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Protein

Retinoblastoma-associated protein

Gene

Rb1

Organism
Mus musculus (Mouse)
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).By similarity2 Publications

GO - Molecular functioni

  • core promoter binding Source: MGI
  • enzyme binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • phosphoprotein binding Source: MGI
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: MGI

GO - Biological processi

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

Keywords - Molecular functioni

Chromatin regulator, Repressor

Keywords - Biological processi

Cell cycle, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-2299718. Condensation of Prophase Chromosomes.
R-MMU-2559584. Formation of Senescence-Associated Heterochromatin Foci (SAHF).
R-MMU-68949. Orc1 removal from chromatin.
R-MMU-69200. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
R-MMU-69202. Cyclin E associated events during G1/S transition.
R-MMU-69231. Cyclin D associated events in G1.
R-MMU-69656. Cyclin A:Cdk2-associated events at S phase entry.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoblastoma-associated protein
Alternative name(s):
pRb
Short name:
Rb
pp105
Gene namesi
Name:Rb1
Synonyms:Rb-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:97874. Rb1.

Subcellular locationi

GO - Cellular componenti

  • cyclin/CDK positive transcription elongation factor complex Source: Ensembl
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
  • Rb-E2F complex Source: BHF-UCL
  • spindle Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi746I → A: Abolishes the interaction with many chromatin regulators but not that with KMT5B and KMT5C; when associated with A-750 and A-754. 1 Publication1
Mutagenesisi750N → A: Abolishes the interaction with many chromatin regulators but not that with KMT5B and KMT5C; when associated with A-746 and A-754. 1 Publication1
Mutagenesisi754M → A: Abolishes the interaction with many chromatin regulators but not that with KMT5B and KMT5C; when associated with A-746 and A-750. 1 Publication1

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001678372 – 921Retinoblastoma-associated proteinAdd BLAST920

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N,N-dimethylproline; by NTM11 Publication1
Modified residuei31PhosphoserineCombined sources1
Modified residuei243PhosphoserineCombined sources1
Modified residuei246PhosphothreonineCombined sources1
Modified residuei350PhosphothreonineBy similarity1
Modified residuei364PhosphothreonineCombined sources1
Modified residuei367PhosphothreonineCombined sources1
Modified residuei561Phosphoserine; by CDK2By similarity1
Modified residuei601PhosphoserineCombined sources1
Modified residuei605PhosphoserineCombined sources1
Modified residuei617PhosphoserineBy similarity1
Modified residuei773PhosphoserineCombined sources1
Modified residuei781PhosphoserineBy similarity1
Modified residuei788PhosphoserineBy similarity1
Modified residuei800PhosphoserineCombined sources1
Modified residuei803N6-methyllysine; by SMYD2By similarity1
Modified residuei804PhosphoserineCombined sources1
Modified residuei814PhosphothreonineCombined sources1
Modified residuei816PhosphothreonineBy similarity1
Modified residuei819PhosphothreonineCombined sources1
Modified residuei834PhosphothreonineBy similarity1
Modified residuei848PhosphoserineCombined sources1
Modified residuei853N6-methyllysine; by SMYD2By similarity1
Modified residuei866N6-acetyllysine; by PCAFBy similarity1
Modified residuei867N6-acetyllysine; by PCAFBy similarity1

Post-translational modificationi

Phosphorylated by CDK6 and CDK4, and subsequently by CDK2 at Ser-561 in G1, thereby releasing E2F1 which is then able to activate cell growth. Dephosphorylated at the late M phase. Phosphorylation of threonine residues in domain C 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-788 by calcineruin upon calcium stimulation. CDK3/cyclin-C-mediated phosphorylation at Ser-800 and Ser-804 is required for G0-G1 transition (By similarity). Phosphorylated by CDK1 and CDK2 upon TGFB1-mediated apoptosis (By similarity).By similarity
Monomethylation at Lys-803 by SMYD2 enhances phosphorylation at Ser-800 and Ser-804, and promotes cell cycle progression. Monomethylation at Lys-853 by SMYD2 promotes interaction with L3MBTL1 (By similarity). N-terminus is methylated by METTL11A/NTM1.By similarity1 Publication
Acetylation at Lys-866 and Lys-867 regulates subcellular localization, at least during keratinocytes differentiation.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP13405.
MaxQBiP13405.
PaxDbiP13405.
PeptideAtlasiP13405.
PRIDEiP13405.

PTM databases

iPTMnetiP13405.
PhosphoSitePlusiP13405.

Expressioni

Tissue specificityi

Expressed in the cell nuclei of renal tubules, hepathocytes and skeletal muscles. Colocalizes with RB1CC1 in various tissues.1 Publication

Gene expression databases

BgeeiENSMUSG00000022105.
CleanExiMM_RB1.
ExpressionAtlasiP13405. baseline and differential.
GenevisibleiP13405. MM.

Interactioni

Subunit structurei

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, ATAD5, AATF, DNMT1, LIN9, LMNA, KMT5B, KMT5C, PELP1, UHRF2, TMPO-alpha and USP4. 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. Interacts with USP4. Interacts (when methylated at Lys-853) with L3MBTL1. Binds to CDK1 and CDK2. Interacts with CHEK2; phosphorylates RB1 (By similarity). Interacts with PRMT2. Interacts with CEBPA. P-TEFB complex interacts with RB1; promotes phosphorylation of RB1 (By similarity).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CenpfQ155P74EBI-971782,EBI-2211248
DgkzQ80UP32EBI-971782,EBI-971774
Ifi202Q9R0027EBI-971782,EBI-3043899
Pax3P246103EBI-971782,EBI-1208116
Pdx1P529462EBI-971782,EBI-7128945
Smarca4Q3TKT43EBI-971782,EBI-1210244
Vsx2Q614122EBI-971782,EBI-1208174

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • phosphoprotein binding Source: MGI
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: MGI

Protein-protein interaction databases

BioGridi202815. 34 interactors.
DIPiDIP-37637N.
IntActiP13405. 16 interactors.
MINTiMINT-225292.
STRINGi10090.ENSMUSP00000022701.

Structurei

3D structure databases

ProteinModelPortaliP13405.
SMRiP13405.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni367 – 764Pocket; binds T and E1ABy similarityAdd BLAST398
Regioni367 – 573Domain ABy similarityAdd BLAST207
Regioni574 – 632SpacerBy similarityAdd BLAST59
Regioni633 – 764Domain BBy similarityAdd BLAST132
Regioni756 – 921Interaction with LIMD1By similarityAdd BLAST166
Regioni764 – 921Domain; mediates interaction with E4F1By similarityAdd BLAST158

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi863 – 869Nuclear localization signalBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi9 – 12Poly-Ala4
Compositional biasi14 – 22Poly-Pro9

Sequence similaritiesi

Belongs to the retinoblastoma protein (RB) family.Curated

Phylogenomic databases

eggNOGiKOG1010. Eukaryota.
ENOG410XQF7. LUCA.
GeneTreeiENSGT00530000063235.
HOGENOMiHOG000136539.
HOVERGENiHBG008967.
InParanoidiP13405.
KOiK06618.
OMAiSNGLPEV.
OrthoDBiEOG091G0398.
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.

P13405-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPKAPRRAA AAEPPPPPPP PPREDDPAQD SGPEELPLAR LEFEEIEEPE
60 70 80 90 100
FIALCQKLKV PDHVRERAWL TWEKVSSVDG ILEGYIQKKK ELWGICIFIA
110 120 130 140 150
AVDLDEMPFT FTELQKSIET SVYKFFDLLK EIDTSTKVDN AMSRLLKKYN
160 170 180 190 200
VLCALYSKLE RTCELIYLTQ PSSALSTEIN SMLVLKISWI TFLLAKGEVL
210 220 230 240 250
QMEDDLVISF QLMLCVVDYF IKFSPPALLR EPYKTAAIPI NGSPRTPRRG
260 270 280 290 300
QNRSARIAKQ LENDTRIIEV LCKEHECNID EVKNVYFKNF IPFINSLGIV
310 320 330 340 350
SSNGLPEVES LSKRYEEVYL KNKDLDARLF LDHDKTLQTD PIDSFETERT
360 370 380 390 400
PRKNNPDEEA NVVTPHTPVR TVMNTIQQLM VILNSASDQP SENLISYFNN
410 420 430 440 450
CTVNPKENIL KRVKDVGHIF KEKFANAVGQ GCVDIGVQRY KLGVRLYYRV
460 470 480 490 500
MESMLKSEEE RLSIQNFSKL LNDNIFHMSL LACALEVVMA TYSRSTLQHL
510 520 530 540 550
DSGTDLSFPW ILNVLNLKAF DFYKVIESFI KVEANLTREM IKHLERCEHR
560 570 580 590 600
IMESLAWLSD SPLFDLIKQS KDGEGPDNLE PACPLSLPLQ GNHTAADMYL
610 620 630 640 650
SPLRSPKKRT STTRVNSAAN TETQAASAFH TQKPLKSTSL ALFYKKVYRL
660 670 680 690 700
AYLRLNTLCA RLLSDHPELE HIIWTLFQHT LQNEYELMRD RHLDQIMMCS
710 720 730 740 750
MYGICKVKNI DLKFKIIVTA YKDLPHAAQE TFKRVLIREE EFDSIIVFYN
760 770 780 790 800
SVFMQRLKTN ILQYASTRPP TLSPIPHIPR SPYKFSSSPL RIPGGNIYIS
810 820 830 840 850
PLKSPYKISE GLPTPTKMTP RSRILVSIGE SFGTSEKFQK INQMVCNSDR
860 870 880 890 900
VLKRSAEGGN PPKPLKKLRF DIEGADEADG SKHLPAESKF QQKLAEMTST
910 920
RTRMQKQRMN ESKDVSNKEE K
Length:921
Mass (Da):105,367
Last modified:July 27, 2011 - v2
Checksum:iAE81D35A07ADB493
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti867 – 868KL → NV in AAA39964 (PubMed:2671991).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M26391 mRNA. Translation: AAA39964.1.
DQ400415 mRNA. Translation: ABD72475.1.
BC096525 mRNA. Translation: AAH96525.1.
CCDSiCCDS27267.1.
PIRiA33718.
RefSeqiNP_033055.2. NM_009029.2.
UniGeneiMm.273862.

Genome annotation databases

EnsembliENSMUST00000022701; ENSMUSP00000022701; ENSMUSG00000022105.
GeneIDi19645.
KEGGimmu:19645.
UCSCiuc007upp.2. mouse.

Cross-referencesi

Web resourcesi

Wikipedia

Retinoblastoma protein entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M26391 mRNA. Translation: AAA39964.1.
DQ400415 mRNA. Translation: ABD72475.1.
BC096525 mRNA. Translation: AAH96525.1.
CCDSiCCDS27267.1.
PIRiA33718.
RefSeqiNP_033055.2. NM_009029.2.
UniGeneiMm.273862.

3D structure databases

ProteinModelPortaliP13405.
SMRiP13405.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202815. 34 interactors.
DIPiDIP-37637N.
IntActiP13405. 16 interactors.
MINTiMINT-225292.
STRINGi10090.ENSMUSP00000022701.

PTM databases

iPTMnetiP13405.
PhosphoSitePlusiP13405.

Proteomic databases

EPDiP13405.
MaxQBiP13405.
PaxDbiP13405.
PeptideAtlasiP13405.
PRIDEiP13405.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022701; ENSMUSP00000022701; ENSMUSG00000022105.
GeneIDi19645.
KEGGimmu:19645.
UCSCiuc007upp.2. mouse.

Organism-specific databases

CTDi5925.
MGIiMGI:97874. Rb1.

Phylogenomic databases

eggNOGiKOG1010. Eukaryota.
ENOG410XQF7. LUCA.
GeneTreeiENSGT00530000063235.
HOGENOMiHOG000136539.
HOVERGENiHBG008967.
InParanoidiP13405.
KOiK06618.
OMAiSNGLPEV.
OrthoDBiEOG091G0398.
TreeFamiTF105568.

Enzyme and pathway databases

ReactomeiR-MMU-2299718. Condensation of Prophase Chromosomes.
R-MMU-2559584. Formation of Senescence-Associated Heterochromatin Foci (SAHF).
R-MMU-68949. Orc1 removal from chromatin.
R-MMU-69200. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
R-MMU-69202. Cyclin E associated events during G1/S transition.
R-MMU-69231. Cyclin D associated events in G1.
R-MMU-69656. Cyclin A:Cdk2-associated events at S phase entry.

Miscellaneous databases

PROiP13405.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022105.
CleanExiMM_RB1.
ExpressionAtlasiP13405. baseline and differential.
GenevisibleiP13405. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: P13405
Secondary accession number(s): Q4VA62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 179 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.