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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
  • identical protein binding Source: IntAct
  • 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 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 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
  • 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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti72 – 721E → Q in RB. 1 Publication
VAR_005572
Natural varianti137 – 1371E → D in RB; unilateral form. 1 Publication
Corresponds to variant rs3092902 [ dbSNP | Ensembl ].
VAR_005573
Natural varianti185 – 1851I → T in RB. 1 Publication
VAR_005574
Natural varianti310 – 3101G → E in RB; unknown pathological significance. 1 Publication
Corresponds to variant rs200844292 [ dbSNP | Ensembl ].
VAR_010045
Natural varianti358 – 3581R → G in RB. 1 Publication
VAR_010046
Natural varianti358 – 3581R → Q in RB.
Corresponds to variant rs767011440 [ dbSNP | Ensembl ].
VAR_005575
Natural varianti447 – 4471K → Q in RB. 1 Publication
VAR_010048
Natural varianti457 – 4571M → R in RB. 1 Publication
VAR_005576
Natural varianti480 – 4801Missing in RB; mild form. 1 Publication
VAR_005577
Natural varianti500 – 5001R → G in RB. 1 Publication
VAR_011580
Natural varianti530 – 5301K → R in RB. 1 Publication
VAR_010049
Natural varianti549 – 5491H → Y in RB. 1 Publication
VAR_005578
Natural varianti567 – 5671S → L in RB. 2 Publications
Corresponds to variant rs137853292 [ dbSNP | Ensembl ].
VAR_005579
Natural varianti616 – 6161K → E in RB. 1 Publication
VAR_011581
Natural varianti635 – 6351A → P in RB. 1 Publication
VAR_005580
Natural varianti654 – 6541V → E in RB. 1 Publication
VAR_005581
Natural varianti657 – 6571L → P in RB. 1 Publication
VAR_010050
Natural varianti661 – 6611R → W in RB; mild form. 4 Publications
Corresponds to variant rs137853294 [ dbSNP | Ensembl ].
VAR_005582
Natural varianti662 – 6621L → P in RB. 1 Publication
VAR_005583
Natural varianti673 – 6731H → P in RB.
VAR_005584
Natural varianti685 – 6851Q → P in RB. 1 Publication
VAR_005585
Natural varianti706 – 7061C → Y in RB.
VAR_005586
Natural varianti712 – 7121C → R in RB. 1 Publication
Corresponds to variant rs137853296 [ dbSNP | Ensembl ].
VAR_005587
Natural varianti803 – 8031N → K in RB. 1 Publication
VAR_005588
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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi821 – 8211T → A: Abolishes interaction with Pocket domain; when associated with A-826. 1 Publication
Mutagenesisi826 – 8261T → A: Abolishes interaction with Pocket domain; when associated with A-821. 1 Publication
Mutagenesisi860 – 8601K → R: Abolishes monomethylation by SMYD2 and subsequent interaction with L3MBTL1. 1 Publication
Mutagenesisi870 – 8701K → R: Does not affect the ability to be methylated by SMYD2; when associated with 873-R-R-874. 1 Publication
Mutagenesisi873 – 8742KK → R: Does not affect the ability to be methylated by SMYD2; when associated with 873-R-R-874. 2 Publications
Mutagenesisi873 – 8742KK → RR: Does not alter Rb localization in cycling cells, but mislocalizes to the cytoplasm during keratinocytes differentiation. 2 Publications

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL5288.
DrugBankiDB00030. Insulin Regular.

Polymorphism and mutation databases

BioMutaiRB1.
DMDMi132164.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 928927Retinoblastoma-associated proteinPRO_0000167836Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N,N-dimethylprolineBy similarity
Modified residuei37 – 371PhosphoserineCombined sources
Modified residuei249 – 2491Phosphoserine; by CDK1Combined sources1 Publication
Modified residuei252 – 2521Phosphothreonine; by CDK1Combined sources1 Publication
Modified residuei356 – 3561PhosphothreonineCombined sources
Modified residuei373 – 3731Phosphothreonine; by CDK1Combined sources1 Publication
Modified residuei567 – 5671Phosphoserine; by CDK21 Publication
Modified residuei608 – 6081PhosphoserineBy similarity
Modified residuei612 – 6121Phosphoserine; by CHEK2 and CHEK1Combined sources1 Publication
Modified residuei624 – 6241PhosphoserineCombined sources
Modified residuei780 – 7801PhosphoserineCombined sources
Modified residuei788 – 7881PhosphoserineCombined sources
Modified residuei795 – 7951PhosphoserineCombined sources
Modified residuei807 – 8071Phosphoserine; by CDK1 and CDK3Combined sources2 Publications
Modified residuei810 – 8101N6-methyllysine; by SMYD21 Publication
Modified residuei811 – 8111Phosphoserine; by CDK1 and CDK3Combined sources2 Publications
Modified residuei821 – 8211Phosphothreonine; by CDK6Combined sources2 Publications
Modified residuei823 – 8231PhosphothreonineCombined sources
Modified residuei826 – 8261Phosphothreonine; by CDK4Combined sources2 Publications
Modified residuei841 – 8411PhosphothreonineCombined sources
Modified residuei855 – 8551PhosphoserineCombined sources
Modified residuei860 – 8601N6-methyllysine; by SMYD21 Publication
Modified residuei873 – 8731N6-acetyllysine; by PCAF1 Publication
Modified residuei874 – 8741N6-acetyllysine; by PCAF1 Publication

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.
PhosphoSiteiP06400.

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.
P032558EBI-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
  • identical protein binding Source: IntAct
  • 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 interactions.
DIPiDIP-582N.
IntActiP06400. 121 interactions.
MINTiMINT-98847.
STRINGi9606.ENSP00000267163.

Chemistry

BindingDBiP06400.

Structurei

Secondary structure

1
928
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi55 – 639Combined sources
Helixi68 – 8215Combined sources
Helixi95 – 11016Combined sources
Helixi117 – 1248Combined sources
Helixi128 – 1358Combined sources
Helixi142 – 17231Combined sources
Beta strandi180 – 1823Combined sources
Helixi188 – 20417Combined sources
Beta strandi207 – 2093Combined sources
Helixi212 – 22817Combined sources
Helixi232 – 2343Combined sources
Turni237 – 2404Combined sources
Helixi241 – 2433Combined sources
Helixi272 – 28110Combined sources
Helixi285 – 29410Combined sources
Helixi296 – 2994Combined sources
Helixi302 – 3065Combined sources
Helixi314 – 32815Combined sources
Helixi333 – 3386Combined sources
Helixi341 – 3433Combined sources
Helixi347 – 3537Combined sources
Helixi382 – 39110Combined sources
Helixi398 – 4058Combined sources
Beta strandi407 – 4093Combined sources
Helixi412 – 43423Combined sources
Helixi436 – 4383Combined sources
Helixi439 – 46830Combined sources
Helixi474 – 4774Combined sources
Helixi480 – 50122Combined sources
Turni504 – 5063Combined sources
Beta strandi511 – 5133Combined sources
Helixi516 – 5216Combined sources
Helixi525 – 5295Combined sources
Helixi532 – 5387Combined sources
Helixi544 – 55916Combined sources
Helixi561 – 5633Combined sources
Beta strandi564 – 5663Combined sources
Helixi569 – 5779Combined sources
Helixi582 – 5865Combined sources
Helixi602 – 6076Combined sources
Helixi645 – 66925Combined sources
Helixi676 – 69015Combined sources
Helixi692 – 6954Combined sources
Helixi700 – 71415Combined sources
Helixi721 – 7288Combined sources
Beta strandi731 – 7333Combined sources
Helixi737 – 7404Combined sources
Beta strandi741 – 7433Combined sources
Beta strandi745 – 7473Combined sources
Beta strandi748 – 7503Combined sources
Helixi752 – 7587Combined sources
Helixi760 – 77011Combined sources
Beta strandi773 – 7753Combined sources
Beta strandi830 – 8367Combined sources
Turni838 – 8403Combined sources
Helixi841 – 85313Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 53-786, 829-872.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06400.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni373 – 771399Pocket; binds T and E1AAdd
BLAST
Regioni373 – 579207Domain AAdd
BLAST
Regioni580 – 63960SpacerAdd
BLAST
Regioni640 – 771132Domain BAdd
BLAST
Regioni763 – 928166Interaction with LIMD1Add
BLAST
Regioni771 – 928158Domain C; mediates interaction with E4F1Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi870 – 8767Nuclear localization signalCurated

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi10 – 189Poly-Ala
Compositional biasi20 – 2910Poly-Pro

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

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        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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti500 – 5012RS → SN in AAN64133 (Ref. 7) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti72 – 721E → Q in RB. 1 Publication
VAR_005572
Natural varianti133 – 1331N → H.
Corresponds to variant rs3092900 [ dbSNP | Ensembl ].
VAR_051909
Natural varianti137 – 1371E → D in RB; unilateral form. 1 Publication
Corresponds to variant rs3092902 [ dbSNP | Ensembl ].
VAR_005573
Natural varianti173 – 1731Y → H.1 Publication
VAR_069376
Natural varianti185 – 1851I → T in RB. 1 Publication
VAR_005574
Natural varianti310 – 3101G → E in RB; unknown pathological significance. 1 Publication
Corresponds to variant rs200844292 [ dbSNP | Ensembl ].
VAR_010045
Natural varianti358 – 3581R → G in RB. 1 Publication
VAR_010046
Natural varianti358 – 3581R → Q in RB.
Corresponds to variant rs767011440 [ dbSNP | Ensembl ].
VAR_005575
Natural varianti436 – 4361Q → K.1 Publication
Corresponds to variant rs4151534 [ dbSNP | Ensembl ].
VAR_019379
Natural varianti447 – 4471K → Q in RB. 1 Publication
VAR_010048
Natural varianti457 – 4571M → R in RB. 1 Publication
VAR_005576
Natural varianti480 – 4801Missing in RB; mild form. 1 Publication
VAR_005577
Natural varianti500 – 5001R → G in RB. 1 Publication
VAR_011580
Natural varianti525 – 5251A → G.1 Publication
Corresponds to variant rs4151539 [ dbSNP | Ensembl ].
VAR_019380
Natural varianti530 – 5301K → R in RB. 1 Publication
VAR_010049
Natural varianti549 – 5491H → Y in RB. 1 Publication
VAR_005578
Natural varianti567 – 5671S → L in RB. 2 Publications
Corresponds to variant rs137853292 [ dbSNP | Ensembl ].
VAR_005579
Natural varianti569 – 5691L → F.
Corresponds to variant rs3092895 [ dbSNP | Ensembl ].
VAR_051910
Natural varianti616 – 6161K → E in RB. 1 Publication
VAR_011581
Natural varianti635 – 6351A → P in RB. 1 Publication
VAR_005580
Natural varianti654 – 6541V → E in RB. 1 Publication
VAR_005581
Natural varianti657 – 6571L → P in RB. 1 Publication
VAR_010050
Natural varianti661 – 6611R → W in RB; mild form. 4 Publications
Corresponds to variant rs137853294 [ dbSNP | Ensembl ].
VAR_005582
Natural varianti662 – 6621L → P in RB. 1 Publication
VAR_005583
Natural varianti673 – 6731H → P in RB.
VAR_005584
Natural varianti685 – 6851Q → P in RB. 1 Publication
VAR_005585
Natural varianti697 – 6971D → E.
Corresponds to variant rs3092903 [ dbSNP | Ensembl ].
VAR_051911
Natural varianti706 – 7061C → Y in RB.
VAR_005586
Natural varianti712 – 7121C → R in RB. 1 Publication
Corresponds to variant rs137853296 [ dbSNP | Ensembl ].
VAR_005587
Natural varianti746 – 7461E → G.
Corresponds to variant rs3092905 [ dbSNP | Ensembl ].
VAR_034442
Natural varianti803 – 8031N → K in RB. 1 Publication
VAR_005588

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
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. Positions 53-786, 829-872.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

BindingDBiP06400.
ChEMBLiCHEMBL5288.
DrugBankiDB00030. Insulin Regular.

PTM databases

iPTMnetiP06400.
PhosphoSiteiP06400.

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.
GeneCardsiRB1.
GeneReviewsiRB1.
HGNCiHGNC:9884. RB1.
HPAiCAB000095.
CAB016687.
HPA050082.
MalaCardsiRB1.
MIMi109800. phenotype.
180200. phenotype.
259500. phenotype.
614041. gene.
neXtProtiNX_P06400.
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

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: September 7, 2016
This is version 220 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.