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P13405 (RB_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Retinoblastoma-associated protein
Alternative name(s):
pRb
Short name=Rb
pp105
Gene names
Name:Rb1
Synonyms:Rb-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length921 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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, SUV420H1 and SUV420H2, 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. Ref.8 Ref.11

Subunit structure

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, SUV420H1, SUV420H2, 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. Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11

Subcellular location

Nucleus.

Tissue specificity

Expressed in the cell nuclei of renal tubules, hepathocytes and skeletal muscles. Colocalizes with RB1CC1 in various tissues. Ref.7

Post-translational modification

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.

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. Ref.12

Acetylation at Lys-866 and Lys-867 regulates subcellular localization, at least during keratinocytes differentiation By similarity.

Sequence similarities

Belongs to the retinoblastoma protein (RB) family.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
   Cellular componentNucleus
   DiseaseTumor suppressor
   LigandDNA-binding
   Molecular functionChromatin regulator
Repressor
   PTMAcetylation
Methylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 15831459. Source: MGI

Ras protein signal transduction

Inferred from electronic annotation. Source: Ensembl

cell cycle arrest

Inferred from mutant phenotype PubMed 15831459. Source: MGI

cell division

Inferred from mutant phenotype PubMed 15843406. Source: MGI

cell morphogenesis involved in neuron differentiation

Inferred from mutant phenotype PubMed 7958874. Source: MGI

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

digestive tract development

Inferred from mutant phenotype PubMed 17257418. Source: MGI

enucleate erythrocyte differentiation

Inferred from genetic interaction PubMed 15616565. Source: MGI

glial cell apoptotic process

Inferred from mutant phenotype PubMed 11549719. Source: MGI

hepatocyte apoptotic process

Inferred from mutant phenotype PubMed 11549719. Source: MGI

maintenance of mitotic sister chromatid cohesion

Inferred from electronic annotation. Source: Ensembl

myoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of G1/S transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 7958874. Source: MGI

negative regulation of cell cycle

Inferred from mutant phenotype PubMed 12853964. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 15843406. Source: MGI

negative regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 17257418. Source: MGI

negative regulation of protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of smoothened signaling pathway

Inferred from mutant phenotype PubMed 17257418. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 20224733. Source: BHF-UCL

negative regulation of transcription involved in G1/S transition of mitotic cell cycle

Inferred from genetic interaction PubMed 20224733. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11331592. Source: MGI

neuron apoptotic process

Inferred from mutant phenotype PubMed 11549719PubMed 7958874. Source: MGI

neuron differentiation

Inferred from mutant phenotype PubMed 7958874. Source: MGI

neuron maturation

Inferred from mutant phenotype PubMed 7958874. Source: MGI

neuron projection development

Inferred from mutant phenotype PubMed 7958874. Source: MGI

positive regulation of macrophage differentiation

Inferred from genetic interaction PubMed 15616565. Source: MGI

positive regulation of mitotic metaphase/anaphase transition

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15701640. Source: MGI

protein localization to chromosome, centromeric region

Inferred from electronic annotation. Source: Ensembl

regulation of cell cycle

Inferred from mutant phenotype PubMed 15898111. Source: MGI

regulation of cohesin localization to chromatin

Inferred from electronic annotation. Source: Ensembl

regulation of lipid kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

sister chromatid biorientation

Inferred from electronic annotation. Source: Ensembl

skeletal muscle cell differentiation

Inferred from mutant phenotype PubMed 22147266. Source: MGI

striated muscle cell differentiation

Inferred from genetic interaction PubMed 15542848. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from sequence or structural similarity. Source: UniProtKB

Rb-E2F complex

Inferred from direct assay PubMed 20224733. Source: BHF-UCL

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

spindle

Inferred from direct assay PubMed 15509711. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 10082561. Source: MGI

   Molecular_functionRNA polymerase II activating transcription factor binding

Inferred from physical interaction PubMed 20224733. Source: BHF-UCL

core promoter binding

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction Ref.10. Source: UniProtKB

kinase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.6PubMed 14555653. Source: UniProtKB

transcription factor binding

Inferred from physical interaction PubMed 9178770. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.12
Chain2 – 921920Retinoblastoma-associated protein
PRO_0000167837

Regions

Region367 – 764398Pocket; binds T and E1A By similarity
Region367 – 573207Domain A By similarity
Region574 – 63259Spacer By similarity
Region633 – 764132Domain B By similarity
Region756 – 921166Interaction with LIMD1 By similarity
Region764 – 921158Domain; mediates interaction with E4F1 By similarity
Motif863 – 8697Nuclear localization signal By similarity
Compositional bias9 – 124Poly-Ala
Compositional bias14 – 229Poly-Pro

Amino acid modifications

Modified residue21N,N-dimethylproline; by NTM1 Ref.12
Modified residue311Phosphoserine By similarity
Modified residue2431Phosphoserine; by CDK1 By similarity
Modified residue2461Phosphothreonine; by CDK1 By similarity
Modified residue3501Phosphothreonine By similarity
Modified residue3671Phosphothreonine; by CDK1 By similarity
Modified residue5611Phosphoserine; by CDK2 By similarity
Modified residue6051Phosphoserine; by CHEK2 and CHEK1 By similarity
Modified residue7881Phosphoserine By similarity
Modified residue8001Phosphoserine; by CDK1 and CDK3 By similarity
Modified residue8031N6-methyllysine; by SMYD2 By similarity
Modified residue8041Phosphoserine; by CDK1 and CDK3 By similarity
Modified residue8141Phosphothreonine; by CDK6 By similarity
Modified residue8161Phosphothreonine By similarity
Modified residue8191Phosphothreonine; by CDK4
Modified residue8341Phosphothreonine By similarity
Modified residue8531N6-methyllysine; by SMYD2 By similarity
Modified residue8661N6-acetyllysine; by PCAF By similarity
Modified residue8671N6-acetyllysine; by PCAF By similarity

Experimental info

Mutagenesis7461I → A: Abolishes the interaction with many chromatin regulators but not that with SUV420H1 and SUV420H2; when associated with A-750 and A-754. Ref.11
Mutagenesis7501N → A: Abolishes the interaction with many chromatin regulators but not that with SUV420H1 and SUV420H2; when associated with A-746 and A-754. Ref.11
Mutagenesis7541M → A: Abolishes the interaction with many chromatin regulators but not that with SUV420H1 and SUV420H2; when associated with A-746 and A-750. Ref.11
Sequence conflict867 – 8682KL → NV in AAA39964. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P13405 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: AE81D35A07ADB493

FASTA921105,367
        10         20         30         40         50         60 
MPPKAPRRAA AAEPPPPPPP PPREDDPAQD SGPEELPLAR LEFEEIEEPE FIALCQKLKV 

        70         80         90        100        110        120 
PDHVRERAWL TWEKVSSVDG ILEGYIQKKK ELWGICIFIA AVDLDEMPFT FTELQKSIET 

       130        140        150        160        170        180 
SVYKFFDLLK EIDTSTKVDN AMSRLLKKYN VLCALYSKLE RTCELIYLTQ PSSALSTEIN 

       190        200        210        220        230        240 
SMLVLKISWI TFLLAKGEVL QMEDDLVISF QLMLCVVDYF IKFSPPALLR EPYKTAAIPI 

       250        260        270        280        290        300 
NGSPRTPRRG QNRSARIAKQ LENDTRIIEV LCKEHECNID EVKNVYFKNF IPFINSLGIV 

       310        320        330        340        350        360 
SSNGLPEVES LSKRYEEVYL KNKDLDARLF LDHDKTLQTD PIDSFETERT PRKNNPDEEA 

       370        380        390        400        410        420 
NVVTPHTPVR TVMNTIQQLM VILNSASDQP SENLISYFNN CTVNPKENIL KRVKDVGHIF 

       430        440        450        460        470        480 
KEKFANAVGQ GCVDIGVQRY KLGVRLYYRV MESMLKSEEE RLSIQNFSKL LNDNIFHMSL 

       490        500        510        520        530        540 
LACALEVVMA TYSRSTLQHL DSGTDLSFPW ILNVLNLKAF DFYKVIESFI KVEANLTREM 

       550        560        570        580        590        600 
IKHLERCEHR IMESLAWLSD SPLFDLIKQS KDGEGPDNLE PACPLSLPLQ GNHTAADMYL 

       610        620        630        640        650        660 
SPLRSPKKRT STTRVNSAAN TETQAASAFH TQKPLKSTSL ALFYKKVYRL AYLRLNTLCA 

       670        680        690        700        710        720 
RLLSDHPELE HIIWTLFQHT LQNEYELMRD RHLDQIMMCS MYGICKVKNI DLKFKIIVTA 

       730        740        750        760        770        780 
YKDLPHAAQE TFKRVLIREE EFDSIIVFYN SVFMQRLKTN ILQYASTRPP TLSPIPHIPR 

       790        800        810        820        830        840 
SPYKFSSSPL RIPGGNIYIS PLKSPYKISE GLPTPTKMTP RSRILVSIGE SFGTSEKFQK 

       850        860        870        880        890        900 
INQMVCNSDR VLKRSAEGGN PPKPLKKLRF DIEGADEADG SKHLPAESKF QQKLAEMTST 

       910        920 
RTRMQKQRMN ESKDVSNKEE K 

« Hide

References

« Hide 'large scale' references
[1]"Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein."
Bernards R., Schackleford G.M., Gerber M.R., Horowitz J.M., Friend S.H., Schartl M., Bogenmann E., Rapaport J., McGee T., Dryja T.P., Weinberg R.A.
Proc. Natl. Acad. Sci. U.S.A. 86:6474-6478(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Sequencing of the full-length cDNA sequence of the murine retinoblastoma gene."
Wu J., Liao J.D.
Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[4]"DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters."
Robertson K.D., Ait-Si-Ali S., Yokochi T., Wade P.A., Jones P.L., Wolffe A.P.
Nat. Genet. 25:338-342(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNMT1.
[5]"pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120E4F."
Fajas L., Paul C., Zugasti O., Le Cam L., Polanowska J., Fabbrizio E., Medema R., Vignais M.-L., Sardet C.
Proc. Natl. Acad. Sci. U.S.A. 97:7738-7743(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH E4F1.
[6]"Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130."
Blanchette P., Gilchrist C.A., Baker R.T., Gray D.A.
Oncogene 20:5533-5537(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP4.
[7]"Isolation, characterization and mapping of the mouse and human RB1CC1 genes."
Chano T., Ikegawa S., Saito-Ohara F., Inazawa J., Mabuchi A., Saeki Y., Okabe H.
Gene 291:29-34(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, COLOCALIZATION WITH RB1CC1.
Strain: C57BL/6.
Tissue: Skeletal muscle.
[8]"Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin."
Gonzalo S., Garcia-Cao M., Fraga M.F., Schotta G., Peters A.H.F.M., Cotter S.E., Eguia R., Dean D.C., Esteller M., Jenuwein T., Blasco M.A.
Nat. Cell Biol. 7:420-428(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SUV420H1 AND SUV420H2.
[9]"Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis."
Ishii H., Inageta T., Mimori K., Saito T., Sasaki H., Isobe M., Mori M., Croce C.M., Huebner K., Ozawa K., Furukawa Y.
Proc. Natl. Acad. Sci. U.S.A. 102:9655-9660(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATAD5.
[10]"The arginine methyltransferase PRMT2 binds RB and regulates E2F function."
Yoshimoto T., Boehm M., Olive M., Crook M.F., San H., Langenickel T., Nabel E.G.
Exp. Cell Res. 312:2040-2053(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRMT2.
[11]"The retinoblastoma protein regulates pericentric heterochromatin."
Isaac C.E., Francis S.M., Martens A.L., Julian L.M., Seifried L.A., Erdmann N., Binne U.K., Harrington L., Sicinski P., Berube N.G., Dyson N.J., Dick F.A.
Mol. Cell. Biol. 26:3659-3671(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SUV420H1 AND SUV420H2, MUTAGENESIS OF ILE-746; ASN-750 AND MET-754.
[12]"NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein."
Tooley C.E., Petkowski J.J., Muratore-Schroeder T.L., Balsbaugh J.L., Shabanowitz J., Sabat M., Minor W., Hunt D.F., Macara I.G.
Nature 466:1125-1128(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF INITIATOR METHIONINE, METHYLATION AT PRO-2.
+Additional computationally mapped references.

Web resources

Wikipedia

Retinoblastoma protein entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M26391 mRNA. Translation: AAA39964.1.
DQ400415 mRNA. Translation: ABD72475.1.
BC096525 mRNA. Translation: AAH96525.1.
CCDSCCDS27267.1.
PIRA33718.
RefSeqNP_033055.2. NM_009029.2.
UniGeneMm.273862.

3D structure databases

ProteinModelPortalP13405.
SMRP13405. Positions 47-779, 822-865.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202815. 37 interactions.
DIPDIP-37637N.
IntActP13405. 16 interactions.
MINTMINT-225292.

PTM databases

PhosphoSiteP13405.

Proteomic databases

PaxDbP13405.
PRIDEP13405.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022701; ENSMUSP00000022701; ENSMUSG00000022105.
GeneID19645.
KEGGmmu:19645.
UCSCuc007upp.2. mouse.

Organism-specific databases

CTD5925.
MGIMGI:97874. Rb1.

Phylogenomic databases

eggNOGNOG296920.
GeneTreeENSGT00530000063235.
HOGENOMHOG000136539.
HOVERGENHBG008967.
InParanoidQ4VA62.
KOK06618.
OMATNILQYA.
OrthoDBEOG7P5T04.
TreeFamTF105568.

Gene expression databases

ArrayExpressP13405.
BgeeP13405.
CleanExMM_RB1.
GenevestigatorP13405.

Family and domain databases

Gene3D1.10.472.10. 2 hits.
InterProIPR013763. Cyclin-like.
IPR002720. RB_A.
IPR002719. RB_B.
IPR015030. RB_C.
IPR028309. RB_fam.
IPR024599. RB_N.
[Graphical view]
PANTHERPTHR13742. PTHR13742. 1 hit.
PfamPF11934. DUF3452. 1 hit.
PF01858. RB_A. 1 hit.
PF01857. RB_B. 1 hit.
PF08934. Rb_C. 1 hit.
[Graphical view]
SMARTSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMSSF47954. SSF47954. 2 hits.
ProtoNetSearch...

Other

NextBio296890.
PROP13405.
SOURCESearch...

Entry information

Entry nameRB_MOUSE
AccessionPrimary (citable) accession number: P13405
Secondary accession number(s): Q4VA62
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

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