Retinoblastoma-like protein 2

RBL2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4XI9, 5C1D
Identifiers
Aliases	RBL2 , P130, Rb2, retinoblastoma-like 2, RB transcriptional corepressor like 2, BRUWAG
External IDs	OMIM: 180203; MGI: 105085; HomoloGene: 4098; GeneCards: RBL2; OMA:RBL2 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) [1] Band 16q12.2 Start 53,433,977 bp [1] End 53,491,648 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8 C4|8 44.25 cM Start 91,796,685 bp [2] End 91,850,472 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in germinal epithelium superficial temporal artery epithelium of nasopharynx Achilles tendon lymph node cardia tonsil body of pancreas pylorus mucosa of paranasal sinus Top expressed in parotid gland muscle of thigh spermatid saccule medial head of gastrocnemius muscle submandibular gland stroma of bone marrow temporal muscle triceps brachii muscle thymus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein binding promoter-specific chromatin binding DNA-binding transcription repressor activity, RNA polymerase II-specific Cellular component nucleolus extracellular exosome nucleus transcription regulator complex nucleoplasm cytosol chromatin Biological process regulation of transcription by RNA polymerase II regulation of cell cycle cell cycle regulation of transcription, DNA-templated transcription, DNA-templated regulation of lipid kinase activity DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest negative regulation of gene expression negative regulation of transcription by RNA polymerase II chromatin organization regulation of mitotic cell cycle cell differentiation regulation of cell division negative regulation of G1/S transition of mitotic cell cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5934 19651 Ensembl ENSG00000103479 ENSMUSG00000031666 UniProt Q08999 Q64700 RefSeq (mRNA) NM_005611 NM_001323608 NM_001323609 NM_001323610 NM_001323611 NM_001282000 NM_001282001 NM_011250 RefSeq (protein) NP_001310537 NP_001310538 NP_001310539 NP_001310540 NP_005602 NP_001268929 NP_001268930 NP_035380 Location (UCSC) Chr 16: 53.43 – 53.49 Mb Chr 8: 91.8 – 91.85 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Retinoblastoma-like protein 2 is a protein that in humans is encoded by the RBL2 gene. ^{[5] [6]} RBL2 is one of three retinoblastoma proteins encoded in the human genome (along with Rb and RBL1).

Interactions

Retinoblastoma-like protein 2 has been shown to interact with:

• BRCA1, ^[7]
• BRF1 ^[8]
• C-Raf, ^[9]
• Cyclin E1, ^{[10] [11]}
• Cyclin-dependent kinase 2, ^{[10] [12]}
• HDAC1, ^{[13] [14]}
• Prohibitin, ^[15] and
• RBBP8. ^{[16] [17]}

Human disease

Mutations in RBL2 have been linked to a severe neurodevelopmental disorder characterised by morphological and behavioural abnormalities. Symptoms include intellectual disability, developmental delay, microcephaly, dysmorphic features, gait abnormalities, and siezures. ^{[18] [19] [20]}

The genetic basis of RBL2-linked disease is caused by bi-allelic loss-of-function mutations (including nonsense mutations, frameshifts,splicing mutations, and deletions. ^[18]

RBL2-linked disease is a rare genetic disorder with only 35 patients identified worldwide (2025). ^[18]

See also

• Pocket protein family

References

1. GRCh38: Ensembl release 89: ENSG00000103479 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031666 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Mayol X, Graña X, Baldi A, Sang N, Hu Q, Giordano A (Sep 1993). "Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain". Oncogene. 8 (9): 2561–6. PMID   8361765.
6. Baldi A, Boccia V, Claudio PP, De Luca A, Giordano A (May 1996). "Genomic structure of the human retinoblastoma-related Rb2/p130 gene". Proceedings of the National Academy of Sciences of the United States of America. 93 (10): 4629–32. Bibcode:1996PNAS...93.4629B. doi: 10.1073/pnas.93.10.4629 . PMC   39329 . PMID   8643454.
7. Fan S, Yuan R, Ma YX, Xiong J, Meng Q, Erdos M, Zhao JN, Goldberg ID, Pestell RG, Rosen EM (Aug 2001). "Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding". Oncogene. 20 (35): 4827–41. doi: 10.1038/sj.onc.1204666 . PMID   11521194.
8. Sutcliffe JE, Cairns CA, McLees A, Allison SJ, Tosh K, White RJ (Jun 1999). "RNA polymerase III transcription factor IIIB is a target for repression by pocket proteins p107 and p130". Molecular and Cellular Biology. 19 (6): 4255–61. doi:10.1128/mcb.19.6.4255. PMC   104385 . PMID   10330166.
9. Wang S, Ghosh RN, Chellappan SP (Dec 1998). "Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation". Molecular and Cellular Biology. 18 (12): 7487–98. doi:10.1128/mcb.18.12.7487. PMC   109329 . PMID   9819434.
10. Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (Feb 1999). "Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest". Molecular and Cellular Biology. 19 (2): 1460–9. doi:10.1128/mcb.19.2.1460. PMC   116074 . PMID   9891079.
11. Li Y, Graham C, Lacy S, Duncan AM, Whyte P (Dec 1993). "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". Genes & Development. 7 (12A): 2366–77. doi: 10.1101/gad.7.12a.2366 . PMID   8253383.
12. Lacy S, Whyte P (May 1997). "Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes". Oncogene. 14 (20): 2395–406. doi:10.1038/sj.onc.1201085. PMID   9188854. S2CID   26359262.
13. Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A, Trouche D (Sep 1998). "The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase". Proceedings of the National Academy of Sciences of the United States of America. 95 (18): 10493–8. Bibcode:1998PNAS...9510493F. doi: 10.1073/pnas.95.18.10493 . PMC   27922 . PMID   9724731.
14. Bouzahzah B, Fu M, Iavarone A, Factor VM, Thorgeirsson SS, Pestell RG (Aug 2000). "Transforming growth factor-beta1 recruits histone deacetylase 1 to a p130 repressor complex in transgenic mice in vivo". Cancer Research. 60 (16): 4531–7. PMID   10969803.
15. Wang S, Nath N, Adlam M, Chellappan S (Jun 1999). "Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function". Oncogene. 18 (23): 3501–10. doi:10.1038/sj.onc.1202684. PMID   10376528. S2CID   33828482.
16. Meloni AR, Smith EJ, Nevins JR (Aug 1999). "A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor". Proceedings of the National Academy of Sciences of the United States of America. 96 (17): 9574–9. Bibcode:1999PNAS...96.9574M. doi: 10.1073/pnas.96.17.9574 . PMC   22250 . PMID   10449734.
17. Fusco C, Reymond A, Zervos AS (Aug 1998). "Molecular cloning and characterization of a novel retinoblastoma-binding protein". Genomics. 51 (3): 351–8. doi:10.1006/geno.1998.5368. PMID   9721205.
18. Aughey GN, Cali E, Maroofian R, Zaki MS, Pagnamenta AT, Ali Z, Abdulllah U, Rahman F, Menzies L, Shafique A, Suri M, Roze E, Aguennouz M, Ghizlane Z, Saadi SM (2024-12-18). "Clinical and genetic characterization of a progressive RBL2 -associated neurodevelopmental disorder". Brain. doi:10.1093/brain/awae363. ISSN   0006-8950.
19. Brunet T, Radivojkov-Blagojevic M, Lichtner P, Kraus V, Meitinger T, Wagner M (March 2020). "Biallelic loss‐of‐function variants in RBL2 in siblings with a neurodevelopmental disorder". Annals of Clinical and Translational Neurology. 7 (3): 390–396. doi:10.1002/acn3.50992. ISSN   2328-9503. PMC   7086002 . PMID   32105419.
20. Samra N, Toubiana S, Yttervik H, Tzur-Gilat A, Morani I, Itzkovich C, Giladi L, Abu Jabal K, Cao JZ, Godley LA, Mory A, Baris Feldman H, Tveten K, Selig S, Weiss K (November 2021). "RBL2 bi-allelic truncating variants cause severe motor and cognitive impairment without evidence for abnormalities in DNA methylation or telomeric function". Journal of Human Genetics. 66 (11): 1101–1112. doi:10.1038/s10038-021-00931-z. ISSN   1434-5161.

Further reading

• Soprano KJ, Purev E, Vuocolo S, Soprano DR (Aug 2006). "Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid". Oncogene. 25 (38): 5315–25. doi:10.1038/sj.onc.1209679. PMID   16936753. S2CID   19893445.
• De Falco G, Giordano A (Aug 2006). "pRb2/p130: a new candidate for retinoblastoma tumor formation". Oncogene. 25 (38): 5333–40. doi:10.1038/sj.onc.1209614. PMID   16936755. S2CID   40396708.
• Hijmans EM, Voorhoeve PM, Beijersbergen RL, van 't Veer LJ, Bernards R (Jun 1995). "E2F-5, a new E2F family member that interacts with p130 in vivo". Molecular and Cellular Biology. 15 (6): 3082–9. doi:10.1128/mcb.15.6.3082. PMC   230539 . PMID   7760804.
• Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg RA (Mar 1995). "E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle". Proceedings of the National Academy of Sciences of the United States of America. 92 (6): 2403–7. Bibcode:1995PNAS...92.2403S. doi: 10.1073/pnas.92.6.2403 . PMC   42492 . PMID   7892279.
• Yeung RS, Bell DW, Testa JR, Mayol X, Baldi A, Graña X, Klinga-Levan K, Knudson AG, Giordano A (Dec 1993). "The retinoblastoma-related gene, RB2, maps to human chromosome 16q12 and rat chromosome 19". Oncogene. 8 (12): 3465–8. PMID   8247552.
• Li Y, Graham C, Lacy S, Duncan AM, Whyte P (Dec 1993). "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". Genes & Development. 7 (12A): 2366–77. doi: 10.1101/gad.7.12a.2366 . PMID   8253383.
• Hannon GJ, Demetrick D, Beach D (Dec 1993). "Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins". Genes & Development. 7 (12A): 2378–91. doi: 10.1101/gad.7.12a.2378 . PMID   8253384.
• Lavender P, Vandel L, Bannister AJ, Kouzarides T (Jun 1997). "The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A". Oncogene. 14 (22): 2721–8. doi: 10.1038/sj.onc.1201243 . PMID   9178770.
• Lacy S, Whyte P (May 1997). "Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes". Oncogene. 14 (20): 2395–406. doi:10.1038/sj.onc.1201085. PMID   9188854. S2CID   26359262.
• Shao Z, Siegert JL, Ruppert S, Robbins PD (Jul 1997). "Rb interacts with TAF(II)250/TFIID through multiple domains". Oncogene. 15 (4): 385–92. doi: 10.1038/sj.onc.1201204 . PMID   9242374.
• Sterner JM, Dew-Knight S, Musahl C, Kornbluth S, Horowitz JM (May 1998). "Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7". Molecular and Cellular Biology. 18 (5): 2748–57. doi:10.1128/mcb.18.5.2748. PMC   110654 . PMID   9566894.
• Woitach JT, Zhang M, Niu CH, Thorgeirsson SS (Aug 1998). "A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability". Nature Genetics. 19 (4): 371–4. doi:10.1038/1258. PMID   9697699. S2CID   11374970.
• Veal E, Eisenstein M, Tseng ZH, Gill G (Sep 1998). "A cellular repressor of E1A-stimulated genes that inhibits activation by E2F". Molecular and Cellular Biology. 18 (9): 5032–41. doi:10.1128/mcb.18.9.5032. PMC   109088 . PMID   9710587.
• Fusco C, Reymond A, Zervos AS (Aug 1998). "Molecular cloning and characterization of a novel retinoblastoma-binding protein". Genomics. 51 (3): 351–8. doi:10.1006/geno.1998.5368. PMID   9721205.
• Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A, Trouche D (Sep 1998). "The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase". Proceedings of the National Academy of Sciences of the United States of America. 95 (18): 10493–8. Bibcode:1998PNAS...9510493F. doi: 10.1073/pnas.95.18.10493 . PMC   27922 . PMID   9724731.
• Paramio JM, Laín S, Segrelles C, Lane EB, Jorcano JL (Aug 1998). "Differential expression and functionally co-operative roles for the retinoblastoma family of proteins in epidermal differentiation". Oncogene. 17 (8): 949–57. doi: 10.1038/sj.onc.1202031 . PMID   9747874. S2CID   21804961.
• Wang S, Ghosh RN, Chellappan SP (Dec 1998). "Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation". Molecular and Cellular Biology. 18 (12): 7487–98. doi:10.1128/mcb.18.12.7487. PMC   109329 . PMID   9819434.
• Yang R, Müller C, Huynh V, Fung YK, Yee AS, Koeffler HP (Mar 1999). "Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins". Molecular and Cellular Biology. 19 (3): 2400–7. doi:10.1128/mcb.19.3.2400. PMC   84032 . PMID   10022926.

External links

• RBL2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.