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Protein

Retinoblastoma-like protein 1

Gene

RBL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Key regulator of entry into cell division. 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 KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. Forms a complex with adenovirus E1A and with SV40 large T antigen. May bind and modulate functionally certain cellular proteins with which T and E1A compete for pocket binding. May act as a tumor suppressor.

GO - Molecular functioni

  • promoter-specific chromatin binding Source: MGI
  • transcription factor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Repressor
Biological processCell cycle, Host-virus interaction, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133 G0 and Early G1
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-69231 Cyclin D associated events in G1
SIGNORiP28749

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoblastoma-like protein 1
Alternative name(s):
107 kDa retinoblastoma-associated protein
Short name:
p107
pRb1
Gene namesi
Name:RBL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000080839.11
HGNCiHGNC:9893 RBL1
MIMi116957 gene
neXtProtiNX_P28749

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi640S → A: Strongly reduces phosphorylation by CDK2 and CDK4. 1 Publication1
Mutagenesisi643S → R: No effect on S-640 phosphorylation, but strongly increases S-640 phosphorylation; when associated with 657-A--A-660. 1 Publication1
Mutagenesisi650S → A: No effect on phosphorylation by CDK2. 1 Publication1
Mutagenesisi657 – 660KRRL → AAAA: Reduces S-640 phosphorylation by CDK2 and CDK4. 1 Publication4

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi5933
OpenTargetsiENSG00000080839
PharmGKBiPA34257

Polymorphism and mutation databases

DMDMi90103515

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001678391 – 1068Retinoblastoma-like protein 1Add BLAST1068

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei332Phosphothreonine; by CDK2Combined sources1 Publication1
Modified residuei369Phosphothreonine; by CDK4Combined sources2 Publications1
Modified residuei385Phosphothreonine; by CDK2Combined sources1 Publication1
Modified residuei640Phosphoserine; by CDK2 and CDK4Combined sources1 Publication1
Modified residuei650Phosphoserine1 Publication1
Modified residuei749PhosphoserineCombined sources1
Modified residuei762Phosphoserine; by CDK2Combined sources1 Publication1
Modified residuei964Phosphoserine; by CDK2 and CDK41 Publication1
Modified residuei975Phosphoserine; by CDK2 and CDK41 Publication1
Modified residuei988Phosphoserine; by CDK2Combined sources1 Publication1
Modified residuei997Phosphothreonine; by CDK21 Publication1
Modified residuei1009Phosphoserine; by CDK21 Publication1
Modified residuei1041PhosphoserineCombined sources1

Post-translational modificationi

Exists in both phosphorylated and unphosphorylated forms, and T, but not E1A, binds only to the unphosphorylated form. Cell-cycle arrest properties are inactivated by phosphorylation on Thr-332, Ser-640, Ser-964 and Ser-975 by CDK4.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP28749
MaxQBiP28749
PaxDbiP28749
PeptideAtlasiP28749
PRIDEiP28749
ProteomicsDBi54497
54498 [P28749-2]

PTM databases

iPTMnetiP28749
PhosphoSitePlusiP28749

Expressioni

Gene expression databases

BgeeiENSG00000080839
CleanExiHS_RBL1
ExpressionAtlasiP28749 baseline and differential
GenevisibleiP28749 HS

Organism-specific databases

HPAiHPA054962
HPA056525

Interactioni

Subunit structurei

Interacts with KMT5B, KMT5C and USP4 (By similarity). Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with AATF. Interacts with KDM5A.By similarity4 Publications
(Microbial infection) Interacts with SV40 and JC virus large T antigens.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111868, 75 interactors
CORUMiP28749
DIPiDIP-148N
ELMiP28749
IntActiP28749, 42 interactors
MINTiP28749
STRINGi9606.ENSP00000362768

Structurei

Secondary structure

11068
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi392 – 400Combined sources9
Turni401 – 403Combined sources3
Helixi410 – 417Combined sources8
Beta strandi419 – 421Combined sources3
Helixi424 – 442Combined sources19
Beta strandi447 – 449Combined sources3
Helixi454 – 477Combined sources24
Helixi480 – 483Combined sources4
Helixi489 – 492Combined sources4
Helixi495 – 512Combined sources18
Helixi521 – 525Combined sources5
Helixi530 – 533Combined sources4
Helixi535 – 543Combined sources9
Helixi549 – 564Combined sources16
Helixi566 – 568Combined sources3
Helixi573 – 580Combined sources8
Turni581 – 583Combined sources3
Helixi588 – 591Combined sources4
Helixi785 – 809Combined sources25
Helixi814 – 830Combined sources17
Helixi832 – 835Combined sources4
Helixi840 – 854Combined sources15
Beta strandi855 – 857Combined sources3
Helixi861 – 868Combined sources8
Helixi877 – 880Combined sources4
Beta strandi881 – 883Combined sources3
Helixi930 – 936Combined sources7
Helixi938 – 946Combined sources9
Beta strandi1001 – 1005Combined sources5
Turni1006 – 1008Combined sources3
Helixi1011 – 1023Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H28X-ray2.80E/F653-663[»]
4YOOX-ray2.40A391-600[»]
A781-972[»]
4YOSX-ray2.30A391-599[»]
4YOZX-ray2.25A391-593[»]
A777-972[»]
5TUVX-ray2.90C/F994-1031[»]
ProteinModelPortaliP28749
SMRiP28749
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP28749

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni385 – 949Pocket; binds T and E1AAdd BLAST565
Regioni385 – 584Domain AAdd BLAST200
Regioni585 – 780SpacerAdd BLAST196
Regioni781 – 949Domain BAdd BLAST169

Sequence similaritiesi

Belongs to the retinoblastoma protein (RB) family.Curated

Phylogenomic databases

eggNOGiKOG1010 Eukaryota
ENOG410XQF7 LUCA
GeneTreeiENSGT00530000063235
HOGENOMiHOG000273892
HOVERGENiHBG017710
InParanoidiP28749
KOiK04681
OMAiESLAWSH
OrthoDBiEOG091G0398
PhylomeDBiP28749
TreeFamiTF105568

Family and domain databases

CDDicd00043 CYCLIN, 1 hit
InterProiView protein in InterPro
IPR013763 Cyclin-like
IPR036915 Cyclin-like_sf
IPR002720 RB_A
IPR002719 RB_B
IPR015030 RB_C
IPR028309 RB_fam
IPR024599 RB_N
IPR028310 RBL1
PANTHERiPTHR13742 PTHR13742, 1 hit
PTHR13742:SF20 PTHR13742:SF20, 1 hit
PfamiView protein in Pfam
PF11934 DUF3452, 1 hit
PF01858 RB_A, 1 hit
PF01857 RB_B, 1 hit
PF08934 Rb_C, 1 hit
SMARTiView protein in SMART
SM00385 CYCLIN, 1 hit
SM01367 DUF3452, 1 hit
SM01368 RB_A, 1 hit
SM01369 Rb_C, 1 hit
SUPFAMiSSF47954 SSF47954, 3 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P28749-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MFEDKPHAEG AAVVAAAGEA LQALCQELNL DEGSAAEALD DFTAIRGNYS
60 70 80 90 100
LEGEVTHWLA CSLYVACRKS IIPTVGKGIM EGNCVSLTRI LRSAKLSLIQ
110 120 130 140 150
FFSKMKKWMD MSNLPQEFRE RIERLERNFE VSTVIFKKYE PIFLDIFQNP
160 170 180 190 200
YEEPPKLPRS RKQRRIPCSV KDLFNFCWTL FVYTKGNFRM IGDDLVNSYH
210 220 230 240 250
LLLCCLDLIF ANAIMCPNRQ DLLNPSFKGL PSDFHTADFT ASEEPPCIIA
260 270 280 290 300
VLCELHDGLL VEAKGIKEHY FKPYISKLFD RKILKGECLL DLSSFTDNSK
310 320 330 340 350
AVNKEYEEYV LTVGDFDERI FLGADAEEEI GTPRKFTRDT PLGKLTAQAN
360 370 380 390 400
VEYNLQQHFE KKRSFAPSTP LTGRRYLREK EAVITPVASA TQSVSRLQSI
410 420 430 440 450
VAGLKNAPSD QLINIFESCV RNPVENIMKI LKGIGETFCQ HYTQSTDEQP
460 470 480 490 500
GSHIDFAVNR LKLAEILYYK ILETVMVQET RRLHGMDMSV LLEQDIFHRS
510 520 530 540 550
LMACCLEIVL FAYSSPRTFP WIIEVLNLQP FYFYKVIEVV IRSEEGLSRD
560 570 580 590 600
MVKHLNSIEE QILESLAWSH DSALWEALQV SANKVPTCEE VIFPNNFETG
610 620 630 640 650
NGGNVQGHLP LMPMSPLMHP RVKEVRTDSG SLRRDMQPLS PISVHERYSS
660 670 680 690 700
PTAGSAKRRL FGEDPPKEML MDKIITEGTK LKIAPSSSIT AENVSILPGQ
710 720 730 740 750
TLLTMATAPV TGTTGHKVTI PLHGVANDAG EITLIPLSMN TNQESKVKSP
760 770 780 790 800
VSLTAHSLIG ASPKQTNLTK AQEVHSTGIN RPKRTGSLAL FYRKVYHLAS
810 820 830 840 850
VRLRDLCLKL DVSNELRRKI WTCFEFTLVH CPDLMKDRHL DQLLLCAFYI
860 870 880 890 900
MAKVTKEERT FQEIMKSYRN QPQANSHVYR SVLLKSIPRE VVAYNKNIND
910 920 930 940 950
DFEMIDCDLE DATKTPDCSS GPVKEERGDL IKFYNTIYVG RVKSFALKYD
960 970 980 990 1000
LANQDHMMDA PPLSPFPHIK QQPGSPRRIS QQHSIYISPH KNGSGLTPRS
1010 1020 1030 1040 1050
ALLYKFNGSP SKSLKDINNM IRQGEQRTKK RVIAIDSDAE SPAKRVCQEN
1060
DDVLLKRLQD VVSERANH
Length:1,068
Mass (Da):120,847
Last modified:March 7, 2006 - v3
Checksum:i2BC4876EA04BDB31
GO
Isoform 2 (identifier: P28749-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1013-1068: SLKDINNMIRQGEQRTKKRVIAIDSDAESPAKRVCQENDDVLLKRLQDVVSERANH → VR

Show »
Length:1,014
Mass (Da):114,688
Checksum:iCE1D47DBF365C4CB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti326Missing AA sequence (PubMed:11884610).Curated1
Sequence conflicti928G → S (PubMed:8319904).Curated1
Sequence conflicti928G → S (PubMed:1833063).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0344431035I → M. Corresponds to variant dbSNP:rs8114297Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0174961013 – 1068SLKDI…ERANH → VR in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14812 mRNA Translation: AAA02489.1
AK290380 mRNA Translation: BAF83069.1
AL136172 Genomic DNA No translation available.
AL365505 Genomic DNA No translation available.
AL391114 Genomic DNA No translation available.
CH471077 Genomic DNA Translation: EAW76088.1
BC032247 mRNA Translation: AAH32247.1
M74547 mRNA Translation: AAA36397.1
S78664 Genomic DNA Translation: AAD14290.1
CCDSiCCDS13289.1 [P28749-1]
CCDS13290.1 [P28749-2]
PIRiA47319 A40265
RefSeqiNP_002886.2, NM_002895.4 [P28749-1]
NP_899662.1, NM_183404.3 [P28749-2]
UniGeneiHs.207745

Genome annotation databases

EnsembliENST00000344359; ENSP00000343646; ENSG00000080839 [P28749-2]
ENST00000373664; ENSP00000362768; ENSG00000080839 [P28749-1]
GeneIDi5933
KEGGihsa:5933
UCSCiuc002xgi.5 human [P28749-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRBL1_HUMAN
AccessioniPrimary (citable) accession number: P28749
Secondary accession number(s): A8K2W5
, Q4VXA0, Q8N5K6, Q9H1L5, Q9H1M1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: March 7, 2006
Last modified: June 20, 2018
This is version 194 of the entry and version 3 of the sequence. See 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

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