RBBP8 (retinoblastoma binding protein 8)
2008-05-01 Govindaswamy Chinnadurai , Thirugnana Subramanian , Selvamani Vijayalingam AffiliationInstitute for Molecular, Virology, Saint Louis University School of Medicine, Doisy Research Center, 1100 South Grand Blvd, St. Louis, Missouri 63104, USA
Identity
HGNC
LOCATION
18q11.2
LOCUSID
ALIAS
COM1,CTIP,JWDS,RIM,SAE2,SCKL2
FUSION GENES
DNA/RNA
Description
The gene encompasses 93.155 Kb of DNA.
Transcription
3279 bp mRNA.
Proteins
Domain structure of hCtIP. All known CtIP proteins contain a highly conserved CtBP-binding motif, two CXXC motifs and a phosphorylation site that corresponds to Ser327 in hCtIP. The Rb-binding motif is conserved only in mammalian CtIP. The N-terminal and C-terminal regions of all the CtIP homologs show high degrees of conservation. The ATM target site that corresponds to Ser664 is not conserved in CtIP of certain species (e.g., mouse and chicken). The A9 repeat, a tumor-specific nucleotide polymorphism (G2115A) and a nucleotide polymorphism (G1766A) resulting in an amino acid substitution (K589H) observed in tumor and normal cells are indicated. The region between amino acid positions 45 to 160 is a coiled-coil. A C-terminal region conserved between CtIPs and the plant (Arabidopsis thaliana) gamma response 1 (AtGR1) protein is also indicated (light blue).
Description
897 a.a. polypeptide.
Expression
Widely expressed in various human tissues - thymus and testis appear to express the highest levels.
Localisation
Function
Homology
Homolog to C.elegans r05d3.4, fission yeast Ctp1. CtIP is conserved among vertebrates. A C-terminal domain of CtIP is homologous to plant gamma response 1(AtGR1) protein of Arabidopsis thaliana.
Variant: CtIP splice variant (Genebank Accession # NP_976037) with 867 a.a. is identical to CtIP except the C-terminal region (a.a. 786-867).
Variant: CtIP splice variant (Genebank Accession # NP_976037) with 867 a.a. is identical to CtIP except the C-terminal region (a.a. 786-867).
Mutations
Germinal
Knockout mice experiment has shown that inactivation of both CtIP alleles resulted in early embryonic lethality at stage E4. However the heterozygous CtIP+/- mice were viable with reduced life span due to development of multiple tumors.
Somatic
A number of human tumor cell lines derived from various tissues did not detect any homozygous deletion within the CtIP gene. However, some missense and silent mutations have been reported.
Implicated in
Entity name
Tumors
Disease
Recent studies with mutant mice have raised the possibility that Ctip might be a tumor suppressor gene. Inactivation of both Ctip alleles results in early embryonic lethality at stage E4. However, the heterozygous Ctip+/- mice are viable, but the life span is reduced compared to Ctip+/+ animals due to the development of multiple tumors. Among the types of tumors observed in Ctip+/- animals, B and T cell lymphomas (B-NHL and T-NHL) are most prevalent. Enhanced lymphoid specificity of tumorigenesis might reflect the fact that these tissues are active sites of DNA repair and CtIP insufficiency might contribute to lymphoma development due to potential defects in DNA repair.
Oncogenesis
Since CtIP seems to be very important for the activities of tumor suppressors such as BRCA1, pRb family and Ikaros family, CtIP may be a tumor suppressor protein.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15831459 | 2005 | Inactivation of CtIP leads to early embryonic lethality mediated by G1 restraint and to tumorigenesis by haploid insufficiency. | Chen PL et al |
| 16249056 | 2006 | CtIP, a candidate tumor susceptibility gene is a team player with luminaries. | Chinnadurai G et al |
| 9721205 | 1998 | Molecular cloning and characterization of a novel retinoblastoma-binding protein. | Fusco C et al |
| 10196224 | 1999 | Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage. | Li S et al |
| 17936710 | 2007 | Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination. | Limbo O et al |
| 17965729 | 2007 | Human CtIP promotes DNA end resection. | Sartori AA et al |
| 9535825 | 1998 | Interaction between a cellular protein that binds to the C-terminal region of adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A through a conserved PLDLS motif. | Schaeper U et al |
| 9811458 | 1998 | Characterization of a carboxy-terminal BRCA1 interacting protein. | Wong AK et al |
| 10764811 | 2000 | Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor. | Yu X et al |
| 9738006 | 1998 | The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression. | Yu X et al |
Other Information
Locus ID:
NCBI: 5932
MIM: 604124
HGNC: 9891
Ensembl: ENSG00000101773
Variants:
dbSNP: 5932
ClinVar: 5932
TCGA: ENSG00000101773
COSMIC: RBBP8
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38324469 | 2024 | NUDT16 regulates CtIP PARylation to dictate homologous recombination repair. | 0 |
| 38324469 | 2024 | NUDT16 regulates CtIP PARylation to dictate homologous recombination repair. | 0 |
| 35106666 | 2023 | Prognostic Significance of mRNA Expression RBBP8 or Its Methylation in Gliomas. | 1 |
| 37615686 | 2023 | A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome. | 0 |
| 35106666 | 2023 | Prognostic Significance of mRNA Expression RBBP8 or Its Methylation in Gliomas. | 1 |
| 37615686 | 2023 | A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome. | 0 |
| 35203293 | 2022 | RNAi Screening Uncovers a Synthetic Sick Interaction between CtIP and the BARD1 Tumor Suppressor. | 0 |
| 35414773 | 2022 | IKZF1 selectively enhances homologous recombination repair by interacting with CtIP and USP7 in multiple myeloma. | 2 |
| 36010636 | 2022 | The Ubiquitin Ligase RNF138 Cooperates with CtIP to Stimulate Resection of Complex DNA Double-Strand Breaks in Human G1-Phase Cells. | 1 |
| 36155803 | 2022 | SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination. | 6 |
| 36172813 | 2022 | The mechanism of radiotherapy for lung adenocarcinoma in promoting protein SIRT6-mediated deacetylation of RBBP8 to enhance the sensitivity of targeted therapy. | 2 |
| 35203293 | 2022 | RNAi Screening Uncovers a Synthetic Sick Interaction between CtIP and the BARD1 Tumor Suppressor. | 0 |
| 35414773 | 2022 | IKZF1 selectively enhances homologous recombination repair by interacting with CtIP and USP7 in multiple myeloma. | 2 |
| 36010636 | 2022 | The Ubiquitin Ligase RNF138 Cooperates with CtIP to Stimulate Resection of Complex DNA Double-Strand Breaks in Human G1-Phase Cells. | 1 |
| 36155803 | 2022 | SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination. | 6 |
Citation
Govindaswamy Chinnadurai ; Thirugnana Subramanian ; Selvamani Vijayalingam
RBBP8 (retinoblastoma binding protein 8)
Atlas Genet Cytogenet Oncol Haematol. 2008-05-01
Online version: http://atlasgeneticsoncology.org/gene/42066/rbbp8
