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Protein

Retinoblastoma-associated protein

Gene

Rb1

Organism
Rattus norvegicus (Rat)
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.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Repressor

Keywords - Biological processi

Cell cycle, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoblastoma-associated protein
Alternative name(s):
pRb
Short name:
Rb
pp105
Gene namesi
Name:Rb1
Synonyms:Rb-1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3540. Rb1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi772 – 7721S → A: Decreased association with HDAC1; when associated with A-780 and A-787. 1 Publication
Mutagenesisi780 – 7801S → A: Decreased association with HDAC1; when associated with A-772 and A-787. 1 Publication
Mutagenesisi787 – 7871S → A: Decreased association with HDAC1; when associated with A-772 and A-780. 1 Publication

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 920919Retinoblastoma-associated proteinPRO_0000167838Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N,N-dimethylprolineBy similarity
Modified residuei30 – 301PhosphoserineCombined sources
Modified residuei242 – 2421Phosphoserine; by CDK1By similarity
Modified residuei245 – 2451Phosphothreonine; by CDK1By similarity
Modified residuei349 – 3491PhosphothreonineBy similarity
Modified residuei363 – 3631PhosphothreonineCombined sources
Modified residuei366 – 3661PhosphothreonineCombined sources
Modified residuei560 – 5601Phosphoserine; by CDK2By similarity
Modified residuei600 – 6001PhosphoserineBy similarity
Modified residuei604 – 6041Phosphoserine; by CHEK2 and CHEK1By similarity
Modified residuei772 – 7721PhosphoserineSequence analysisBy similarity
Modified residuei780 – 7801PhosphoserineSequence analysis
Modified residuei787 – 7871Phosphoserine1 Publication
Modified residuei799 – 7991PhosphoserineCombined sources
Modified residuei802 – 8021N6-methyllysine; by SMYD2By similarity
Modified residuei803 – 8031Phosphoserine; by CDK1 and CDK3By similarity
Modified residuei813 – 8131Phosphothreonine; by CDK6By similarity
Modified residuei815 – 8151PhosphothreonineBy similarity
Modified residuei818 – 8181Phosphothreonine; by CDK4By similarity
Modified residuei833 – 8331PhosphothreonineBy similarity
Modified residuei847 – 8471PhosphoserineBy similarity
Modified residuei852 – 8521N6-methyllysine; by SMYD2By similarity
Modified residuei865 – 8651N6-acetyllysine; by PCAFBy similarity
Modified residuei866 – 8661N6-acetyllysine; by PCAFBy similarity

Post-translational modificationi

Phosphorylated by CDK6 and CDK4, and subsequently by CDK2 at Ser-560 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. CDK3/cyclin-C-mediated phosphorylation at Ser-799 and Ser-803 is required for G0-G1 transition (By similarity). Dephosphorylated at Ser-787 by calcineruin upon calcium stimulation.By similarity2 Publications
N-terminus is methylated by METTL11A/NTM1. Monomethylation at Lys-802 by SMYD2 enhances phosphorylation at Ser-799 and Ser-803, and promotes cell cycle progression. Monomethylation at Lys-852 by SMYD2 promotes interaction with L3MBTL1 (By similarity).By similarity
Acetylation at Lys-865 and Lys-866 regulates subcellular localization, at least during keratinocytes differentiation.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

PaxDbiP33568.
PRIDEiP33568.

PTM databases

iPTMnetiP33568.
PhosphoSiteiP33568.

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 and TMPO-alpha. May interact with NDC80. Interacts with GRIP1 and UBR4. Interacts with ARID4A and KDM5B. Interacts with E4F1, LIMD1 and USP4. Interacts with PRMT2. Interacts (when methylated at Lys-852) with L3MBTL. Interacts with CHEK2; phosphorylates RB1 (By similarity). Interacts with SMARCA4/BRG1 and HDAC1. Binds to CDK1 and CDK2. P-TEFB complex interacts with RB1; promotes phosphorylation of RB1 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
E2f1O091392EBI-1162932,EBI-1211101
Rbbp9O883504EBI-1162932,EBI-1211014

GO - Molecular functioni

Protein-protein interaction databases

BioGridi246837. 5 interactions.
IntActiP33568. 3 interactions.
STRINGi10116.ENSRNOP00000021752.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni366 – 763398Pocket; binds T and E1ABy similarityAdd
BLAST
Regioni366 – 572207Domain ABy similarityAdd
BLAST
Regioni573 – 63159SpacerBy similarityAdd
BLAST
Regioni632 – 763132Domain BBy similarityAdd
BLAST
Regioni755 – 920166Interaction with LIMD1By similarityAdd
BLAST
Regioni763 – 920158Domain C; mediates interaction with E4F1By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi862 – 8687Nuclear localization signalBy similarity

Sequence similaritiesi

Belongs to the retinoblastoma protein (RB) family.Curated

Phylogenomic databases

eggNOGiKOG1010. Eukaryota.
ENOG410XQF7. LUCA.
HOGENOMiHOG000136539.
HOVERGENiHBG008967.
InParanoidiP33568.
KOiK06618.
OrthoDBiEOG7P5T04.
PhylomeDBiP33568.
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.

P33568-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPKAPRRTA AAEPPPPPPP PPEDDPAQDS DPEELPLIRL EFEKIEEPEF
60 70 80 90 100
IALCQKLKVP DHVRERAWLT WEKVSSVDGI LEGYIQKKKE LWGICIFIAA
110 120 130 140 150
VDLDEMPFTF TELQKSIETS VYKFFDLLKE IDTSTKVDNA VSRLLKKYNV
160 170 180 190 200
LCALYSKLER TCGLIYLTQP SSGLSTEINS MLVLKVSWIT FLLAKGEVVQ
210 220 230 240 250
MEDDLVISFQ LMLCVLDYFI KLSPPALLRE PYKTAATPIN GSPRTPRRGQ
260 270 280 290 300
NRSARIAKQL ESDTRTIEVL CKEHECNVDE VKNVYFKNFI PFISSLGIVS
310 320 330 340 350
SNGLPELESL SKRYEEVYLK SKDLDARLFL DHDKTLQTDT IDSFETERTP
360 370 380 390 400
RKSNPDEEAN MVTPHTPVRT VMNTIQQLMV ILNSASDQPS ENLISYFSNC
410 420 430 440 450
TVNPKENILK RVKDVGHIFK EKFASAVGQG CIDIGAQRYK LGVRLYYRVM
460 470 480 490 500
ESMLKSEEER LSIQNFSKLL NDNIFHMSLL ACALEVVMAT YSRSMLQNLD
510 520 530 540 550
SGTDLSFPWI LNVLNLKAFD FYKVIESFIK VEANLTREMI KHLERCEHRI
560 570 580 590 600
MESLAWLSDS PLFDLIKQSK DGEGPDHLES ACSLSLPLQS NHTAADMYLS
610 620 630 640 650
PIRSPKKRTS TTRVNSAANT ETQAASAFHT QKPLKSTSLS LFYKKVYRLA
660 670 680 690 700
YLRLNTLCAR LLSDHPELEH IIWTLFQHTL ENEYELMKDR HLDQIMMCSM
710 720 730 740 750
YGICKVKNID LKFKIIVTAY KDLPHAAQET FKRVLIREEE FDSIIVFYNS
760 770 780 790 800
VFMQRLKTNI LQYASTRPPT LSPIPHIPRS PYKFSSSPLR IPGGNIYISP
810 820 830 840 850
LKSPYKISEG LPTPTKMTPR SRILVSIGES FGTSEKFQKI NQMVCNSDRV
860 870 880 890 900
LKRSAEGGNP PKPLKKLRFD IEGSDEADGS KHLPAESKFQ QKLAEMTSTR
910 920
TRMQKQKLND SMEISNKEEK
Length:920
Mass (Da):105,025
Last modified:February 9, 2010 - v3
Checksum:i3BA735EA59927301
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti668 – 6681L → P in BAA04958 (PubMed:7665085).Curated
Sequence conflicti798 – 7981I → M in BAA04958 (PubMed:7665085).Curated
Sequence conflicti866 – 8672KL → TW in AAA42090 (PubMed:8441612).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D25233 mRNA. Translation: BAA04958.1.
L07126 mRNA. Translation: AAA42090.1.
PIRiS35544.
RefSeqiNP_058741.1. NM_017045.1.
UniGeneiRn.55115.

Genome annotation databases

GeneIDi24708.
KEGGirno:24708.
UCSCiRGD:3540. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D25233 mRNA. Translation: BAA04958.1.
L07126 mRNA. Translation: AAA42090.1.
PIRiS35544.
RefSeqiNP_058741.1. NM_017045.1.
UniGeneiRn.55115.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246837. 5 interactions.
IntActiP33568. 3 interactions.
STRINGi10116.ENSRNOP00000021752.

PTM databases

iPTMnetiP33568.
PhosphoSiteiP33568.

Proteomic databases

PaxDbiP33568.
PRIDEiP33568.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24708.
KEGGirno:24708.
UCSCiRGD:3540. rat.

Organism-specific databases

CTDi5925.
RGDi3540. Rb1.

Phylogenomic databases

eggNOGiKOG1010. Eukaryota.
ENOG410XQF7. LUCA.
HOGENOMiHOG000136539.
HOVERGENiHBG008967.
InParanoidiP33568.
KOiK06618.
OrthoDBiEOG7P5T04.
PhylomeDBiP33568.
TreeFamiTF105568.

Miscellaneous databases

PROiP33568.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  2. "Isolation and sequence polymorphism of a rat retinoblastoma (RB) cDNA."
    Esumi M., Idutsu T., Kinugasa S., Ohno M., Nakabayashi H., Ikeda T., Shikata T.
    Gene 161:231-235(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-920.
    Strain: Sprague-Dawley.
    Tissue: Liver.
  3. "Cloning and sequence of the rat retinoblastoma (Rb) gene cDNA."
    Roy N.K., Ballesteros A., Garte S.J.
    Nucleic Acids Res. 21:170-170(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 806-920.
    Strain: Sprague-Dawley.
    Tissue: Kidney.
  4. "Cdc2 and Cdk2 kinase activated by transforming growth factor-beta1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells."
    Choi K.S., Eom Y.W., Kang Y., Ha M.J., Rhee H., Yoon J.-W., Kim S.-J.
    J. Biol. Chem. 274:31775-31783(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY CDK1 AND CDK2, INTERACTION WITH CDK1 AND CDK2.
  5. "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.
  6. "A calcium-dependent switch in a CREST-BRG1 complex regulates activity-dependent gene expression."
    Qiu Z., Ghosh A.
    Neuron 60:775-787(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SMARCA4 AND HDAC1, PHOSPHORYLATION AT SER-787, DEPHOSPHORYLATION, MUTAGENESIS OF SER-772; SER-780 AND SER-787.
  7. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30; THR-363; THR-366 AND SER-799, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiRB_RAT
AccessioniPrimary (citable) accession number: P33568
Secondary accession number(s): Q63527
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 9, 2010
Last modified: June 8, 2016
This is version 149 of the entry and version 3 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. 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.