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Protein

Retinoblastoma-associated protein

Gene

RB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • core promoter binding Source: UniProtKB
  • DNA binding Source: ProtInc
  • kinase binding Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • cell cycle arrest Source: BHF-UCL
  • cell cycle checkpoint Source: ProtInc
  • cell division Source: Ensembl
  • cell morphogenesis involved in neuron differentiation Source: Ensembl
  • cellular response to xenobiotic stimulus Source: Ensembl
  • chromatin modification Source: UniProtKB-KW
  • chromatin remodeling Source: BHF-UCL
  • digestive tract development Source: Ensembl
  • enucleate erythrocyte differentiation Source: Ensembl
  • G1/S transition of mitotic cell cycle Source: Reactome
  • glial cell apoptotic process Source: Ensembl
  • hepatocyte apoptotic process Source: Ensembl
  • maintenance of mitotic sister chromatid cohesion Source: BHF-UCL
  • mitotic cell cycle checkpoint Source: BHF-UCL
  • myoblast differentiation Source: UniProtKB
  • negative regulation of epithelial cell proliferation Source: Ensembl
  • negative regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
  • negative regulation of gene expression Source: MGI
  • negative regulation of protein kinase activity Source: UniProtKB
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of smoothened signaling pathway Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter during mitosis Source: BHF-UCL
  • negative regulation of transcription involved in G1/S transition of mitotic cell cycle Source: Ensembl
  • neuron apoptotic process Source: Ensembl
  • neuron maturation Source: Ensembl
  • neuron projection development Source: Ensembl
  • positive regulation of macrophage differentiation Source: Ensembl
  • positive regulation of mitotic metaphase/anaphase transition Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • positive regulation of transcription regulatory region DNA binding Source: MGI
  • protein localization to chromosome, centromeric region Source: BHF-UCL
  • Ras protein signal transduction Source: BHF-UCL
  • regulation of cell growth Source: Ensembl
  • regulation of centromere complex assembly Source: BHF-UCL
  • regulation of cohesin loading Source: BHF-UCL
  • regulation of lipid kinase activity Source: UniProtKB
  • regulation of mitotic cell cycle Source: BHF-UCL
  • regulation of transcription involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
  • sister chromatid biorientation Source: BHF-UCL
  • skeletal muscle cell differentiation Source: Ensembl
  • striated muscle cell differentiation Source: Ensembl
  • tissue homeostasis Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Repressor

Keywords - Biological processi

Cell cycle, Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139687-MONOMER.
ReactomeiR-HSA-113501. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
R-HSA-2299718. Condensation of Prophase Chromosomes.
R-HSA-2559584. Formation of Senescence-Associated Heterochromatin Foci (SAHF).
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-69200. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
R-HSA-69202. Cyclin E associated events during G1/S transition.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-69656. Cyclin A:Cdk2-associated events at S phase entry.
SignaLinkiP06400.
SIGNORiP06400.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoblastoma-associated protein
Alternative name(s):
p105-Rb
pRb
Short name:
Rb
pp110
Gene namesi
Name:RB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:9884. RB1.

Subcellular locationi

  • Nucleus 1 Publication

GO - Cellular componenti

  • chromatin Source: ProtInc
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
  • Rb-E2F complex Source: BHF-UCL
  • spindle Source: Ensembl
  • SWI/SNF complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Childhood cancer retinoblastoma (RB)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCongenital 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.
See also OMIM:180200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00557272E → Q in RB. 1 Publication1
Natural variantiVAR_005573137E → D in RB; unilateral form. 1 PublicationCorresponds to variant rs3092902dbSNPEnsembl.1
Natural variantiVAR_005574185I → T in RB. 1 Publication1
Natural variantiVAR_010045310G → E in RB; unknown pathological significance. 1 PublicationCorresponds to variant rs200844292dbSNPEnsembl.1
Natural variantiVAR_010046358R → G in RB. 1 Publication1
Natural variantiVAR_005575358R → Q in RB. Corresponds to variant rs767011440dbSNPEnsembl.1
Natural variantiVAR_010048447K → Q in RB. 1 Publication1
Natural variantiVAR_005576457M → R in RB. 1 Publication1
Natural variantiVAR_005577480Missing in RB; mild form. 1 Publication1
Natural variantiVAR_011580500R → G in RB. 1 Publication1
Natural variantiVAR_010049530K → R in RB. 1 Publication1
Natural variantiVAR_005578549H → Y in RB. 1 Publication1
Natural variantiVAR_005579567S → L in RB. 2 PublicationsCorresponds to variant rs137853292dbSNPEnsembl.1
Natural variantiVAR_011581616K → E in RB. 1 Publication1
Natural variantiVAR_005580635A → P in RB. 1 Publication1
Natural variantiVAR_005581654V → E in RB. 1 Publication1
Natural variantiVAR_010050657L → P in RB. 1 Publication1
Natural variantiVAR_005582661R → W in RB; mild form. 4 PublicationsCorresponds to variant rs137853294dbSNPEnsembl.1
Natural variantiVAR_005583662L → P in RB. 1 Publication1
Natural variantiVAR_005584673H → P in RB. 1
Natural variantiVAR_005585685Q → P in RB. 1 Publication1
Natural variantiVAR_005586706C → Y in RB. 1
Natural variantiVAR_005587712C → R in RB. 1 PublicationCorresponds to variant rs137853296dbSNPEnsembl.1
Natural variantiVAR_005588803N → K in RB. 1 Publication1
Bladder cancer (BLC)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:109800
Osteogenic sarcoma (OSRC)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA sarcoma originating in bone-forming cells, affecting the ends of long bones.
See also OMIM:259500

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi821T → A: Abolishes interaction with Pocket domain; when associated with A-826. 1 Publication1
Mutagenesisi826T → A: Abolishes interaction with Pocket domain; when associated with A-821. 1 Publication1
Mutagenesisi860K → R: Abolishes monomethylation by SMYD2 and subsequent interaction with L3MBTL1. 1 Publication1
Mutagenesisi870K → R: Does not affect the ability to be methylated by SMYD2; when associated with 873-R-R-874. 1 Publication1
Mutagenesisi873 – 874KK → R: Does not affect the ability to be methylated by SMYD2; when associated with 873-R-R-874. 2 Publications2
Mutagenesisi873 – 874KK → RR: Does not alter Rb localization in cycling cells, but mislocalizes to the cytoplasm during keratinocytes differentiation. 2 Publications2

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi5925.
MalaCardsiRB1.
MIMi109800. phenotype.
180200. phenotype.
259500. phenotype.
OpenTargetsiENSG00000139687.
Orphaneti357027. Familial retinoblastoma.
1587. Monosomy 13q14.
357034. Unilateral retinoblastoma.
PharmGKBiPA295.

Chemistry databases

ChEMBLiCHEMBL5288.
DrugBankiDB00030. Insulin Regular.

Polymorphism and mutation databases

BioMutaiRB1.
DMDMi132164.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001678362 – 928Retinoblastoma-associated proteinAdd BLAST927

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N,N-dimethylprolineBy similarity1
Modified residuei37PhosphoserineCombined sources1
Modified residuei249Phosphoserine; by CDK1Combined sources1 Publication1
Modified residuei252Phosphothreonine; by CDK1Combined sources1 Publication1
Modified residuei356PhosphothreonineCombined sources1
Modified residuei373Phosphothreonine; by CDK1Combined sources1 Publication1
Modified residuei567Phosphoserine; by CDK21 Publication1
Modified residuei608PhosphoserineBy similarity1
Modified residuei612Phosphoserine; by CHEK2 and CHEK1Combined sources1 Publication1
Modified residuei624PhosphoserineCombined sources1
Modified residuei780PhosphoserineCombined sources1
Modified residuei788PhosphoserineCombined sources1
Modified residuei795PhosphoserineCombined sources1
Modified residuei807Phosphoserine; by CDK1 and CDK3Combined sources2 Publications1
Modified residuei810N6-methyllysine; by SMYD21 Publication1
Modified residuei811Phosphoserine; by CDK1 and CDK3Combined sources2 Publications1
Modified residuei821Phosphothreonine; by CDK6Combined sources2 Publications1
Modified residuei823PhosphothreonineCombined sources1
Modified residuei826Phosphothreonine; by CDK4Combined sources2 Publications1
Modified residuei841PhosphothreonineCombined sources1
Modified residuei855PhosphoserineCombined sources1
Modified residuei860N6-methyllysine; by SMYD21 Publication1
Modified residuei873N6-acetyllysine; by PCAF1 Publication1
Modified residuei874N6-acetyllysine; by PCAF1 Publication1

Post-translational modificationi

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 (By similarity).By similarity
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.By similarity9 Publications
Acetylation at Lys-873 and Lys-874 regulates subcellular localization, at least during keratinocytes differentiation.1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP06400.
MaxQBiP06400.
PaxDbiP06400.
PeptideAtlasiP06400.
PRIDEiP06400.

PTM databases

iPTMnetiP06400.
PhosphoSitePlusiP06400.

Miscellaneous databases

PMAP-CutDBP06400.

Expressioni

Tissue specificityi

Expressed in the retina.

Gene expression databases

BgeeiENSG00000139687.
CleanExiHS_RB1.
ExpressionAtlasiP06400. baseline and differential.
GenevisibleiP06400. HS.

Organism-specific databases

HPAiCAB000095.
CAB016687.
HPA050082.

Interactioni

Subunit structurei

Interacts with ATAD5. Interacts with PRMT2, CDK1 and CDK2 (By similarity). The hypophosphorylated form interacts with and sequesters the E2F1 transcription factor. Interacts with heterodimeric E2F/DP transcription factor complexes containing TFDP1 and either E2F1, E2F3, E2F4 or E2F5, or TFDP2 and E2F4. The unphosphorylated form interacts with EID1, ARID3B, KDM5A, SUV39H1, MJD2A/JHDM3A and THOC1. Interacts with the N-terminal domain of TAF1. Interacts with SNW1, AATF, DNMT1, LIN9, LMNA, KMT5B, KMT5C, PELP1, UHRF2 and TMPO-alpha. May interact with NDC80. Interacts with GRIP1 and UBR4. Interacts with ARID4A and KDM5B. Interacts with E4F1 and LIMD1. Interacts with SMARCA4/BRG1 AND HDAC1 (By similarity). Interacts with PSMA3 and USP4. Interacts (when methylated at Lys-860) with L3MBTL1. Interacts with CHEK2; phosphorylates RB1. Interacts with CEBPA (PubMed:15107404). Interacts with adenovirus E1A protein, HPV E7 protein and SV40 large T antigen. Interacts with human cytomegalovirus/HHV-5 protein UL123. P-TEFB complex interacts with RB1; promotes phosphorylation of RB1 (PubMed:12037672).By similarity36 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-491274,EBI-491274
P030706EBI-491274,EBI-617698From a different organism.
P032559EBI-491274,EBI-2603114From a different organism.
P03255-12EBI-491274,EBI-6692439From a different organism.
P03255-23EBI-491274,EBI-6859460From a different organism.
CDK2P249413EBI-491274,EBI-375096
Cdk4P302852EBI-491274,EBI-847225From a different organism.
CenpfQ155P74EBI-491274,EBI-2211248From a different organism.
CHEK1O147573EBI-491274,EBI-974488
CHEK2O960173EBI-491274,EBI-1180783
DGKZQ13574-26EBI-491274,EBI-715527
DYRK1AQ136273EBI-491274,EBI-1053596
DYRK1BQ9Y4633EBI-491274,EBI-634187
E2F1Q0109420EBI-491274,EBI-448924
E2F2Q142093EBI-491274,EBI-718476
E2F3O007164EBI-491274,EBI-765551
E7A0MPS72EBI-491274,EBI-7014709From a different organism.
E7P0312922EBI-491274,EBI-866453From a different organism.
E7P040203EBI-491274,EBI-7005254From a different organism.
E7P064643EBI-491274,EBI-6944797From a different organism.
E7P064652EBI-491274,EBI-963841From a different organism.
E7P067883EBI-491274,EBI-1776887From a different organism.
FOXO3O435242EBI-491274,EBI-1644164
FRKP426853EBI-491274,EBI-1383583
GRB2P629934EBI-491274,EBI-401755
HBP1O603812EBI-491274,EBI-954175
HDAC1Q135474EBI-491274,EBI-301834
Hmga2P529275EBI-491274,EBI-912574From a different organism.
Ifi202Q9R0025EBI-491274,EBI-3043899From a different organism.
IRF3Q146532EBI-491274,EBI-2650369
MAPK14Q165394EBI-491274,EBI-73946
MDM2Q009874EBI-491274,EBI-389668
MDM4O151514EBI-491274,EBI-398437
NCOA6Q146863EBI-491274,EBI-78670
NEFMP071972EBI-491274,EBI-1105035
ospFQ8VSP92EBI-491274,EBI-6506625From a different organism.
PA2G4Q9UQ804EBI-491274,EBI-924893
PPP1CAP621362EBI-491274,EBI-357253
PRMT2P553453EBI-491274,EBI-78458
PURAQ005776EBI-491274,EBI-1045860
RAF1P040493EBI-491274,EBI-365996
RNF40O751503EBI-491274,EBI-744408
SETD7Q8WTS64EBI-491274,EBI-1268586
Sirt1Q923E44EBI-491274,EBI-1802585From a different organism.
Smarca4Q3TKT44EBI-491274,EBI-1210244From a different organism.
UHRF2Q96PU44EBI-491274,EBI-625304
USP7Q930098EBI-491274,EBI-302474

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111860. 227 interactors.
DIPiDIP-582N.
IntActiP06400. 121 interactors.
MINTiMINT-98847.
STRINGi9606.ENSP00000267163.

Chemistry databases

BindingDBiP06400.

Structurei

Secondary structure

1928
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi55 – 63Combined sources9
Helixi68 – 82Combined sources15
Helixi95 – 110Combined sources16
Helixi117 – 124Combined sources8
Helixi128 – 135Combined sources8
Helixi142 – 172Combined sources31
Beta strandi180 – 182Combined sources3
Helixi188 – 204Combined sources17
Beta strandi207 – 209Combined sources3
Helixi212 – 228Combined sources17
Helixi232 – 234Combined sources3
Turni237 – 240Combined sources4
Helixi241 – 243Combined sources3
Helixi272 – 281Combined sources10
Helixi285 – 294Combined sources10
Helixi296 – 299Combined sources4
Helixi302 – 306Combined sources5
Helixi314 – 328Combined sources15
Helixi333 – 338Combined sources6
Helixi341 – 343Combined sources3
Helixi347 – 353Combined sources7
Helixi382 – 391Combined sources10
Helixi398 – 405Combined sources8
Beta strandi407 – 409Combined sources3
Helixi412 – 434Combined sources23
Helixi436 – 438Combined sources3
Helixi439 – 468Combined sources30
Helixi474 – 477Combined sources4
Helixi480 – 501Combined sources22
Turni504 – 506Combined sources3
Beta strandi511 – 513Combined sources3
Helixi516 – 521Combined sources6
Helixi525 – 529Combined sources5
Helixi532 – 538Combined sources7
Helixi544 – 559Combined sources16
Helixi561 – 563Combined sources3
Beta strandi564 – 566Combined sources3
Helixi569 – 577Combined sources9
Helixi582 – 586Combined sources5
Helixi602 – 607Combined sources6
Helixi645 – 669Combined sources25
Helixi676 – 690Combined sources15
Helixi692 – 695Combined sources4
Helixi700 – 714Combined sources15
Helixi721 – 728Combined sources8
Beta strandi731 – 733Combined sources3
Helixi737 – 740Combined sources4
Beta strandi741 – 743Combined sources3
Beta strandi745 – 747Combined sources3
Beta strandi748 – 750Combined sources3
Helixi752 – 758Combined sources7
Helixi760 – 770Combined sources11
Beta strandi773 – 775Combined sources3
Beta strandi830 – 836Combined sources7
Turni838 – 840Combined sources3
Helixi841 – 853Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AD6X-ray2.30A378-562[»]
1GH6X-ray3.20B379-577[»]
B645-772[»]
1GUXX-ray1.85A372-589[»]
B636-787[»]
1H25X-ray2.50E868-878[»]
1N4MX-ray2.20A/B380-785[»]
1O9KX-ray2.60A/C/E/G372-589[»]
B/D/F/H636-787[»]
1PJMX-ray2.50A858-881[»]
2AZEX-ray2.55C829-874[»]
2QDJX-ray2.00A52-355[»]
2R7GX-ray1.67A/C380-787[»]
3N5UX-ray3.20C870-882[»]
3POMX-ray2.50A/B380-577[»]
A/B643-783[»]
4CRIX-ray2.35C/D802-817[»]
4ELJX-ray2.70A53-787[»]
4ELLX-ray1.98A/B380-787[»]
ProteinModelPortaliP06400.
SMRiP06400.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06400.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni373 – 771Pocket; binds T and E1AAdd BLAST399
Regioni373 – 579Domain AAdd BLAST207
Regioni580 – 639SpacerAdd BLAST60
Regioni640 – 771Domain BAdd BLAST132
Regioni763 – 928Interaction with LIMD11 PublicationAdd BLAST166
Regioni771 – 928Domain C; mediates interaction with E4F11 PublicationAdd BLAST158

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi870 – 876Nuclear localization signalCurated7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi10 – 18Poly-Ala9
Compositional biasi20 – 29Poly-Pro10

Domaini

The Pocket domain binds to the threonine-phosphorylated domain C, thereby preventing interaction with heterodimeric E2F/DP transcription factor complexes.

Sequence similaritiesi

Belongs to the retinoblastoma protein (RB) family.Curated

Phylogenomic databases

eggNOGiKOG1010. Eukaryota.
ENOG410XQF7. LUCA.
GeneTreeiENSGT00530000063235.
HOVERGENiHBG008967.
InParanoidiP06400.
KOiK06618.
OMAiSNGLPEV.
OrthoDBiEOG091G0398.
PhylomeDBiP06400.
TreeFamiTF105568.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR033057. RB1.
IPR002720. RB_A.
IPR002719. RB_B.
IPR015030. RB_C.
IPR028309. RB_fam.
IPR024599. RB_N.
[Graphical view]
PANTHERiPTHR13742. PTHR13742. 1 hit.
PTHR13742:SF21. PTHR13742:SF21. 1 hit.
PfamiPF11934. DUF3452. 1 hit.
PF01858. RB_A. 1 hit.
PF01857. RB_B. 1 hit.
PF08934. Rb_C. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
SM01367. DUF3452. 1 hit.
SM01368. RB_A. 1 hit.
SM01369. Rb_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P06400-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPKTPRKTA ATAAAAAAEP PAPPPPPPPE EDPEQDSGPE DLPLVRLEFE
60 70 80 90 100
ETEEPDFTAL CQKLKIPDHV RERAWLTWEK VSSVDGVLGG YIQKKKELWG
110 120 130 140 150
ICIFIAAVDL DEMSFTFTEL QKNIEISVHK FFNLLKEIDT STKVDNAMSR
160 170 180 190 200
LLKKYDVLFA LFSKLERTCE LIYLTQPSSS ISTEINSALV LKVSWITFLL
210 220 230 240 250
AKGEVLQMED DLVISFQLML CVLDYFIKLS PPMLLKEPYK TAVIPINGSP
260 270 280 290 300
RTPRRGQNRS ARIAKQLEND TRIIEVLCKE HECNIDEVKN VYFKNFIPFM
310 320 330 340 350
NSLGLVTSNG LPEVENLSKR YEEIYLKNKD LDARLFLDHD KTLQTDSIDS
360 370 380 390 400
FETQRTPRKS NLDEEVNVIP PHTPVRTVMN TIQQLMMILN SASDQPSENL
410 420 430 440 450
ISYFNNCTVN PKESILKRVK DIGYIFKEKF AKAVGQGCVE IGSQRYKLGV
460 470 480 490 500
RLYYRVMESM LKSEEERLSI QNFSKLLNDN IFHMSLLACA LEVVMATYSR
510 520 530 540 550
STSQNLDSGT DLSFPWILNV LNLKAFDFYK VIESFIKAEG NLTREMIKHL
560 570 580 590 600
ERCEHRIMES LAWLSDSPLF DLIKQSKDRE GPTDHLESAC PLNLPLQNNH
610 620 630 640 650
TAADMYLSPV RSPKKKGSTT RVNSTANAET QATSAFQTQK PLKSTSLSLF
660 670 680 690 700
YKKVYRLAYL RLNTLCERLL SEHPELEHII WTLFQHTLQN EYELMRDRHL
710 720 730 740 750
DQIMMCSMYG ICKVKNIDLK FKIIVTAYKD LPHAVQETFK RVLIKEEEYD
760 770 780 790 800
SIIVFYNSVF MQRLKTNILQ YASTRPPTLS PIPHIPRSPY KFPSSPLRIP
810 820 830 840 850
GGNIYISPLK SPYKISEGLP TPTKMTPRSR ILVSIGESFG TSEKFQKINQ
860 870 880 890 900
MVCNSDRVLK RSAEGSNPPK PLKKLRFDIE GSDEADGSKH LPGESKFQQK
910 920
LAEMTSTRTR MQKQKMNDSM DTSNKEEK
Length:928
Mass (Da):106,159
Last modified:January 1, 1990 - v2
Checksum:iC8E746111E19CC32
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti500 – 501RS → SN in AAN64133 (Ref. 7) Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00557272E → Q in RB. 1 Publication1
Natural variantiVAR_051909133N → H.Corresponds to variant rs3092900dbSNPEnsembl.1
Natural variantiVAR_005573137E → D in RB; unilateral form. 1 PublicationCorresponds to variant rs3092902dbSNPEnsembl.1
Natural variantiVAR_069376173Y → H.1 Publication1
Natural variantiVAR_005574185I → T in RB. 1 Publication1
Natural variantiVAR_010045310G → E in RB; unknown pathological significance. 1 PublicationCorresponds to variant rs200844292dbSNPEnsembl.1
Natural variantiVAR_010046358R → G in RB. 1 Publication1
Natural variantiVAR_005575358R → Q in RB. Corresponds to variant rs767011440dbSNPEnsembl.1
Natural variantiVAR_019379436Q → K.1 PublicationCorresponds to variant rs4151534dbSNPEnsembl.1
Natural variantiVAR_010048447K → Q in RB. 1 Publication1
Natural variantiVAR_005576457M → R in RB. 1 Publication1
Natural variantiVAR_005577480Missing in RB; mild form. 1 Publication1
Natural variantiVAR_011580500R → G in RB. 1 Publication1
Natural variantiVAR_019380525A → G.1 PublicationCorresponds to variant rs4151539dbSNPEnsembl.1
Natural variantiVAR_010049530K → R in RB. 1 Publication1
Natural variantiVAR_005578549H → Y in RB. 1 Publication1
Natural variantiVAR_005579567S → L in RB. 2 PublicationsCorresponds to variant rs137853292dbSNPEnsembl.1
Natural variantiVAR_051910569L → F.Corresponds to variant rs3092895dbSNPEnsembl.1
Natural variantiVAR_011581616K → E in RB. 1 Publication1
Natural variantiVAR_005580635A → P in RB. 1 Publication1
Natural variantiVAR_005581654V → E in RB. 1 Publication1
Natural variantiVAR_010050657L → P in RB. 1 Publication1
Natural variantiVAR_005582661R → W in RB; mild form. 4 PublicationsCorresponds to variant rs137853294dbSNPEnsembl.1
Natural variantiVAR_005583662L → P in RB. 1 Publication1
Natural variantiVAR_005584673H → P in RB. 1
Natural variantiVAR_005585685Q → P in RB. 1 Publication1
Natural variantiVAR_051911697D → E.Corresponds to variant rs3092903dbSNPEnsembl.1
Natural variantiVAR_005586706C → Y in RB. 1
Natural variantiVAR_005587712C → R in RB. 1 PublicationCorresponds to variant rs137853296dbSNPEnsembl.1
Natural variantiVAR_034442746E → G.Corresponds to variant rs3092905dbSNPEnsembl.1
Natural variantiVAR_005588803N → K in RB. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15400 mRNA. Translation: AAA69807.1. Sequence problems.
M28419 mRNA. Translation: AAA69808.1.
M33647 mRNA. Translation: AAA69806.1.
L41870 mRNA. Translation: AAB59465.1.
M27866
, M27845, M27846, M27847, M27849, M27850, M27851, L35146, M27852, M27853, M27854, M27855, M27856, M27857, M27858, M27859, M27860, L35147, M27862, M27863, M27864, M27865 Genomic DNA. Translation: AAA53484.1.
L41889 Genomic DNA. Translation: AAB59467.1.
L41890 Genomic DNA. Translation: AAA65735.1.
L41891 Genomic DNA. Translation: AAA65736.1.
L41893 Genomic DNA. Translation: AAA65737.1.
L41894 Genomic DNA. Translation: AAA65738.1.
L41895 Genomic DNA. Translation: AAA65739.1.
L41896 Genomic DNA. Translation: AAA65740.1.
L41897 Genomic DNA. Translation: AAA65741.1.
L41898 Genomic DNA. Translation: AAB59471.1.
L41899 Genomic DNA. Translation: AAB59473.1.
L41997 Genomic DNA. Translation: AAB59482.1.
X16439 Genomic DNA. Translation: CAA34462.1.
AF551763 Genomic DNA. Translation: AAN64133.1.
AK291258 mRNA. Translation: BAF83947.1.
AL136960, AL392048 Genomic DNA. Translation: CAH70901.1.
AL392048, AL136960 Genomic DNA. Translation: CAH72243.1.
CH471075 Genomic DNA. Translation: EAX08793.1.
BC039060 mRNA. Translation: AAH39060.1.
BC040540 mRNA. Translation: AAH40540.1.
L11910 Genomic DNA. Translation: AAA53483.1.
CCDSiCCDS31973.1.
PIRiJS0276. RBHU.
RefSeqiNP_000312.2. NM_000321.2.
UniGeneiHs.408528.

Genome annotation databases

EnsembliENST00000267163; ENSP00000267163; ENSG00000139687.
GeneIDi5925.
KEGGihsa:5925.
UCSCiuc001vcb.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

RB1base

RB1 mutation db

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
Wikipedia

Retinoblastoma protein entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15400 mRNA. Translation: AAA69807.1. Sequence problems.
M28419 mRNA. Translation: AAA69808.1.
M33647 mRNA. Translation: AAA69806.1.
L41870 mRNA. Translation: AAB59465.1.
M27866
, M27845, M27846, M27847, M27849, M27850, M27851, L35146, M27852, M27853, M27854, M27855, M27856, M27857, M27858, M27859, M27860, L35147, M27862, M27863, M27864, M27865 Genomic DNA. Translation: AAA53484.1.
L41889 Genomic DNA. Translation: AAB59467.1.
L41890 Genomic DNA. Translation: AAA65735.1.
L41891 Genomic DNA. Translation: AAA65736.1.
L41893 Genomic DNA. Translation: AAA65737.1.
L41894 Genomic DNA. Translation: AAA65738.1.
L41895 Genomic DNA. Translation: AAA65739.1.
L41896 Genomic DNA. Translation: AAA65740.1.
L41897 Genomic DNA. Translation: AAA65741.1.
L41898 Genomic DNA. Translation: AAB59471.1.
L41899 Genomic DNA. Translation: AAB59473.1.
L41997 Genomic DNA. Translation: AAB59482.1.
X16439 Genomic DNA. Translation: CAA34462.1.
AF551763 Genomic DNA. Translation: AAN64133.1.
AK291258 mRNA. Translation: BAF83947.1.
AL136960, AL392048 Genomic DNA. Translation: CAH70901.1.
AL392048, AL136960 Genomic DNA. Translation: CAH72243.1.
CH471075 Genomic DNA. Translation: EAX08793.1.
BC039060 mRNA. Translation: AAH39060.1.
BC040540 mRNA. Translation: AAH40540.1.
L11910 Genomic DNA. Translation: AAA53483.1.
CCDSiCCDS31973.1.
PIRiJS0276. RBHU.
RefSeqiNP_000312.2. NM_000321.2.
UniGeneiHs.408528.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AD6X-ray2.30A378-562[»]
1GH6X-ray3.20B379-577[»]
B645-772[»]
1GUXX-ray1.85A372-589[»]
B636-787[»]
1H25X-ray2.50E868-878[»]
1N4MX-ray2.20A/B380-785[»]
1O9KX-ray2.60A/C/E/G372-589[»]
B/D/F/H636-787[»]
1PJMX-ray2.50A858-881[»]
2AZEX-ray2.55C829-874[»]
2QDJX-ray2.00A52-355[»]
2R7GX-ray1.67A/C380-787[»]
3N5UX-ray3.20C870-882[»]
3POMX-ray2.50A/B380-577[»]
A/B643-783[»]
4CRIX-ray2.35C/D802-817[»]
4ELJX-ray2.70A53-787[»]
4ELLX-ray1.98A/B380-787[»]
ProteinModelPortaliP06400.
SMRiP06400.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111860. 227 interactors.
DIPiDIP-582N.
IntActiP06400. 121 interactors.
MINTiMINT-98847.
STRINGi9606.ENSP00000267163.

Chemistry databases

BindingDBiP06400.
ChEMBLiCHEMBL5288.
DrugBankiDB00030. Insulin Regular.

PTM databases

iPTMnetiP06400.
PhosphoSitePlusiP06400.

Polymorphism and mutation databases

BioMutaiRB1.
DMDMi132164.

Proteomic databases

EPDiP06400.
MaxQBiP06400.
PaxDbiP06400.
PeptideAtlasiP06400.
PRIDEiP06400.

Protocols and materials databases

DNASUi5925.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267163; ENSP00000267163; ENSG00000139687.
GeneIDi5925.
KEGGihsa:5925.
UCSCiuc001vcb.4. human.

Organism-specific databases

CTDi5925.
DisGeNETi5925.
GeneCardsiRB1.
GeneReviewsiRB1.
HGNCiHGNC:9884. RB1.
HPAiCAB000095.
CAB016687.
HPA050082.
MalaCardsiRB1.
MIMi109800. phenotype.
180200. phenotype.
259500. phenotype.
614041. gene.
neXtProtiNX_P06400.
OpenTargetsiENSG00000139687.
Orphaneti357027. Familial retinoblastoma.
1587. Monosomy 13q14.
357034. Unilateral retinoblastoma.
PharmGKBiPA295.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1010. Eukaryota.
ENOG410XQF7. LUCA.
GeneTreeiENSGT00530000063235.
HOVERGENiHBG008967.
InParanoidiP06400.
KOiK06618.
OMAiSNGLPEV.
OrthoDBiEOG091G0398.
PhylomeDBiP06400.
TreeFamiTF105568.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139687-MONOMER.
ReactomeiR-HSA-113501. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
R-HSA-2299718. Condensation of Prophase Chromosomes.
R-HSA-2559584. Formation of Senescence-Associated Heterochromatin Foci (SAHF).
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-69200. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
R-HSA-69202. Cyclin E associated events during G1/S transition.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-69656. Cyclin A:Cdk2-associated events at S phase entry.
SignaLinkiP06400.
SIGNORiP06400.

Miscellaneous databases

ChiTaRSiRB1. human.
EvolutionaryTraceiP06400.
GeneWikiiRetinoblastoma_protein.
GenomeRNAii5925.
PMAP-CutDBP06400.
PROiP06400.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139687.
CleanExiHS_RB1.
ExpressionAtlasiP06400. baseline and differential.
GenevisibleiP06400. HS.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR033057. RB1.
IPR002720. RB_A.
IPR002719. RB_B.
IPR015030. RB_C.
IPR028309. RB_fam.
IPR024599. RB_N.
[Graphical view]
PANTHERiPTHR13742. PTHR13742. 1 hit.
PTHR13742:SF21. PTHR13742:SF21. 1 hit.
PfamiPF11934. DUF3452. 1 hit.
PF01858. RB_A. 1 hit.
PF01857. RB_B. 1 hit.
PF08934. Rb_C. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
SM01367. DUF3452. 1 hit.
SM01368. RB_A. 1 hit.
SM01369. Rb_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiRB_HUMAN
AccessioniPrimary (citable) accession number: P06400
Secondary accession number(s): A8K5E3
, P78499, Q5VW46, Q8IZL4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1990
Last modified: November 30, 2016
This is version 223 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.