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Protein

Retinoblastoma-like protein 1

Gene

RBL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Repressor

Keywords - Biological processi

Cell cycle, Host-virus interaction, Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000080839-MONOMER.
ReactomeiR-HSA-1538133. G0 and Early G1.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
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

HGNCiHGNC:9893. RBL1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.

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. Interacts with SV40 and JC virus large T antigens.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
P032553EBI-971402,EBI-2603114From a different organism.
BEGAINQ9BUH82EBI-971402,EBI-742722
CDK4P118022EBI-971402,EBI-295644
DGKZQ13574-22EBI-971402,EBI-715527
DHX30Q7L2E34EBI-971402,EBI-1211456
DYRK1AQ136273EBI-971402,EBI-1053596
DYRK1BQ9Y4633EBI-971402,EBI-634187
E7P031292EBI-971402,EBI-866453From a different organism.
FOXO3O435243EBI-971402,EBI-1644164
IRF3Q146532EBI-971402,EBI-2650369
NR2E3Q9Y5X42EBI-971402,EBI-7216962
Pax3P246103EBI-971402,EBI-1208116From a different organism.
PPP2CAP677752EBI-971402,EBI-712311
Sirt1Q923E42EBI-971402,EBI-1802585From a different organism.

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111868. 71 interactors.
DIPiDIP-148N.
IntActiP28749. 43 interactors.
MINTiMINT-1353484.
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
Helixi861 – 868Combined sources8
Helixi877 – 880Combined sources4
Beta strandi881 – 883Combined sources3
Helixi894 – 900Combined sources7
Helixi902 – 910Combined sources9

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[»]
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.
OMAiSCMRNPM.
OrthoDBiEOG091G0398.
PhylomeDBiP28749.
TreeFamiTF105568.

Family and domain databases

Gene3Di1.10.472.10. 3 hits.
InterProiIPR013763. Cyclin-like.
IPR002720. RB_A.
IPR002719. RB_B.
IPR015030. RB_C.
IPR028309. RB_fam.
IPR024599. RB_N.
IPR028310. RBL1.
[Graphical view]
PANTHERiPTHR13742. PTHR13742. 4 hits.
PTHR13742:SF20. PTHR13742:SF20. 4 hits.
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. 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 rs8114297dbSNPEnsembl.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, AL365505, AL391114 Genomic DNA. Translation: CAI95716.1.
AL365505, AL136172, AL391114 Genomic DNA. Translation: CAI95177.1.
AL391114, AL136172, AL365505 Genomic DNA. Translation: CAI95151.1.
AL365505, AL136172, AL391114 Genomic DNA. Translation: CAI95178.1.
AL391114, AL136172, AL365505 Genomic DNA. Translation: CAI95152.1.
AL136172, AL365505, AL391114 Genomic DNA. Translation: CAI95717.1.
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14812 mRNA. Translation: AAA02489.1.
AK290380 mRNA. Translation: BAF83069.1.
AL136172, AL365505, AL391114 Genomic DNA. Translation: CAI95716.1.
AL365505, AL136172, AL391114 Genomic DNA. Translation: CAI95177.1.
AL391114, AL136172, AL365505 Genomic DNA. Translation: CAI95151.1.
AL365505, AL136172, AL391114 Genomic DNA. Translation: CAI95178.1.
AL391114, AL136172, AL365505 Genomic DNA. Translation: CAI95152.1.
AL136172, AL365505, AL391114 Genomic DNA. Translation: CAI95717.1.
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.

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[»]
ProteinModelPortaliP28749.
SMRiP28749.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111868. 71 interactors.
DIPiDIP-148N.
IntActiP28749. 43 interactors.
MINTiMINT-1353484.
STRINGi9606.ENSP00000362768.

PTM databases

iPTMnetiP28749.
PhosphoSitePlusiP28749.

Polymorphism and mutation databases

DMDMi90103515.

Proteomic databases

EPDiP28749.
MaxQBiP28749.
PaxDbiP28749.
PeptideAtlasiP28749.
PRIDEiP28749.

Protocols and materials databases

DNASUi5933.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5933.
DisGeNETi5933.
GeneCardsiRBL1.
H-InvDBHIX0040570.
HGNCiHGNC:9893. RBL1.
HPAiHPA054962.
HPA056525.
MIMi116957. gene.
neXtProtiNX_P28749.
OpenTargetsiENSG00000080839.
PharmGKBiPA34257.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000080839-MONOMER.
ReactomeiR-HSA-1538133. G0 and Early G1.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
R-HSA-69231. Cyclin D associated events in G1.
SIGNORiP28749.

Miscellaneous databases

ChiTaRSiRBL1. human.
EvolutionaryTraceiP28749.
GeneWikiiRetinoblastoma-like_protein_1.
GenomeRNAii5933.
PROiP28749.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080839.
CleanExiHS_RBL1.
ExpressionAtlasiP28749. baseline and differential.
GenevisibleiP28749. HS.

Family and domain databases

Gene3Di1.10.472.10. 3 hits.
InterProiIPR013763. Cyclin-like.
IPR002720. RB_A.
IPR002719. RB_B.
IPR015030. RB_C.
IPR028309. RB_fam.
IPR024599. RB_N.
IPR028310. RBL1.
[Graphical view]
PANTHERiPTHR13742. PTHR13742. 4 hits.
PTHR13742:SF20. PTHR13742:SF20. 4 hits.
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. 3 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiRBL1_HUMAN
AccessioniPrimary (citable) accession number: P28749
Secondary accession number(s): A8K2W5
, Q4VXA0, Q8N5K6, Q9H1L5, Q9H1M1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: March 7, 2006
Last modified: November 30, 2016
This is version 176 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.