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Q08999 (RBL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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-like protein 2
Alternative name(s):
130 kDa retinoblastoma-associated protein
Short name=p130
Retinoblastoma-related protein 2
Short name=RBR-2
pRb2
Gene names
Name:RBL2
Synonyms:RB2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1139 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 SUV420H1 and SUV420H2, 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, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor.

Subunit structure

Interacts with AATF. Interacts with SUV420H1, SUV420H2 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 RINT1. Interacts with PML (isoform PML-1 isoform PML-2 isoform PML-3 isoform PML-4and isoform PML-5) Ref.6 Ref.8 Ref.9 Ref.13

Subcellular location

Nucleus.

Developmental stage

G0-restricted expression.

Post-translational modification

During G0 and early G1 phase of the cell cycle, phosphorylated on Ser-639 and on 5 sites within the domain B. Phosphorylation on Ser-672 in G1 leads to its ubiquitin-dependent proteolysis. Ref.5 Ref.7

Sequence similarities

Belongs to the retinoblastoma protein (RB) family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P032552EBI-971439,EBI-2603114From a different organism.
DGKZQ13574-22EBI-971439,EBI-715527
LIN54Q6MZP710EBI-971439,EBI-1389411
Pax3P246103EBI-971439,EBI-1208116From a different organism.
PPP2CAP677752EBI-971439,EBI-712311
Sirt1Q923E42EBI-971439,EBI-1802585From a different organism.
Vsx2Q614124EBI-971439,EBI-1208174From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11391139Retinoblastoma-like protein 2
PRO_0000167841

Regions

Region417 – 1024608Pocket; binds E1A
Region417 – 616200Domain A
Region617 – 827211Spacer
Region828 – 1024197Domain B
Compositional bias9 – 168Poly-Pro
Compositional bias17 – 204Poly-Ala
Compositional bias23 – 264Poly-Glu
Compositional bias998 – 10014Poly-Glu

Amino acid modifications

Modified residue6391Phosphoserine Ref.5
Modified residue6421Phosphothreonine By similarity
Modified residue6621Phosphoserine Ref.12
Modified residue6721Phosphoserine Ref.7 Ref.12
Modified residue9481Phosphoserine By similarity
Modified residue9521Phosphoserine Ref.5
Modified residue9661Phosphoserine Ref.5
Modified residue9711Phosphoserine Probable
Modified residue9721Phosphoserine Probable
Modified residue9731Phosphoserine Probable
Modified residue9741Phosphothreonine Probable
Modified residue9811Phosphoserine Probable
Modified residue9821Phosphoserine Ref.5
Modified residue9861Phosphothreonine Ref.5
Modified residue10351Phosphoserine Ref.12

Natural variations

Natural variant991V → F. Ref.14
VAR_069377
Natural variant2101Y → C.
Corresponds to variant rs17800727 [ dbSNP | Ensembl ].
VAR_028437

Experimental info

Sequence conflict371P → S in CAA53661. Ref.1
Sequence conflict371P → S in AAC50479. Ref.4
Sequence conflict641A → P Ref.1
Sequence conflict641A → P Ref.4
Sequence conflict2061V → M in CAA52671. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q08999 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: D129032FB1F383D4

FASTA1,139128,367
        10         20         30         40         50         60 
MPSGGDQSPP PPPPPPAAAA SDEEEEDDGE AEDAAPPAES PTPQIQQRFD ELCSRLNMDE 

        70         80         90        100        110        120 
AARAEAWDSY RSMSESYTLE GNDLHWLACA LYVACRKSVP TVSKGTVEGN YVSLTRILKC 

       130        140        150        160        170        180 
SEQSLIEFFN KMKKWEDMAN LPPHFRERTE RLERNFTVSA VIFKKYEPIF QDIFKYPQEE 

       190        200        210        220        230        240 
QPRQQRGRKQ RRQPCTVSEI FHFCWVLFIY AKGNFPMISD DLVNSYHLLL CALDLVYGNA 

       250        260        270        280        290        300 
LQCSNRKELV NPNFKGLSED FHAKDSKPSS DPPCIIEKLC SLHDGLVLEA KGIKEHFWKP 

       310        320        330        340        350        360 
YIRKLYEKKL LKGKEENLTG FLEPGNFGES FKAINKAYEE YVLSVGNLDE RIFLGEDAEE 

       370        380        390        400        410        420 
EIGTLSRCLN AGSGTETAER VQMKNILQQH FDKSKALRIS TPLTGVRYIK ENSPCVTPVS 

       430        440        450        460        470        480 
TATHSLSRLH TMLTGLRNAP SEKLEQILRT CSRDPTQAIA NRLKEMFEIY SQHFQPDEDF 

       490        500        510        520        530        540 
SNCAKEIASK HFRFAEMLYY KVLESVIEQE QKRLGDMDLS GILEQDAFHR SLLACCLEVV 

       550        560        570        580        590        600 
TFSYKPPGNF PFITEIFDVP LYHFYKVIEV FIRAEDGLCR EVVKHLNQIE EQILDHLAWK 

       610        620        630        640        650        660 
PESPLWEKIR DNENRVPTCE EVMPPQNLER ADEICIAGSP LTPRRVTEVR ADTGGLGRSI 

       670        680        690        700        710        720 
TSPTTLYDRY SSPPASTTRR RLFVENDSPS DGGTPGRMPP QPLVNAVPVQ NVSGETVSVT 

       730        740        750        760        770        780 
PVPGQTLVTM ATATVTANNG QTVTIPVQGI ANENGGITFF PVQVNVGGQA QAVTGSIQPL 

       790        800        810        820        830        840 
SAQALAGSLS SQQVTGTTLQ VPGQVAIQQI SPGGQQQKQG QSVTSSSNRP RKTSSLSLFF 

       850        860        870        880        890        900 
RKVYHLAAVR LRDLCAKLDI SDELRKKIWT CFEFSIIQCP ELMMDRHLDQ LLMCAIYVMA 

       910        920        930        940        950        960 
KVTKEDKSFQ NIMRCYRTQP QARSQVYRSV LIKGKRKRRN SGSSDSRSHQ NSPTELNKDR 

       970        980        990       1000       1010       1020 
TSRDSSPVMR SSSTLPVPQP SSAPPTPTRL TGANSDMEEE ERGDLIQFYN NIYIKQIKTF 

      1030       1040       1050       1060       1070       1080 
AMKYSQANMD APPLSPYPFV RTGSPRRIQL SQNHPVYISP HKNETMLSPR EKIFYYFSNS 

      1090       1100       1110       1120       1130 
PSKRLREINS MIRTGETPTK KRGILLEDGS ESPAKRICPE NHSALLRRLQ DVANDRGSH 

« Hide

References

« Hide 'large scale' references
[1]"The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E."
Li Y., Graham C., Lacy S., Duncan A.M.V., Whyte P.
Genes Dev. 7:2366-2377(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta and Spleen.
[2]"Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins."
Hannon G.J., Demetrick D., Beach D.
Genes Dev. 7:2378-2391(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain."
Mayol X., Grana X., Baldi A., Sang N., Hu Q., Giordano A.
Oncogene 8:2561-2566(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 58-1139.
[4]"Genomic structure of the human retinoblastoma-related Rb2/p130 gene."
Baldi A., Boccia V., Claudio P.P., de Luca A., Giordano A.
Proc. Natl. Acad. Sci. U.S.A. 93:4629-4632(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-80.
Tissue: Placenta.
[5]"Phosphorylation of the retinoblastoma-related protein p130 in growth-arrested cells."
Canhoto A.J., Chestukhin A., Litovchick L., DeCaprio J.A.
Oncogene 19:5116-5122(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-639; SER-952; SER-966; SER-971; SER-972; SER-973; THR-974; SER-981; SER-982 AND THR-986, IDENTIFICATION BY MASS SPECTROMETRY.
[6]"Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb."
Bruno T., De Angelis R., De Nicola F., Barbato C., Di Padova M., Corbi N., Libri V., Benassi B., Mattei E., Chersi A., Soddu S., Floridi A., Passananti C., Fanciulli M.
Cancer Cell 2:387-399(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AATF.
[7]"The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2)."
Tedesco D., Lukas J., Reed S.I.
Genes Dev. 16:2946-2957(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-672.
[8]"The Rb-related p130 protein controls telomere lengthening through an interaction with a Rad50-interacting protein, RINT-1."
Kong L.-J., Meloni A.R., Nevins J.R.
Mol. Cell 22:63-71(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RINT1.
[9]"LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes."
Schmit F., Korenjak M., Mannefeld M., Schmitt K., Franke C., von Eyss B., Gagrica S., Haenel F., Brehm A., Gaubatz S.
Cell Cycle 6:1903-1913(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE DREAM COMPLEX.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662; SER-672 AND SER-1035, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence."
Martin N., Benhamed M., Nacerddine K., Demarque M.D., van Lohuizen M., Dejean A., Bischof O.
EMBO J. 31:95-109(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PML.
[14]"Diagnostic exome sequencing in persons with severe intellectual disability."
de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., Veltman J.A., Vissers L.E.
N. Engl. J. Med. 367:1921-1929(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHE-99.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X76061 mRNA. Translation: CAA53661.1.
S67171 mRNA. Translation: AAB29227.1.
X74594 mRNA. Translation: CAA52671.1.
U53220 Genomic DNA. Translation: AAC50479.1.
PIRA49370.
RefSeqNP_005602.3. NM_005611.3.
UniGeneHs.513609.

3D structure databases

ProteinModelPortalQ08999.
SMRQ08999. Positions 49-1041.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111869. 59 interactions.
DIPDIP-425N.
IntActQ08999. 33 interactions.
MINTMINT-102310.
STRING9606.ENSP00000262133.

PTM databases

PhosphoSiteQ08999.

Polymorphism databases

DMDM116242746.

Proteomic databases

PaxDbQ08999.
PRIDEQ08999.

Protocols and materials databases

DNASU5934.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262133; ENSP00000262133; ENSG00000103479.
GeneID5934.
KEGGhsa:5934.
UCSCuc002ehi.4. human.

Organism-specific databases

CTD5934.
GeneCardsGC16P053467.
HGNCHGNC:9894. RBL2.
HPACAB016547.
HPA019703.
MIM180203. gene.
neXtProtNX_Q08999.
PharmGKBPA34258.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG296920.
HOGENOMHOG000273892.
HOVERGENHBG017710.
InParanoidQ08999.
KOK16332.
OMAPPGNFPF.
OrthoDBEOG7P5T04.
PhylomeDBQ08999.
TreeFamTF105568.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.

Gene expression databases

ArrayExpressQ08999.
BgeeQ08999.
CleanExHS_RBL2.
GenevestigatorQ08999.

Family and domain databases

Gene3D1.10.472.10. 3 hits.
InterProIPR013763. Cyclin-like.
IPR028308. RB2.
IPR002720. RB_A.
IPR002719. RB_B.
IPR028309. RB_fam.
IPR024599. RB_N.
[Graphical view]
PANTHERPTHR13742. PTHR13742. 1 hit.
PTHR13742:SF8. PTHR13742:SF8. 1 hit.
PfamPF11934. DUF3452. 1 hit.
PF01858. RB_A. 1 hit.
PF01857. RB_B. 1 hit.
[Graphical view]
SMARTSM00385. CYCLIN. 2 hits.
[Graphical view]
SUPFAMSSF47954. SSF47954. 3 hits.
ProtoNetSearch...

Other

ChiTaRSRBL2. human.
GeneWikiRetinoblastoma-like_protein_2.
GenomeRNAi5934.
NextBio23132.
PROQ08999.
SOURCESearch...

Entry information

Entry nameRBL2_HUMAN
AccessionPrimary (citable) accession number: Q08999
Secondary accession number(s): Q15073, Q16084, Q92812
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 139 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM