RBBP8 (retinoblastoma binding protein 8)

Identity

Other names	CTIP
	RIM
HGNC	RBBP8
Location	18q11.2

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

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.

External links

	Nomenclature
HGNC	RBBP8   9891
Entrez_Gene	RBBP8  5932  retinoblastoma binding protein 8
	Cards
Atlas	RBBP8ID42066ch18q11
GeneCards	RBBP8
Ensembl	RBBP8 [Search_View]   ENSG00000101773 [Gene_View]
Genatlas	RBBP8
GeneLynx	RBBP8
eGenome	RBBP8
euGene	5932
	Genomic and cartography
GoldenPath	RBBP8  -  18q11.2   chr18:18767293-18860447 +  18q11.2   [Description]    (hg18-Mar_2006)
Ensembl	RBBP8 - 18q11.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	RBBP8
	Gene and transcription
Genbank	AF043431 [ ENTREZ ]
Genbank	AK292481 [ ENTREZ ]
Genbank	BC001170 [ ENTREZ ]
Genbank	BC030590 [ ENTREZ ]
Genbank	BG723261 [ ENTREZ ]
RefSeq	NM_002894 [ SRS ]    NM_002894 [ ENTREZ ]
RefSeq	NM_203291 [ SRS ]    NM_203291 [ ENTREZ ]
RefSeq	NM_203292 [ SRS ]    NM_203292 [ ENTREZ ]
RefSeq	AC_000061 [ SRS ]    AC_000061 [ ENTREZ ]
RefSeq	AC_000150 [ SRS ]    AC_000150 [ ENTREZ ]
RefSeq	NC_000018 [ SRS ]    NC_000018 [ ENTREZ ]
RefSeq	NT_010966 [ SRS ]    NT_010966 [ ENTREZ ]
RefSeq	NW_001838467 [ SRS ]    NW_001838467 [ ENTREZ ]
RefSeq	NW_927095 [ SRS ]    NW_927095 [ ENTREZ ]
AceView	RBBP8 AceView - NCBI
Unigene	Hs.546282 [ SRS ]    Hs.546282 [ NCBI ]     HS546282 [ spliceNest ]
Fast-db	2163 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q8NHQ3 [ SRS]    Q8NHQ3 [ EXPASY ]     Q8NHQ3 [ INTERPRO ]     Q8NHQ3 [ UNIPROT ]
CluSTr	Q8NHQ3
Blocks	Q8NHQ3
HPRD	04990
	Protein Interaction databases
DIP	Q8NHQ3
IntAct	Q8NHQ3
	Polymorphism : SNP, mutations, diseases
OMIM	604124    [ map ]
GENECLINICS	604124
SNP	RBBP8 [dbSNP-NCBI]
SNP	NM_002894 [SNP-NCI]
SNP	NM_203291 [SNP-NCI]
SNP	NM_203292 [SNP-NCI]
SNP	RBBP8 [GeneSNPs - Utah]  RBBP8] [HGBASE - SRS]
HAPMAP	RBBP8 [HAPMAP]
COSMIC	RBBP8 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	RBBP8
	General knowledge
Family Browser	RBBP8 [UCSC Family Browser]
SOURCE	NM_002894
SOURCE	NM_203291
SOURCE	NM_203292
SMD	Hs.546282
SAGE	Hs.546282
GO	cell cycle checkpoint [Amigo]  cell cycle checkpoint
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	DNA repair [Amigo]  DNA repair
GO	regulation of transcription from RNA polymerase II promoter [Amigo]  regulation of transcription from RNA polymerase II promoter
BIOCARTA	ATM Signaling Pathway    [Genes]
PubGene	RBBP8
TreeFam	RBBP8
CTD	5932 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	RBBP8 Related clones (RZPD - Berlin)
	PubMed
PubMed	36 Pubmed reference(s) in LocusLink

Bibliography

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

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

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

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

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

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

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

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	05-2008	Govindaswamy 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

Citation

This paper should be referenced as such :

Chinnadurai G, Subramanian T, Vijayalingam S . RBBP8 (retinoblastoma binding protein 8). Atlas Genet Cytogenet Oncol Haematol. May 2008 . URL : http://AtlasGeneticsOncology.org/Genes/RBBP8ID42066ch18q11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:17:00 2008