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| | 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). |
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| 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). |
| Molecular cloning and characterization of a novel retinoblastoma-binding protein. |
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| PMID 9721205 |
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| 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. |
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| PMID 9535825 |
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| Characterization of a carboxy-terminal BRCA1 interacting protein. |
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| Oncogene. 1998 Nov 5;17(18):2279-85. |
| PMID 9811458 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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