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RBBP8 (retinoblastoma binding protein 8)

Written2008-05Govindaswamy Chinnadurai, Thirugnana Subramanian, Selvamani Vijayalingam
Institute for Molecular, Virology, Saint Louis University School of Medicine, Doisy Research Center, 1100 South Grand Blvd, St. Louis, Missouri 63104, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSCKL2
retinoblastoma-binding protein 8
Seckel syndrome 2
retinoblastoma binding protein 8
Alias_symbol (synonym)CtIP
RIM
COM1
Other aliasCTIP
HGNC (Hugo) RBBP8
LocusID (NCBI) 5932
Atlas_Id 42066
Location 18q11.2  [Link to chromosome band 18q11]
Location_base_pair Starts at 22933332 and ends at 23026486 bp from pter ( according to hg19-Feb_2009)  [Mapping RBBP8.png]
Fusion genes
(updated 2016)
ATXN2 (12q24.12) / RBBP8 (18q11.2)CABLES1 (18q11.2) / RBBP8 (18q11.2)FERMT1 (20p12.3) / RBBP8 (18q11.2)
LAMA3 (18q11.2) / RBBP8 (18q11.2)RBBP8 (18q11.2) / ANXA4 (2p13.3)RBBP8 (18q11.2) / FAM126A (7p15.3)
RBBP8 (18q11.2) / RBBP8 (18q11.2)RBBP8 (18q11.2) / STK24 (13q32.2)RBBP8 (18q11.2) / TAF4B (18q11.2)
RBBP8 (18q11.2) / TP53 (17p13.1)

DNA/RNA

 
Description The gene encompasses 93.155 Kb of DNA.
Transcription 3279 bp mRNA.

Protein

 
  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

Note
  
Entity 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.
  

Bibliography

Inactivation of CtIP leads to early embryonic lethality mediated by G1 restraint and to tumorigenesis by haploid insufficiency.
Chen PL, Liu F, Cai S, Lin X, Li A, Chen Y, Gu B, Lee EY, Lee WH.
Mol Cell Biol. 2005 May;25(9):3535-42.
PMID 15831459
 
CtIP, a candidate tumor susceptibility gene is a team player with luminaries.
Chinnadurai G.
Biochim Biophys Acta. 2006 Jan;1765(1):67-73. Epub 2005 Oct 6.
PMID 16249056
 
Molecular cloning and characterization of a novel retinoblastoma-binding protein.
Fusco C, Reymond A, Zervos AS.
Genomics. 1998 Aug 1;51(3):351-8.
PMID 9721205
 
Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage.
Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH.
J Biol Chem. 1999 Apr 16;274(16):11334-8.
PMID 10196224
 
Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination.
Limbo O, Chahwan C, Yamada Y, de Bruin RA, Wittenberg C, Russell P.
Mol Cell. 2007 Oct 12;28(1):134-46.
PMID 17936710
 
Human CtIP promotes DNA end resection.
Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP.
Nature. 2007 Nov 22;450(7169):509-14. Epub 2007 Oct 28.
PMID 17965729
 
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, Subramanian T, Lim L, Boyd JM, Chinnadurai G.
J Biol Chem. 1998 Apr 10;273(15):8549-52.
PMID 9535825
 
Characterization of a carboxy-terminal BRCA1 interacting protein.
Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G, Berry S, Lawrence Q, Dayananth P, Ha P, Tavtigian SV, Teng DH, Bartel PL.
Oncogene. 1998 Nov 5;17(18):2279-85.
PMID 9811458
 
Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor.
Yu X, Baer R.
J Biol Chem. 2000 Jun 16;275(24):18541-9.
PMID 10764811
 
The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression.
Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R.
J Biol Chem. 1998 Sep 25;273(39):25388-92.
PMID 9738006
 

Citation

This paper should be referenced as such :
Chinnadurai, G ; Subramanian, T ; Vijayalingam, S
RBBP8 (retinoblastoma binding protein 8)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(4):282-284.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RBBP8ID42066ch18q11.html


External links

Nomenclature
HGNC (Hugo)RBBP8   9891
Cards
AtlasRBBP8ID42066ch18q11
Entrez_Gene (NCBI)RBBP8  5932  RB binding protein 8, endonuclease
AliasesCOM1; CTIP; JWDS; RIM; 
SAE2; SCKL2
GeneCards (Weizmann)RBBP8
Ensembl hg19 (Hinxton)ENSG00000101773 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000101773 [Gene_View]  chr18:22933332-23026486 [Contig_View]  RBBP8 [Vega]
ICGC DataPortalENSG00000101773
TCGA cBioPortalRBBP8
AceView (NCBI)RBBP8
Genatlas (Paris)RBBP8
WikiGenes5932
SOURCE (Princeton)RBBP8
Genetics Home Reference (NIH)RBBP8
Genomic and cartography
GoldenPath hg38 (UCSC)RBBP8  -     chr18:22933332-23026486 +  18q11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RBBP8  -     18q11.2   [Description]    (hg19-Feb_2009)
EnsemblRBBP8 - 18q11.2 [CytoView hg19]  RBBP8 - 18q11.2 [CytoView hg38]
Mapping of homologs : NCBIRBBP8 [Mapview hg19]  RBBP8 [Mapview hg38]
OMIM251255   604124   606744   
Gene and transcription
Genbank (Entrez)AF043431 AK292481 BC001170 BC030590 BG723261
RefSeq transcript (Entrez)NM_002894 NM_203291 NM_203292
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RBBP8
Cluster EST : UnigeneHs.546282 [ NCBI ]
CGAP (NCI)Hs.546282
Alternative Splicing GalleryENSG00000101773
Gene ExpressionRBBP8 [ NCBI-GEO ]   RBBP8 [ EBI - ARRAY_EXPRESS ]   RBBP8 [ SEEK ]   RBBP8 [ MEM ]
Gene Expression Viewer (FireBrowse)RBBP8 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5932
GTEX Portal (Tissue expression)RBBP8
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99708   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ99708  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ99708
Splice isoforms : SwissVarQ99708
Catalytic activity : Enzyme3.1.-.- [ Enzyme-Expasy ]   3.1.-.-3.1.-.- [ IntEnz-EBI ]   3.1.-.- [ BRENDA ]   3.1.-.- [ KEGG ]   
PhosPhoSitePlusQ99708
Domains : Interpro (EBI)CtIP_N    Ctp1_C    RBBP8    RBBP8-like   
Domain families : Pfam (Sanger)CtIP_N (PF10482)    SAE2 (PF08573)   
Domain families : Pfam (NCBI)pfam10482    pfam08573   
Conserved Domain (NCBI)RBBP8
DMDM Disease mutations5932
Blocks (Seattle)RBBP8
PDB (SRS)2L4Z    4D2H   
PDB (PDBSum)2L4Z    4D2H   
PDB (IMB)2L4Z    4D2H   
PDB (RSDB)2L4Z    4D2H   
Structural Biology KnowledgeBase2L4Z    4D2H   
SCOP (Structural Classification of Proteins)2L4Z    4D2H   
CATH (Classification of proteins structures)2L4Z    4D2H   
SuperfamilyQ99708
Human Protein AtlasENSG00000101773
Peptide AtlasQ99708
HPRD04990
IPIIPI00480111   IPI00304023   IPI00402159   
Protein Interaction databases
DIP (DOE-UCLA)Q99708
IntAct (EBI)Q99708
FunCoupENSG00000101773
BioGRIDRBBP8
STRING (EMBL)RBBP8
ZODIACRBBP8
Ontologies - Pathways
QuickGOQ99708
Ontology : AmiGOsingle-stranded DNA endodeoxyribonuclease activity  cell cycle checkpoint  G1/S transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  double-strand break repair via homologous recombination  double-strand break repair via homologous recombination  DNA double-strand break processing  DNA synthesis involved in DNA repair  strand displacement  RNA polymerase II repressing transcription factor binding  RNA polymerase II transcription corepressor activity  blastocyst hatching  damaged DNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  chromosome  DNA replication  DNA repair  nucleotide-excision repair  regulation of transcription from RNA polymerase II promoter  DNA double-strand break processing involved in repair via single-strand annealing  transcriptional repressor complex  G2 DNA damage checkpoint  response to estradiol  intracellular membrane-bounded organelle  cell division  meiotic cell cycle  nucleic acid phosphodiester bond hydrolysis  regulation of signal transduction by p53 class mediator  
Ontology : EGO-EBIsingle-stranded DNA endodeoxyribonuclease activity  cell cycle checkpoint  G1/S transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  double-strand break repair via homologous recombination  double-strand break repair via homologous recombination  DNA double-strand break processing  DNA synthesis involved in DNA repair  strand displacement  RNA polymerase II repressing transcription factor binding  RNA polymerase II transcription corepressor activity  blastocyst hatching  damaged DNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  chromosome  DNA replication  DNA repair  nucleotide-excision repair  regulation of transcription from RNA polymerase II promoter  DNA double-strand break processing involved in repair via single-strand annealing  transcriptional repressor complex  G2 DNA damage checkpoint  response to estradiol  intracellular membrane-bounded organelle  cell division  meiotic cell cycle  nucleic acid phosphodiester bond hydrolysis  regulation of signal transduction by p53 class mediator  
Pathways : BIOCARTAATM Signaling Pathway [Genes]   
REACTOMEQ99708 [protein]
REACTOME PathwaysR-HSA-912446 [pathway]   
NDEx NetworkRBBP8
Atlas of Cancer Signalling NetworkRBBP8
Wikipedia pathwaysRBBP8
Orthology - Evolution
OrthoDB5932
GeneTree (enSembl)ENSG00000101773
Phylogenetic Trees/Animal Genes : TreeFamRBBP8
HOVERGENQ99708
HOGENOMQ99708
Homologs : HomoloGeneRBBP8
Homology/Alignments : Family Browser (UCSC)RBBP8
Gene fusions - Rearrangements
Fusion : MitelmanCABLES1/RBBP8 [18q11.2/18q11.2]  [t(18;18)(q11;q11)]  
Fusion : MitelmanFERMT1/RBBP8 [20p12.3/18q11.2]  [t(18;20)(q11;p12)]  
Fusion : MitelmanRBBP8/ANXA4 [18q11.2/2p13.3]  [t(2;18)(p13;q11)]  
Fusion : MitelmanRBBP8/FAM126A [18q11.2/7p15.3]  [t(7;18)(p15;q11)]  
Fusion : MitelmanRBBP8/TAF4B [18q11.2/18q11.2]  [t(18;18)(q11;q11)]  
Fusion : MitelmanRBBP8/TP53 [18q11.2/17p13.1]  [t(17;18)(p13;q11)]  
Fusion: TCGACABLES1 18q11.2 RBBP8 18q11.2 BRCA
Fusion: TCGAFERMT1 20p12.3 RBBP8 18q11.2 BRCA
Fusion: TCGARBBP8 18q11.2 ANXA4 2p13.3 LUSC
Fusion: TCGARBBP8 18q11.2 FAM126A 7p15.3 LGG
Fusion: TCGARBBP8 18q11.2 TAF4B 18q11.2 HNSC
Fusion: TCGARBBP8 18q11.2 TP53 17p13.1 BLCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRBBP8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RBBP8
dbVarRBBP8
ClinVarRBBP8
1000_GenomesRBBP8 
Exome Variant ServerRBBP8
ExAC (Exome Aggregation Consortium)RBBP8 (select the gene name)
Genetic variants : HAPMAP5932
Genomic Variants (DGV)RBBP8 [DGVbeta]
DECIPHERRBBP8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRBBP8 
Mutations
ICGC Data PortalRBBP8 
TCGA Data PortalRBBP8 
Broad Tumor PortalRBBP8
OASIS PortalRBBP8 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRBBP8  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRBBP8
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RBBP8
DgiDB (Drug Gene Interaction Database)RBBP8
DoCM (Curated mutations)RBBP8 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RBBP8 (select a term)
intoGenRBBP8
NCG5 (London)RBBP8
Cancer3DRBBP8(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM251255    604124    606744   
Orphanet954    21451   
MedgenRBBP8
Genetic Testing Registry RBBP8
NextProtQ99708 [Medical]
TSGene5932
GENETestsRBBP8
Target ValidationRBBP8
Huge Navigator RBBP8 [HugePedia]
snp3D : Map Gene to Disease5932
BioCentury BCIQRBBP8
ClinGenRBBP8
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5932
Chemical/Pharm GKB GenePA34255
Clinical trialRBBP8
Miscellaneous
canSAR (ICR)RBBP8 (select the gene name)
Probes
Litterature
PubMed120 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRBBP8
EVEXRBBP8
GoPubMedRBBP8
iHOPRBBP8
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jun 7 12:13:09 CEST 2017

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