Q08999 (RBL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1139 AA.
Sequence status	Complete.
Protein existence	Evidence 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-4 and isoform PML-5). Ref.6 Ref.8 Ref.9 Ref.12
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.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
Ligand	DNA-binding
Molecular function	Chromatin regulator Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1 phase of mitotic cell cycle Traceable author statement. Source: Reactome chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of cell cycle Inferred from electronic annotation. Source: InterPro regulation of lipid kinase activity Inferred from direct assay PubMed 16286473. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleolus Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DGKZ	Q13574-2	2	EBI-971439,EBI-715527
Pax3	P24610	3	EBI-971439,EBI-1208116	From a different organism.
Sirt1	Q923E4	2	EBI-971439,EBI-1802585	From a different organism.
Vsx2	Q61412	4	EBI-971439,EBI-1208174	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1139	1139	Retinoblastoma-like protein 2		PRO_0000167841
Regions
	Region	417 – 1024	608	Pocket; binds E1A
	Region	417 – 616	200	Domain A
	Region	617 – 827	211	Spacer
	Region	828 – 1024	197	Domain B
	Compositional bias	9 – 16	8	Poly-Pro
	Compositional bias	17 – 20	4	Poly-Ala
	Compositional bias	23 – 26	4	Poly-Glu
	Compositional bias	998 – 1001	4	Poly-Glu
Amino acid modifications
	Modified residue	413	1	Phosphoserine By similarity
	Modified residue	417	1	Phosphothreonine By similarity
	Modified residue	639	1	Phosphoserine Ref.5
	Modified residue	642	1	Phosphothreonine By similarity
	Modified residue	662	1	Phosphoserine Ref.11
	Modified residue	672	1	Phosphoserine Ref.7 Ref.11
	Modified residue	948	1	Phosphoserine By similarity
	Modified residue	952	1	Phosphoserine Ref.5
	Modified residue	966	1	Phosphoserine Ref.5
	Modified residue	971	1	Phosphoserine Probable
	Modified residue	972	1	Phosphoserine Probable
	Modified residue	973	1	Phosphoserine Probable
	Modified residue	974	1	Phosphothreonine Probable
	Modified residue	981	1	Phosphoserine Probable
	Modified residue	982	1	Phosphoserine Ref.5
	Modified residue	986	1	Phosphothreonine Ref.5
	Modified residue	1035	1	Phosphoserine Ref.11
Natural variations
	Natural variant	210	1	Y → C. Corresponds to variant rs17800727 [ dbSNP | Ensembl ].		VAR_028437
Experimental info
	Sequence conflict	37	1	P → S in CAA53661. Ref.1
	Sequence conflict	37	1	P → S in AAC50479. Ref.4
	Sequence conflict	64	1	A → P Ref.1
	Sequence conflict	64	1	A → P Ref.4
	Sequence conflict	206	1	V → M in CAA52671. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q08999 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: D129032FB1F383D4	FASTA	1,139	128,367
	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

References

	« Hide 'large scale' referencesShow '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, 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]	"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].
[11]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
IPI	IPI00304028.
PIR	A49370.
RefSeq	NP_005602.3. NM_005611.3.
UniGene	Hs.513609.
3D structure databases
ProteinModelPortal	Q08999.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-425N.
IntAct	Q08999. 25 interactions.
MINT	MINT-102310.
STRING	9606.ENSP00000262133.
PTM databases
PhosphoSite	Q08999.
Polymorphism databases
DMDM	116242746.
Proteomic databases
PaxDb	Q08999.
PRIDE	Q08999.
Protocols and materials databases
DNASU	5934.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262133; ENSP00000262133; ENSG00000103479.
GeneID	5934.
KEGG	hsa:5934.
UCSC	uc002ehi.4. human.
Organism-specific databases
CTD	5934.
GeneCards	GC16P053467.
HGNC	HGNC:9894. RBL2.
HPA	CAB016547. HPA019703.
MIM	180203. gene.
neXtProt	NX_Q08999.
PharmGKB	PA34258.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG296920.
HOGENOM	HOG000273892.
HOVERGEN	HBG017710.
InParanoid	Q08999.
KO	K16332.
OMA	PPGNFPF.
OrthoDB	EOG4PNXG9.
PhylomeDB	Q08999.
Enzyme and pathway databases
Pathway_Interaction_DB	foxopathway. FoxO family signaling.
Reactome	REACT_115566. Cell Cycle.
Gene expression databases
ArrayExpress	Q08999.
Bgee	Q08999.
CleanEx	HS_RBL2.
Genevestigator	Q08999.
GermOnline	ENSG00000103479. Homo sapiens.
Family and domain databases
Gene3D	1.10.472.10. 3 hits.
InterPro	IPR013763. Cyclin-like. IPR024599. DUF3452_retinoblatoma-assoc. IPR002720. RB_A. IPR002719. RB_B. [Graphical view]
Pfam	PF11934. DUF3452. 1 hit. PF01858. RB_A. 1 hit. PF01857. RB_B. 1 hit. [Graphical view]
SMART	SM00385. CYCLIN. 2 hits. [Graphical view]
SUPFAM	SSF47954. Cyclin_like. 2 hits.
ProtoNet	Search...
Other
ChiTaRS	RBL2. human.
GenomeRNAi	5934.
NextBio	23132.
SOURCE	Search...

Entry information

Entry name

RBL2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 129 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.