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Gene Review

CTBP2  -  C-terminal binding protein 2

Homo sapiens

Synonyms: C-terminal-binding protein 2, CtBP2, ribeye
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High impact information on CTBP2

  • Our results suggest a model in which the nuclear localization of CtBP proteins is influenced by the CtBP2 NLS, by binding to PXDLS motif partner proteins, and through the effect of NADH on CtBP dimerization [1].
  • ZNF217 has been purified in complexes that contain repressor proteins such as CtBP2, suggesting that it acts as a transcriptional repressor [2].
  • Substitution of the N-terminal domain of CtBP1 with the corresponding CtBP2 domain confers a dominant nuclear localization pattern to CtBP1 [3].
  • Furthermore, lack of acetylation at Lys-10 renders CtBP2 to be more efficient in repression of the E-cadherin promoter [3].
  • Our studies have revealed the important roles of acetylation in regulating subcellular localization and transcriptional activity of CtBP2 [3].

Biological context of CTBP2

  • CtBP2 with a single amino acid substitution at Lys-10 (K10R) is predominantly localized in the cytoplasm [3].
  • Furthermore, point mutation of two CtBP2 residues forming part of the structure of the recognition cleft for a PxDLS motif also ablates the interaction with a GxDLS motif [4].
  • A transcriptional activation function encoded by the E1A N-terminal region was efficiently inhibited by CtBP2 but not by a mutant with an N-terminal deletion or by a mutant deficient in interaction with E1A [5].
  • Expression of avian C-terminal binding proteins (Ctbp1 and Ctbp2) during embryonic development [6].
  • Furthermore, mutational analysis of SOX6 showed that binding to CtBP2, and its responsiveness to this co-repressor, were dependent on a short amino acid sequence motif PLNLSS [7].

Anatomical context of CTBP2

  • For instance, Ctbp1 is predominantly expressed in the epiblast, whereas Ctbp2 is in the primitive streak at HH stage 3 [6].
  • Similarly, although both genes display similar expression patterns in early somitogenesis, in mature somites, Ctbp1 transcripts are located in myotomal cells, whereas Ctbp2 transcripts are observed in dermomyotomal cells [6].
  • Finally, we found that emigrating neural crest cells express Ctbp2, whereas dorsal root ganglia express Ctbp1 [6].
  • RESULTS: Here we show that amino acids (a.a.) 4-14 of CtBP2 direct CtBP2 into an almost exclusively nuclear distribution in cell lines of diverse origins [8].
  • A binding site for the corepressor CtBP2 was also grafted onto the domain, creating a new PHD domain that can specifically bind CtBP2 both in vitro and in the context of a eukaryotic cell nucleus [9].

Associations of CTBP2 with chemical compounds


Physical interactions of CTBP2

  • We present evidence that CtBP2 also interacts with FHL3 and demonstrate that the three proteins co-elute in gel filtration experiments [11].
  • Additionally, E1A also displaced the histone methyltransferase G9a and the E-box repressor ZEB from the CtBP2 complex through the C-terminal CtBP-binding domain [5].

Other interactions of CTBP2

  • Different but closely linked regions of BKLF mediate contact with CtBP2 and FHL3 [11].
  • There are two highly homologous genes, CtBP1 and CtBP2 that encode CtBP [12].
  • Here, we show that HIC1 interacts with both CtBP1 and CtBP2 and that this interaction is stimulated by agents increasing NADH levels [4].
  • Here we show that Hdm2 can also repress p53 activity through the recruitment of a known transcriptional corepressor, hCtBP2 [13].
  • These results show that SOX6 can recruit CtBP2 to repress transcription from the Fgf-3 promoter [7].

Analytical, diagnostic and therapeutic context of CTBP2

  • We have cloned the avian orthologues of Ctbp1 and Ctbp2 and examined their expression pattern by whole-mount in situ hybridization between Hamburger and Hamilton (HH) stages 3 and 24 [6].


  1. Mechanisms directing the nuclear localization of the CtBP family proteins. Verger, A., Quinlan, K.G., Crofts, L.A., Spanò, S., Corda, D., Kable, E.P., Braet, F., Crossley, M. Mol. Cell. Biol. (2006) [Pubmed]
  2. Identification of Genes Directly Regulated by the Oncogene ZNF217 Using Chromatin Immunoprecipitation (ChIP)-Chip Assays. Krig, S.R., Jin, V.X., Bieda, M.C., O'geen, H., Yaswen, P., Green, R., Farnham, P.J. J. Biol. Chem. (2007) [Pubmed]
  3. Acetylation by p300 regulates nuclear localization and function of the transcriptional corepressor CtBP2. Zhao, L.J., Subramanian, T., Zhou, Y., Chinnadurai, G. J. Biol. Chem. (2006) [Pubmed]
  4. A L225A substitution in the human tumour suppressor HIC1 abolishes its interaction with the corepressor CtBP. Stankovic-Valentin, N., Verger, A., Deltour-Balerdi, S., Quinlan, K.G., Crossley, M., Leprince, D. FEBS J. (2006) [Pubmed]
  5. Changes in C-terminal Binding Protein 2 (CtBP2) Corepressor Complex Induced by E1A and Modulation of E1A Transcriptional Activity by CtBP2. Zhao, L.J., Subramanian, T., Chinnadurai, G. J. Biol. Chem. (2006) [Pubmed]
  6. Expression of avian C-terminal binding proteins (Ctbp1 and Ctbp2) during embryonic development. Van Hateren, N., Shenton, T., Borycki, A.G. Dev. Dyn. (2006) [Pubmed]
  7. SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter. Murakami, A., Ishida, S., Thurlow, J., Revest, J.M., Dickson, C. Nucleic Acids Res. (2001) [Pubmed]
  8. Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins. Bergman, L.M., Morris, L., Darley, M., Mirnezami, A.H., Gunatilake, S.C., Blaydes, J.P. BMC Cell Biol. (2006) [Pubmed]
  9. Engineering a protein scaffold from a PHD finger. Kwan, A.H., Gell, D.A., Verger, A., Crossley, M., Matthews, J.M., Mackay, J.P. Structure (Camb.) (2003) [Pubmed]
  10. Synaptic connectivity in the midget-parvocellular pathway of primate central retina. Jusuf, P.R., Martin, P.R., Grünert, U. J. Comp. Neurol. (2006) [Pubmed]
  11. The LIM protein FHL3 binds basic Krüppel-like factor/Krüppel-like factor 3 and its co-repressor C-terminal-binding protein 2. Turner, J., Nicholas, H., Bishop, D., Matthews, J.M., Crossley, M. J. Biol. Chem. (2003) [Pubmed]
  12. The transcriptional co-repressor C-terminal binding protein (CtBP) associates with centrosomes during mitosis. Spyer, M., Allday, M.J. Cell Cycle (2006) [Pubmed]
  13. Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription. Mirnezami, A.H., Campbell, S.J., Darley, M., Primrose, J.N., Johnson, P.W., Blaydes, J.P. Curr. Biol. (2003) [Pubmed]
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