RBBP7 (retinoblastoma binding protein 7)
2009-07-01 Neehar Sinha , Ranjan Tamuli AffiliationDepartment of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India
Identity
HGNC
LOCATION
Xp22.2
LOCUSID
ALIAS
RBAP46,RbAp46,RBBP-7,MGC138867,MGC138868
FUSION GENES
DNA/RNA
Description
DNA size 27.75 kb; mRNA size 2021 bp; 12 exons.
Proteins
Description
425 amino acids; 47.82 kDa protein.
Post translational modifications: Phosphorylation enhances DNA binding. Phosphorylation occurs at position 95, 99, 354, 413 (Serine) and 416 (Threonine). Acetylation brings in a negative charge, acting to neutralise the positive charge on the histones and decreases the interaction of the N termini of histones with the negatively charged phosphate groups of DNA. As a consequence, the condensed chromatin is transformed into a more relaxed structure which is associated with greater levels of gene transcription.
The acetylation sites are: at 2 (Alanine), and 119 (Lysine).
Isoform: The following isoforms have been identified:
- RBBP7.iApr07
- hPA25320.1 (469 aa)
- hPA25320.2 (425 aa)
- hPA25320.3 (410 aa)
- hPA25320.7 (420 aa)
Expression
It is widely expressed.
Localisation
Nucleus.
Function
This protein is an ubiquitously expressed nuclear protein and it belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly, which include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodelling. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation.
Homology
The percent identity below represents identity of RBBP7 over an aligned region in UniGene.
- M. musculus : 100 (percentage identity)
- C. lupus familiaris : 100
- B. taurus : 100
- R. norvegicus : 100
- G.gallus : 96.2
- D. rerio : 94.4
- M. musculus : 100 (percentage identity)
- C. lupus familiaris : 100
- B. taurus : 100
- R. norvegicus : 100
- G.gallus : 96.2
- D. rerio : 94.4
Mutations
Note
Two types of mutation have been detected in the RBBP7 gene. A827G is a silent mutation and the other one is a missense type of mutation that changes N276S.
Implicated in
Entity name
Breast cancer
Note
RBBP7 (also known as RbAp46) overexpression has shown to inhibit the tumorigenicity of neoplastigenic breast epithelial cells (Li et al., 2003). RBBP7 activates stress-induced apoptosis, the JNK-dependent apoptotic cell death, possibly through upregulation of GADD45 (Growth arrest- and DNA damage-inducible 45). GADD45 binds and activates MAPKKK MTK1/MEK4, the upstream regulator of JNK, triggering JNK-dependent apoptosis. Thus, overexpression of RBBP7 facilitates stress-induced apoptosis and suppresses tumorigenicity of neoplastigenic breast epithelial cells.
Entity name
Leukemia
Note
Expression level of RBBP7 in initial acute leukemia has been found to be significantly higher than in chronic myelogenous leukemia. The Wilms tumor suppressor gene (WT1) expression level was also correlated with RBBP7 expression. WT1 encodes a zinc finger transcription factor that regulates transcription of its downstream gene. RBBP7 is a downstream effector of WT1 gene, and acts in a similar manner as WT1 does. It has been seen that high expression of RBBP7 suppresses the tumorigenicity of neoplastic breast epithelial cells but its overexpression possibly may induce leukemia. This phenomenon suggests that the regulatory pathway for RbAp46 gene expression in acute leukemia may be different from that in solid tumor.
Entity name
Human embryonic kidney (HEK) 293 cell tumorigenesis
Note
High levels of RbAp46 suppress the tumorigenicity of adenovirus-transformed human embryonic kidney 293 cells. High level of RbAp46 resulted in G2/M cell population and augmented apoptosis in serum starved cells. It is possible that overexpression of RbAp46 may interfere with normal cell cycle and/or enhance apoptotic cell death which inhibits the transformation of tumor cells.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12513776 | 2002 | [WT1-mediated pathway of transcriptional regulation and leukemia]. | Duan WM et al |
| 11433396 | 2001 | Rb-associated protein 46 (RbAp46) suppresses the tumorigenicity of adenovirus-transformed human embryonic kidney 293 cells. | Guan LS et al |
| 16117885 | 2005 | High expression of RbAp46 gene in patients with acute leukemia or chronic myelogenous leukemia in blast crisis. | Hu SY et al |
| 12767060 | 2003 | Overexpression of RbAp46 facilitates stress-induced apoptosis and suppresses tumorigenicity of neoplastigenic breast epithelial cells. | Li GC et al |
| 17201172 | 2006 | Retinoblastoma suppressor associated protein 46 (RbAp46) attenuates the beta-catenin/TCF signaling through up-regulation of GSK-3beta expression. | Li GC et al |
| 18500265 | 2008 | Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas. | Têtu B et al |
| 17314274 | 2007 | Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer. | Thakur A et al |
| 17970062 | 2007 | RbAp46 inhibits estrogen-stimulated progression of neoplastigenic breast epithelial cells. | Zhang TF et al |
| 15921624 | 2005 | [Expressive profile of retinoblastoma-associated protein 46 and its clinical significance in acute leukemias]. | Zhou JC et al |
Other Information
Locus ID:
NCBI: 5931
MIM: 300825
HGNC: 9890
Ensembl: ENSG00000102054
Variants:
dbSNP: 5931
ClinVar: 5931
TCGA: ENSG00000102054
COSMIC: RBBP7
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38368381 | 2024 | RBBP7, regulated by SP1, enhances the Warburg effect to facilitate the proliferation of hepatocellular carcinoma cells via PI3K/AKT signaling. | 0 |
| 38577935 | 2024 | Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review). | 0 |
| 38368381 | 2024 | RBBP7, regulated by SP1, enhances the Warburg effect to facilitate the proliferation of hepatocellular carcinoma cells via PI3K/AKT signaling. | 0 |
| 38577935 | 2024 | Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review). | 0 |
| 37225855 | 2023 | FIT links c-Myc and P53 acetylation by recruiting RBBP7 during colorectal carcinogenesis. | 2 |
| 37843278 | 2023 | X-linked RBBP7 mutation causes maturation arrest and testicular tumors. | 1 |
| 37225855 | 2023 | FIT links c-Myc and P53 acetylation by recruiting RBBP7 during colorectal carcinogenesis. | 2 |
| 37843278 | 2023 | X-linked RBBP7 mutation causes maturation arrest and testicular tumors. | 1 |
| 34709113 | 2022 | Overlapping functions of RBBP4 and RBBP7 in regulating cell proliferation and histone H3.3 deposition during mouse preimplantation development. | 10 |
| 35538026 | 2022 | Hypoxia-induced RBBP7 promotes esophagus cancer progression by inducing CDK4 expression. | 6 |
| 34709113 | 2022 | Overlapping functions of RBBP4 and RBBP7 in regulating cell proliferation and histone H3.3 deposition during mouse preimplantation development. | 10 |
| 35538026 | 2022 | Hypoxia-induced RBBP7 promotes esophagus cancer progression by inducing CDK4 expression. | 6 |
| 31957828 | 2020 | Circular RNA hsa_circ_0006168 contributes to cell proliferation, migration and invasion in esophageal cancer by regulating miR-384/RBBP7 axis via activation of S6K/S6 pathway. | 16 |
| 31957828 | 2020 | Circular RNA hsa_circ_0006168 contributes to cell proliferation, migration and invasion in esophageal cancer by regulating miR-384/RBBP7 axis via activation of S6K/S6 pathway. | 16 |
| 29263092 | 2018 | Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epigenetic complexes. | 32 |
Citation
Neehar Sinha ; Ranjan Tamuli
RBBP7 (retinoblastoma binding protein 7)
Atlas Genet Cytogenet Oncol Haematol. 2009-07-01
Online version: http://atlasgeneticsoncology.org/gene/42065/rbbp7
