATA-binding protein-associated factor TAFII250
  • c-Myc protein, Myc
  • BRM/SWI2-related gene 1, BRG1
  • lamin A, LMNA
  • serine/threonine protein kinase PITALRE
  • myogenic differentiation 1, MYOD1
  • protein phosphatase 1, catalytic subunit, alpha isozyme, PPP1CA
  • cellular transcription factor PU.1
  • E74-like factor 1 (ets domain transcription factor), ELF1
  • nuclear factor of interleukin 6, NF-IL6
  • E2F-1, E2F-2, and E2F-3
  • heat shock protein 75 kDa, HSP75
  • protein activator of the interferon-induced protein kinase, PACT
  • BCR-ABL
  • TFIIIB and TFIIIC2
  • HMG-box transcription factor 1, HBP1
  • TAF(II)250/TFIID
  • Trip230
  • human cytomegalovirus major immediate-early 86-kDa protein, IE2 86
  • DNA polymerase alpha, POLA
  • promyelocytic leukemia gene product, PML
  • minichromosome maintenance complex component 7, MCM7
  • androgen receptor, AR
  • B5T overexpressed gene protein, Bog
  • aryl hydrocarbon receptor, AHR
  • retinoblastoma binding protein 8, RBBP8
  • v-raf-1 murine leukemia viral oncogene homolog 1, RAF1
  • cyclin A1, CCNA1
  • c-Jun
  • paired box 5, PAX5
  • paired box 6, PAX6
  • Prohibitin, PHB
  • opoisomerase IIalpha
  • bright and dead ringer protein, BDP
  • p21 cyclin-dependent kinase, P21
  • BRCA1 protein complexes with the hypophosphorylated form of pRb
  • Gankyrin
  • RB-associated KRAB protein, RBaK
  • rb-binding protein Che-1, CHE1
  • p120E4F
  • insulin
  • RBP95
  • UBF
  • E1A-like inhibitor of differentiation 1, EID-1
  • represses RNA polymerase III transcription
  • SNAPc 43 kDa subunit, SNAP43 and SNAPc 50 kDa subunit, SNAP50
  • aryl hydrocarbon receptor, AhR
  • ErbB-3 binding protein 1, EBP1
  • SUV39H1 and HP1
  • FERTILIZATION INDEPENDENT ENDOSPERM, FIE
  • activating transcription factor 2, ATF2
  • de-ubiquitinating enzyme Unp
  • PKC beta 2
  • DNA (cytosine-5-)-methyltransferase 1, DNMT1
  • cdk9/cyclinT2 complex
  • paired box 2, PAX2
  • cyclophilin A, CYPA
  • MORF-related gene on chromosome 15, MRG15 and protein associated with MRG of 14 kDa, PAM14
  • Ski interacting protein, Skip
  • LAP2alpha, lamins A and C
  • peroxisome proliferator-activated receptor gamma, PPARgamma and Histone deacetylase 3, HDAC3
  • proline, glutamate and leucine rich protein 1, PELP1
  • Receptor of activated protein kinase C 1, RACK1
  • BCL2-associated athanogene, BAG1
  • CCAAT displacement protein, CDP
  • serpin plasminogen activator inhibitor 2, SERPINB2
  • CCAAT enhancer binding protein epsilon, C/EBPepsilon
  • Activating signal cointegrator-2, ASC2
  • with the N terminus of S-phase kinase-associated protein 2 (p45), SKP2
  • lin-9 homolog (C. elegans), LIN9
  • runt-related transcription factor 2, RUNX2
  • HIF-1alpha
  • cooperates with Mitf
  • H4K20 tri-methylating enzymes Suv4-20h1 and Suv4-20h2
  • Retinoblastoma-binding protein 2-homolog 1, RBBP2H1
  • viral and cellular LxCxE-motif proteins
  • tripartite motif containing 27, TRIM27
  • retinol binding protein 2, RBP2
  • phosphatidylinositol-4-phosphate 5-kinases and diacylglycerol kinase zeta, DGKzeta
  • tumor suppressor P205
  • protein arginine methyltransferase 2, PRMT2
  • high mobility group AT-hook 2, HMGA2
  • histone deacetylase 1, HDAC1 and pyrophosphatase (inorganic) 1, PP1
  • anaphase-promoting complex/cyclosome, APC/C
  • interaction between ZBTB16 and RB1 is mediated through the RB1 pocket and the region of ZBTB16 that lies between its transcriptional repression (poxvirus and zinc-finger, POZ) and DNA-binding (zinc-finger) domains
  • Aurora B, AURKB
  • E2F4 and RB1 play independent cell-intrinsic roles in fetal erythropoiesis
  • CDK5R1
  • acts as a negative regulator of ZNF350 transcription
  • KDM6A
  • catalytic subunit of protein phosphatase 1, PPP1CA
  • E2F1 which is dependent on the phosphorylation status of RB1
  • coordinates with E2F1 to regulate the ZNF350 promoter through the E2F motif
  • target for lysine methylation by SETD7
  • methylated at lysine 860 by SMYD2 (this modification permits direct binding of RB1 to the lysine methyl-binding protein L3MBTL, which may alter the function of RB1 in cells)
  • RBP1 binds to the pocket region of RB1 via an LXCXE motif and to the SAP30 subunit of the mSin3·HDAC complex
  • associates with and stabilizes pancreatic duodenal homeobox-1 (PDX1) that is essential for embryonic pancreas development and adult beta-cell function
  • interacting with RBP2 (RBP2 inhibits senescence and differentiation in RB1-defective tumor cells, and loss of RBP2 inhibits formation of RB1-defective endocrine tumors, suggesting that RBP2 also acts downstream of RB1)
  • RB1 protein selectively represses specific E2F1 target genes via a TAAC element in senescent cells
  • cooperative effect between CIC and RB1 in promoting G1 arrest is mediated, at least in part, by limiting CCNE expression
  • SMAD2 overexpression inhibits the proliferation of junctional epithelium (JE) cells by down-regulating MYC and up-regulating CDKN2B and CDKN1B, which resulted in an increase in RB1, leading to cell-cycle arrest
  • lysine methylation-dependent binding of TP53BP1 to the RB1 tumor suppressor
  • RB1 maintains quiescence and prevents premature senescence through upregulation of DNMT1 in mesenchymal stromal cells
  • role of KDM6B as a novel inducer of senescence-associated heterochromatin foci (SAHF), formation through demethylating RB1
  • SUMO1 conjugation of RB1 and LMNA is modulated by the SUMO protease SENP1 and sumoylation of both proteins is required for their interaction
  • MAZ is essential to bypass MYB promoter repression by RB1 family members and to induce MYB expression
  • cell & other
    REGULATION
    activated by KDM6A through the changes of histone H3 methylation on the promoters)
    repressed by Proto-oncogene FBI-1
    Other constitutively phosphorylated at tyrosine in ABL-dependent tumor cells (ABL phosphorylates RB1 specifically at Y805 within the C-terminal domain of the molecule)
    regulated by the three pocket proteins RBL1, RBL2
    suppressed by Cyclin D1
    acetylated by p300-Associated Factor, P/CAF
    degradated and functionally inactivated by caspase-3-like protease
    phosphorylated by serine/threonine protein kinase PITALRE
    phosphorylated by cyclin D2-cyclin-dependent kinase 4
    cell division cycle 2, CDC2
    phosphorylated by Aurora B
    can be methylated by SMYD2 at lysine 860, a highly conserved and novel site of modification
    ASSOCIATED DISORDERS
    corresponding disease(s) RB , DEL13Q14
    related resource Retinoblastoma, RB1 Mutation Database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in malignant fibrous histiocytoma
    tumoral     --low  
    promoting breast-tumor aggressiveness and rapid cell tumor proliferation
    tumoral   deletion    
    in pituitary tumor (somatotrophinoma)
    tumoral   LOH    
    in esophageal squamous cell carcinoma (concomitant loss of CDKN2A or not) and in hepatocellular carcinoma
    tumoral       loss of function
    in small cell lung carcinoma, in eye tumor
    tumoral       loss of function
    in developing retina induces genomic instability, but senescence can block transformation at the stage of retinoma
    constitutional       loss of function
    leads to the rapid degeneration of most retinal cells except horizontal cells, which persist as giant cells with aberrant centrosome content, DNA damage, and polyploidy/aneuploidy
    Susceptibility to ovarian carcinoma
    Variant & Polymorphism other associations of rs2854344 and rs4151620 with ovarian cancer risk
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    phosphorylated RB1 can be a molecular target for cancer therapy aimed at inducing apoptosis of ABL-dependent tumor cells, such as BCR/ABL-positive CML
    ANIMAL & CELL MODELS
  • expression of a viral oncogene, the simian virus 40 T antigen, in the retina of transgenic mice produces heritable ocular tumours with histological, ultrastructural and immunohistochemical features identical to those of human retinoblastoma
  • mice with an insertional mutation in exon 20 of the Rb-1 locus die before the 16th embryonic day with multiple defects
  • mice with Rb1 conditionnaly deleted in the central nervous system show an increase in neuronal number due to aberrant S phase entry without apoptosis
  • disruption of the retinoblastoma gene in mice leads to embryonic lethality in midgestation accompanied by defective erythropoiesis, inappropriate cell cycle activity and apoptosis in the central nervous system, peripheral nervous system and ocular lens
  • adult pRb(-/-) mice exhibit profound hearing loss due to progressive degeneration of the organ of Corti
  • mouse embryonic fibroblasts lacking the retinoblastoma genes RB1 display genomic instability
  • defective mitotic chromosome structure caused by mutant pRB accelerates loss of heterozygosity lead to earlier tumor formation in Trp53(+/-) mice