Reviewed, UniProtKB/Swiss-Prot P06400 (RB_HUMAN)

Names and origin

Protein names

Recommended name:
    Retinoblastoma-associated protein
Alternative name(s):
    pRb
      Short name=Rb
    pp110
    p105-Rb

Gene names

Name:

RB1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	928 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 that acts as a tumor suppressor. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. 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 SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.
Subunit structure	Interacts with ATAD5 By similarity. The hypophosphorylated form interacts with and sequesters the E2F1 transcription factor. The unphosphorylated form interacts with ARID3B, JARID1A, SUV39H1, MJD2A/JHDM3A and THOC1. Interacts with the N-terminal domain of TAF1. Interacts with AATF, DNMT1, LIN9, LMNA, SUV420H1, SUV420H2, PELP1 and TMPO-alpha. May interact with NDC80. Interacts with EID1 and UBR4. Interacts with ARID4A and JARID1B. Interacts with E4F1. Interacts with adenovirus E1A protein, HPV E7 protein and SV40 large T antigen.
Subcellular location	Nucleus.
Tissue specificity	Expressed in the retina.
Post-translational modification	Phosphorylated in G1, thereby releasing E2F1 which is then able to activate cell growth. Dephosphorylated at the late M phase. SV40 large T antigen, HPV E7 and adenovirus E1A bind to the underphosphorylated, active form of pRb.
Involvement in disease	Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:180200]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ("cat eye") is investigated. Defects in RB1 are a cause of bladder cancer [MIM:109800]. Defects in RB1 are a cause of osteogenic sarcoma [MIM:259500].
Sequence similarities	Belongs to the retinoblastoma protein (RB) family.

Ontologies

Keywords
Biological process	Cell cycle Host-virus interaction Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	DNA-binding
Molecular function	Anti-oncogene Chromatin regulator Repressor
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	G1 phase Traceable author statement. Source: UniProtKB M phase Non-traceable author statement. Source: UniProtKB androgen receptor signaling pathway Non-traceable author statement. Source: UniProtKB cell cycle checkpoint Traceable author statement. Source: ProtInc negative regulation of cell growth Traceable author statement. Source: UniProtKB negative regulation of protein kinase activity Ref.22 Inferred from physical interaction. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc positive regulation of transcription, DNA-dependent Non-traceable author statement. Source: UniProtKB regulation of lipid kinase activity Inferred from direct assay. Source: UniProtKB
Cellular component	PML body Inferred from direct assay. Source: UniProtKB chromatin Ref.1 Traceable author statement. Source: ProtInc
Molecular function	androgen receptor binding Non-traceable author statement. Source: UniProtKB kinase binding Inferred from direct assay. Source: UniProtKB transcription coactivator activity Non-traceable author statement. Source: UniProtKB transcription factor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2	P24941	1	EBI-491274,EBI-375096
Cdk4	P30285	2	EBI-491274,EBI-847225	From a different organism.
DGKZ	Q13574-2	5	EBI-491274,EBI-715527
E2F1	Q01094	1	EBI-491274,EBI-448924
E7	P06465	1	EBI-491274,EBI-963841	From a different organism.
HDAC1	Q13547	1	EBI-491274,EBI-301834
Hmga2	P52927	4	EBI-491274,EBI-912574	From a different organism.
MORF4L2	Q15014	1	EBI-491274,EBI-399257
NCOA6	Q14686	2	EBI-491274,EBI-78670
PA2G4	Q9UQ80	2	EBI-491274,EBI-924893
PPP1CA	P62136	2	EBI-491274,EBI-357253
Ppp1cb	P62142	1	EBI-491274,EBI-352326	From a different organism.
PRMT2	P55345	3	EBI-491274,EBI-78458
PSMD10	O75832	1	EBI-491274,EBI-752185
Smarca4	Q3TUD7	1	EBI-491274,EBI-1210244	From a different organism.
TAF1	P21675	1	EBI-491274,EBI-491289

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 928

928

Retinoblastoma-associated protein

PRO_0000167836

Regions

Region

373 – 771

399

Pocket; binds T and E1A

Region

373 – 579

207

Domain A

Region

580 – 639

60

Spacer

Region

640 – 771

132

Domain B

Region

771 – 928

158

Domain C; mediates interaction with E4F1

Compositional bias

10 – 18

9

Poly-Ala

Compositional bias

20 – 29

10

Poly-Pro

Amino acid modifications

Modified residue

249

1

Phosphoserine; by CDC2

Modified residue

252

1

Phosphothreonine; by CDC2

Modified residue

356

1

Phosphothreonine

Modified residue

373

1

Phosphothreonine; by CDC2

Modified residue

807

1

Phosphoserine; by CDC2

Modified residue

811

1

Phosphoserine; by CDC2

Modified residue

826

1

Phosphothreonine By similarity

Natural variations

Natural variant

72

1

E → Q in RB.

VAR_005572

Natural variant

137

1

E → D in RB; unilateral form.

VAR_005573

Natural variant

185

1

I → T in RB.

VAR_005574

Natural variant

310

1

G → E in RB; could be a polymorphism.

VAR_010045

Natural variant

358

1

R → G in RB.

VAR_010046

Natural variant

358

1

R → Q in RB.

VAR_005575

Natural variant

436

1

Q → K

VAR_019379

Natural variant

447

1

K → Q in RB.

VAR_010048

Natural variant

457

1

M → R in RB.

VAR_005576

Natural variant

480

1

Missing in RB; mild form.

VAR_005577

Natural variant

500

1

R → G in RB.

VAR_011580

Natural variant

525

1

A → G: dbSNP rs4151539.

VAR_019380

Natural variant

530

1

K → R in RB.

VAR_010049

Natural variant

549

1

H → Y in RB.

VAR_005578

Natural variant

567

1

S → L in RB.

VAR_005579

Natural variant

616

1

K → E in RB.

VAR_011581

Natural variant

635

1

A → P in RB.

VAR_005580

Natural variant

654

1

V → E in RB.

VAR_005581

Natural variant

657

1

L → P in RB.

VAR_010050

Natural variant

661

1

R → W in RB; mild form.

VAR_005582

Natural variant

662

1

L → P in RB.

VAR_005583

Natural variant

673

1

H → P in RB.

VAR_005584

Natural variant

685

1

Q → P in RB.

VAR_005585

Natural variant

706

1

C → Y in RB.

VAR_005586

Natural variant

712

1

C → R in RB.

VAR_005587

Natural variant

746

1

E → G: dbSNP rs3092905.

VAR_034442

Natural variant

803

1

N → K in RB.

VAR_005588

Experimental info

Sequence conflict

500 – 501

2

RS → SN in AAN64133. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

928

Helix Strand Turn

Details...

Helix

55 – 63

9

Helix

68 – 82

15

Helix

95 – 110

16

Helix

117 – 124

8

Helix

128 – 135

8

Helix

142 – 172

31

Beta strand

180 – 182

3

Helix

188 – 204

17

Helix

212 – 228

17

Helix

232 – 234

3

Turn

237 – 240

4

Helix

241 – 243

3

Helix

272 – 281

10

Helix

285 – 294

10

Helix

296 – 299

4

Helix

314 – 328

15

Helix

333 – 338

6

Helix

341 – 343

3

Helix

347 – 353

7

Helix

384 – 390

7

Helix

398 – 405

8

Beta strand

407 – 409

3

Helix

412 – 434

23

Helix

439 – 468

30

Helix

474 – 477

4

Helix

480 – 497

18

Turn

498 – 500

3

Beta strand

504 – 506

3

Helix

516 – 521

6

Helix

525 – 538

14

Helix

544 – 559

16

Helix

568 – 576

9