Reviewed,
UniProtKB/Swiss-Prot P28749 (RBL1_HUMAN)
Last modified
December 15, 2009.
Version 105.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Retinoblastoma-like protein 1 Alternative name(s): PRB1 107 kDa retinoblastoma-associated protein p107 | ||
| Gene names |
| ||
| 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 | 1068 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. 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. |
| Subunit structure | 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 AATF. Interacts with KDM5A. Interacts with SV40 and JC virus large T antigens. |
| Subcellular location | Nucleus Potential. |
| Post-translational modification | 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. Ref.8 Ref.12 |
| 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 | Alternative splicing Polymorphism |
| Disease | Tumor suppressor |
| Molecular function | Chromatin regulator Repressor |
| PTM | Phosphoprotein |
| Technical term | 3D-structure Complete proteome Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | cell cycle Inferred from electronic annotation. Source: UniProtKB-KW chromatin modificationInferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organismsInferred from electronic annotation. Source: UniProtKB-KW regulation of lipid kinase activityInferred from direct assay. Source: UniProtKB transcriptionInferred from electronic annotation. Source: UniProtKB-KW |
| Molecular function | transcription factor binding Ref.13 Inferred from physical interaction. Source: UniProtKB |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| BEGAIN | Q9BUH8 | 1 | EBI-971402,EBI-742722 | |
| Cenpf | Q155P7 | 1 | EBI-971402,EBI-2211248 | From a different organism. |
| DGKZ | Q13574-2 | 2 | EBI-971402,EBI-715527 | |
| Pax3 | P24610 | 2 | EBI-971402,EBI-1208116 | From a different organism. |
| Vsx2 | Q61412 | 1 | EBI-971402,EBI-1208174 | From a different organism. |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P28749-1) 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. | ||||||
| Isoform 2 (identifier: P28749-2) The sequence of this isoform differs from the canonical sequence as follows: 1013-1068: SLKDINNMIRQGEQRTKKRVIAIDSDAESPAKRVCQENDDVLLKRLQDVVSERANH → VR |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1068 | 1068 | Retinoblastoma-like protein 1 | PRO_0000167839 | |||||
Regions | |||||||||
| Region | 385 – 949 | 565 | Pocket; binds T and E1A | ||||||
| Region | 385 – 584 | 200 | Domain A | ||||||
| Region | 585 – 780 | 196 | Spacer | ||||||
| Region | 781 – 949 | 169 | Domain B | ||||||
Amino acid modifications | |||||||||
| Modified residue | 332 | 1 | Phosphothreonine; by CDK2 Ref.8 | ||||||
| Modified residue | 369 | 1 | Phosphothreonine; by CDK4 Ref.8 Ref.12 | ||||||
| Modified residue | 385 | 1 | Phosphothreonine; by CDK2 Ref.8 | ||||||
| Modified residue | 640 | 1 | Phosphoserine; by CDK2 and CDK4 Ref.8 | ||||||
| Modified residue | 650 | 1 | Phosphoserine Ref.12 | ||||||
| Modified residue | 749 | 1 | Phosphoserine | ||||||
| Modified residue | 762 | 1 | Phosphoserine; by CDK2 Ref.8 | ||||||
| Modified residue | 964 | 1 | Phosphoserine; by CDK2 and CDK4 Ref.8 | ||||||
| Modified residue | 975 | 1 | Phosphoserine; by CDK2 and CDK4 Ref.8 | ||||||
| Modified residue | 988 | 1 | Phosphoserine; by CDK2 Ref.8 | ||||||
| Modified residue | 997 | 1 | Phosphothreonine; by CDK2 Ref.8 | ||||||
| Modified residue | 1009 | 1 | Phosphoserine; by CDK2 Ref.8 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1013 – 1068 | 56 | SLKDI…ERANH → VR in isoform 2. | VSP_017496 | |||||
| Natural variant | 1035 | 1 | I → M: dbSNP rs8114297. | VAR_034443 | |||||
Experimental info | |||||||||
| Mutagenesis | 640 | 1 | S → A: Strongly reduces phosphorylation by CDK2 and CDK4. Ref.8 | ||||||
| Mutagenesis | 643 | 1 | S → R: No effect on S-640 phosphorylation, but strongly increases S-640 phosphorylation; when associated to 657-A--A-660. Ref.8 | ||||||
| Mutagenesis | 650 | 1 | S → A: No effect on phosphorylation by CDK2. Ref.8 | ||||||
| Mutagenesis | 657 – 660 | 4 | KRRL → AAAA: Reduces S-640 phosphorylation by CDK2 and CDK4. Ref.8 | ||||||
| Sequence conflict | 326 | 1 | Missing AA sequence Ref.8 | ||||||
| Sequence conflict | 928 | 1 | G → S Ref.1 | ||||||
| Sequence conflict | 928 | 1 | G → S Ref.6 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein." Zhu L., van den Heuvel S., Helin K., Fattaey A., Ewen M., Livingston D., Dyson N., Harlow E. Genes Dev. 7:1111-1125(1993) [PubMed: 8319904] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Tongue. |
| [3] | "The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. Rogers J.Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis. |
| [6] | "Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein." Ewen M.E., Xing Y., Lawrence J.B., Livingston D.M. Cell 66:1155-1164(1991) [PubMed: 1833063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 134-1068 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. |
| [7] | "Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins." Zhu L., Zhu L., Xie E., Chang L.S. Mol. Cell. Biol. 15:3552-3562(1995) [PubMed: 7791762] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52. |
| [8] | "Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4." Leng X., Noble M., Adams P.D., Qin J., Harper J.W. Mol. Cell. Biol. 22:2242-2254(2002) [PubMed: 11884610] [Abstract] Cited for: PROTEIN SEQUENCE OF 320-334; 364-374; 635-657; 949-977 AND 1006-1012, PHOSPHORYLATION AT THR-332; THR-369; THR-385; SER-640; SER-762; SER-964; SER-975; SER-988; THR-997 AND SER-1009, MUTAGENESIS OF SER-640; SER-643; SER-650 AND 657-LYS--LEU-660, MASS SPECTROMETRY. |
| [9] | "The cellular 107K protein that binds to adenovirus E1A also associates with the large T antigens of SV40 and JC virus." Dyson N., Buchkovich K., Whyte P., Harlow E. Cell 58:249-255(1989) [PubMed: 2546678] [Abstract] Cited for: INTERACTION WITH SV40 AND JC VIRUS LARGE T ANTIGEN. |
| [10] | "Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein." Kim Y.W., Otterson G.A., Kratzke R.A., Coxon A.B., Kaye F.J. Mol. Cell. Biol. 14:7256-7264(1994) [PubMed: 7935440] [Abstract] Cited for: INTERACTION WITH KDM5A. |
| [11] | "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. |
| [12] | "Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4." Farkas T., Hansen K., Holm K., Lukas J., Bartek J. J. Biol. Chem. 277:26741-26752(2002) [PubMed: 12006580] [Abstract] Cited for: PHOSPHORYLATION AT THR-369 AND SER-650. |
| [13] | "Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release." Rubin S.M., Gall A.-L., Zheng N., Pavletich N.P. Cell 123:1093-1106(2005) [PubMed: 16360038] [Abstract] Cited for: INTERACTION WITH WITH E2F4 AND TFDP1. |
| [14] | "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. |
| [15] | "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-332; THR-385; SER-749 AND SER-762, MASS SPECTROMETRY. Tissue: T-cell. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | |||||||||||||
| IPI | IPI00005139. IPI00375494. | ||||||||||||
| PIR | A40265. A47319. | ||||||||||||
| RefSeq | NP_002886.2. NP_899662.1. | ||||||||||||
| UniGene | Hs.207745 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP-148N. | ||||||||||||
| IntAct | P28749. 20 interactions. | ||||||||||||
| STRING | P28749. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P28749. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | P28749. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000373664; ENSP00000362768; ENSG00000080839; Homo sapiens. [Genome view] | ||||||||||||
| GeneID | 5933. | ||||||||||||
| KEGG | hsa:5933. | ||||||||||||
| UCSC | uc002xgi.1. human. uc002xgj.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 5933. | ||||||||||||
| GeneCards | GC20M035059. | ||||||||||||
| HGNC | HGNC:9893. RBL1. | ||||||||||||
| MIM | 116957. gene. | ||||||||||||
| PharmGKB | PA34257. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | HBG358205. | ||||||||||||
| HOVERGEN | P28749. | ||||||||||||
| InParanoid | P28749. | ||||||||||||
| OMA | KQRRIPC. | ||||||||||||
| OrthoDB | EOG9WDGXZ. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| Pathway_Interaction_DB | smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P28749. | ||||||||||||
| Bgee | P28749. | ||||||||||||
| CleanEx | HS_RBL1. | ||||||||||||
| Genevestigator | P28749. | ||||||||||||
| GermOnline | ENSG00000080839. 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. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 23126. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | RBL1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P28749 Secondary accession number(s): A8K2W5 Q9H1M1 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 20 Human chromosome 20: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


