RBBP8 (retinoblastoma binding protein 8)

2008-05-01 Govindaswamy Chinnadurai , Thirugnana Subramanian , Selvamani Vijayalingam Affiliation

Institute for Molecular, Virology, Saint Louis University School of Medicine, Doisy Research Center, 1100 South Grand Blvd, St. Louis, Missouri 63104, USA

Identity

HGNC

RBBP8

LOCATION

18q11.2

LOCUSID

5932

ALIAS

COM1,CTIP,JWDS,RIM,SAE2,SCKL2

FUSION GENES

Show Gene Fusions

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

Predominantly localized in the nucleus; contains 4 potential nuclear localization signals and two leucine zipper motifs, a Rb binding domain, a CtBP binding motif, a coiled-coil domain, two CXXC motifs similar to the Zn-hook motif of Rad50.

Function

Potential modulator of BRCA1 in transcriptional regulation, DNA repair and cell cycle checkpoint control.
Family: ezrin/radixin/myosin family
Category: regulatory, transcription factor, antioncogene
Interaction: binds to Rb, CtBP, BRCA1, LMO4, SIAH1, Ikaros, MRE11 complex.

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).

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

Gene ID	Transcript ID	Uniprot
ENSG00000101773	ENST00000327155	Q99708
ENSG00000101773	ENST00000327155	A0A024RC34
ENSG00000101773	ENST00000360790	I6L8A6
ENSG00000101773	ENST00000399721	F6Q6H0
ENSG00000101773	ENST00000399722	Q99708
ENSG00000101773	ENST00000399722	A0A024RC34
ENSG00000101773	ENST00000399725	Q99708
ENSG00000101773	ENST00000577445	J3QL00
ENSG00000101773	ENST00000577588	J3QRM0
ENSG00000101773	ENST00000579124	J3KSA4
ENSG00000101773	ENST00000581687	J3QLH2
ENSG00000101773	ENST00000581819	J3QL93
ENSG00000101773	ENST00000582354	J3QLW6
ENSG00000101773	ENST00000583057	J3QSH7
ENSG00000101773	ENST00000583700	A0A140TA82
ENSG00000101773	ENST00000585177	V9GZ40

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Homologous recombination	KEGG	ko03440
Homologous recombination	KEGG	hsa03440
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
Cell Cycle	REACTOME	R-HSA-1640170
Cell Cycle Checkpoints	REACTOME	R-HSA-69620
G2/M Checkpoints	REACTOME	R-HSA-69481
G2/M DNA damage checkpoint	REACTOME	R-HSA-69473
Meiosis	REACTOME	R-HSA-1500620
Meiotic recombination	REACTOME	R-HSA-912446
DNA Repair	REACTOME	R-HSA-73894
DNA Double-Strand Break Repair	REACTOME	R-HSA-5693532
Homology Directed Repair	REACTOME	R-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)	REACTOME	R-HSA-5693567
Processing of DNA double-strand break ends	REACTOME	R-HSA-5693607
HDR through Homologous Recombination (HRR)	REACTOME	R-HSA-5685942
Homologous DNA Pairing and Strand Exchange	REACTOME	R-HSA-5693579
Presynaptic phase of homologous DNA pairing and strand exchange	REACTOME	R-HSA-5693616
Resolution of D-Loop Structures	REACTOME	R-HSA-5693537
Resolution of D-loop Structures through Holliday Junction Intermediates	REACTOME	R-HSA-5693568
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	REACTOME	R-HSA-5693554
HDR through Single Strand Annealing (SSA)	REACTOME	R-HSA-5685938
HDR through MMEJ (alt-NHEJ)	REACTOME	R-HSA-5685939
Regulation of TP53 Activity	REACTOME	R-HSA-5633007
Regulation of TP53 Activity through Phosphorylation	REACTOME	R-HSA-6804756

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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-(retinoblastoma-binding-protein-8)