Reviewed, UniProtKB/Swiss-Prot Q08999 (RBL2_HUMAN)

Names and origin

Protein names

Recommended name:
    Retinoblastoma-like protein 2
      Short name=RBR-2
Alternative name(s):
    PRB2
    130 kDa retinoblastoma-associated protein
    p130

Gene names

Name:	RBL2
Synonyms:	RB2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1139 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 and SUV420H2 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.
Subcellular location	Nucleus.
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 Ref.10
Miscellaneous	G0-restricted expression.
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
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of lipid kinase activity Inferred from direct assay. Source: UniProtKB regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.3 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DGKZ	Q13574-2	2	EBI-971439,EBI-715527
Pax3	P24610	2	EBI-971439,EBI-1208116	From a different organism.
Vsx2	Q61412	2	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	401	1	Phosphothreonine
	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
	Modified residue	662	1	Phosphoserine
	Modified residue	672	1	Phosphoserine Ref.7
	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
	Modified residue	986	1	Phosphothreonine Ref.5
	Modified residue	1019	1	Phosphothreonine Ref.10
	Modified residue	1035	1	Phosphoserine
Natural variations
	Natural variant	210	1	Y → C: dbSNP rs17800727.		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)
	Q08999-1 [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: 8253383] [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: 8253384] [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: 8361765] [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: 8643454] [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: 11042701] [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: 12450794] [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: 12435635] [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: 16600870] [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: 17671431] [Abstract] Cited for: IDENTIFICATION IN THE DREAM COMPLEX.
[10]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1019, MASS SPECTROMETRY.
[11]	"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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401; SER-639; THR-642; SER-982 AND THR-986, MASS SPECTROMETRY.
[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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401; SER-662; SER-672; SER-982 AND SER-1035, MASS SPECTROMETRY. Tissue: T-cell.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.513609
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:425N.
IntAct	Q08999. 20 interactions.
STRING	Q08999.
PTM databases
PhosphoSite	Q08999.
Proteomic databases
PRIDE	Q08999.
Genome annotation databases
Ensembl	ENST00000262133; ENSP00000262133; ENSG00000103479; Homo sapiens. [Genome view]
GeneID	5934.
KEGG	hsa:5934.
UCSC	uc002ehi.2. human.
Organism-specific databases
CTD	5934.
GeneCards	GC16P052025.
H-InvDB	HIX0026969.
HGNC	HGNC:9894. RBL2.
HPA	CAB016547. HPA019703.
MIM	180203. gene.
PharmGKB	PA34258.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q08999.
HOVERGEN	Q08999.
OMA	LLMCAIY
OrthoDB	EOG9WDGXZ
Enzyme and pathway databases
Pathway_Interaction_DB	foxopathway. FoxO family signaling.
Gene expression databases
ArrayExpress	Q08999.
Bgee	Q08999.
CleanEx	HS_RBL2.
Genevestigator	Q08999.
GermOnline	ENSG00000103479. Homo sapiens.
Family and domain databases
InterPro	IPR006670. Cyclin. IPR011028. Cyclin-like. IPR013763. Cyclin_related. IPR002720. RB_A. IPR002719. RB_B. [Graphical view]
Gene3D	G3DSA:1.10.472.10. Cyclin_related. 2 hits.
Pfam	PF01858. RB_A. 1 hit. PF01857. RB_B. 1 hit. [Graphical view]
SMART	SM00385. CYCLIN. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
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:	November 24, 2009
This is version 95 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.