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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)DescriptionActionsGraphical viewLength
Mutagenesisi772S → A: Decreased association with HDAC1; when associated with A-780 and A-787. 1 Publication1
Mutagenesisi780S → A: Decreased association with HDAC1; when associated with A-772 and A-787. 1 Publication1
Mutagenesisi787S → A: Decreased association with HDAC1; when associated with A-772 and A-780. 1 Publication1

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001678382 – 920Retinoblastoma-associated proteinAdd BLAST919

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N,N-dimethylprolineBy similarity1
Modified residuei30PhosphoserineCombined sources1
Modified residuei242Phosphoserine; by CDK1By similarity1
Modified residuei245Phosphothreonine; by CDK1By similarity1
Modified residuei349PhosphothreonineBy similarity1
Modified residuei363PhosphothreonineCombined sources1
Modified residuei366PhosphothreonineCombined sources1
Modified residuei560Phosphoserine; by CDK2By similarity1
Modified residuei600PhosphoserineBy similarity1
Modified residuei604Phosphoserine; by CHEK2 and CHEK1By similarity1
Modified residuei616PhosphoserineBy similarity1
Modified residuei772PhosphoserineSequence analysisBy similarity1
Modified residuei780PhosphoserineSequence analysisBy similarity1
Modified residuei787Phosphoserine1 Publication1
Modified residuei799PhosphoserineCombined sources1
Modified residuei802N6-methyllysine; by SMYD2By similarity1
Modified residuei803Phosphoserine; by CDK1 and CDK3By similarity1
Modified residuei813Phosphothreonine; by CDK6By similarity1
Modified residuei815PhosphothreonineBy similarity1
Modified residuei818Phosphothreonine; by CDK4By similarity1
Modified residuei833PhosphothreonineBy similarity1
Modified residuei847PhosphoserineBy similarity1
Modified residuei852N6-methyllysine; by SMYD2By similarity1
Modified residuei865N6-acetyllysine; by PCAFBy similarity1
Modified residuei866N6-acetyllysine; by PCAFBy similarity1

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.
PhosphoSitePlusiP33568.

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 interactors.
IntActiP33568. 3 interactors.
STRINGi10116.ENSRNOP00000021752.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni366 – 763Pocket; binds T and E1ABy similarityAdd BLAST398
Regioni366 – 572Domain ABy similarityAdd BLAST207
Regioni573 – 631SpacerBy similarityAdd BLAST59
Regioni632 – 763Domain BBy similarityAdd BLAST132
Regioni755 – 920Interaction with LIMD1By similarityAdd BLAST166
Regioni763 – 920Domain C; mediates interaction with E4F1By similarityAdd BLAST158

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi862 – 868Nuclear localization signalBy similarity7

Sequence similaritiesi

Belongs to the retinoblastoma protein (RB) family.Curated

Phylogenomic databases

eggNOGiKOG1010. Eukaryota.
ENOG410XQF7. LUCA.
HOGENOMiHOG000136539.
HOVERGENiHBG008967.
InParanoidiP33568.
KOiK06618.
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)DescriptionActionsGraphical viewLength
Sequence conflicti668L → P in BAA04958 (PubMed:7665085).Curated1
Sequence conflicti798I → M in BAA04958 (PubMed:7665085).Curated1
Sequence conflicti866 – 867KL → TW in AAA42090 (PubMed:8441612).Curated2

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 interactors.
IntActiP33568. 3 interactors.
STRINGi10116.ENSRNOP00000021752.

PTM databases

iPTMnetiP33568.
PhosphoSitePlusiP33568.

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.
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...

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: November 2, 2016
This is version 153 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.