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Gene Review

TINF2  -  TERF1 (TRF1)-interacting nuclear factor 2

Homo sapiens

Synonyms: DKCA3, TERF1-interacting nuclear factor 2, TIN2, TRF1-interacting nuclear protein 2
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Disease relevance of TINF2


High impact information on TINF2


Biological context of TINF2

  • Chromosome telomeres of humans and many model organisms contain a structure called a t-loop, which is maintained by TERF, TINF2, Pot1, and other proteins [6].
  • Consistent with the finding that a wide variety of human tissues expresses low endogenous levels of TINF2, its proximal promoter region has the typical features of a housekeeping gene [7].
  • They are interconnected by three additional shelterin proteins, TIN2, TPP1, and Rap1, forming a complex that allows cells to distinguish telomeres from sites of DNA damage [8].
  • Using human mammary epithelial cells in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains [9].

Anatomical context of TINF2


Physical interactions of TINF2


Regulatory relationships of TINF2

  • Consistent with this model, overexpression of TPP1 enhanced TIN2-TRF2 association [13].

Other interactions of TINF2

  • Up-regulation of telomere-binding proteins, TRF1, TRF2, and TIN2 is related to telomere shortening during human multistep hepatocarcinogenesis [14].
  • The results suggest that gastric carcinomas with short telomeres need high levels of telomerase activity and large quantity of TRFs and TIN2, whereas those with long telomeres do not require high levels of telomerase activity and telomere associated proteins [1].
  • The TIN2 domains were sensitive to DNase, but not RNase, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein 1gamma [9].


  1. Expression of telomeric repeat binding factor 1 and 2 and TRF1-interacting nuclear protein 2 in human gastric carcinomas. Matsutani, N., Yokozaki, H., Tahara, E., Tahara, H., Kuniyasu, H., Haruma, K., Chayama, K., Yasui, W., Tahara, E. Int. J. Oncol. (2001) [Pubmed]
  2. Down-regulation of TRF1, TRF2 and TIN2 genes is important to maintain telomeric DNA for gastric cancers. Yamada, M., Tsuji, N., Nakamura, M., Moriai, R., Kobayashi, D., Yagihashi, A., Watanabe, N. Anticancer Res. (2002) [Pubmed]
  3. Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in patients with adult T-cell leukemia. Bellon, M., Datta, A., Brown, M., Pouliquen, J.F., Couppie, P., Kazanji, M., Nicot, C. Int. J. Cancer (2006) [Pubmed]
  4. TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex. Ye, J.Z., de Lange, T. Nat. Genet. (2004) [Pubmed]
  5. TIN2, a new regulator of telomere length in human cells. Kim, S.H., Kaminker, P., Campisi, J. Nat. Genet. (1999) [Pubmed]
  6. Polypeptide components of telomere nucleoprotein complex. Kuimov, A.N. Biochemistry Mosc. (2004) [Pubmed]
  7. The human TINF2 gene organisation and chromosomal localization. Simonsson, T. Biochimie (2001) [Pubmed]
  8. Shelterin: the protein complex that shapes and safeguards human telomeres. de Lange, T. Genes Dev. (2005) [Pubmed]
  9. Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2. Kaminker, P., Plachot, C., Kim, S.H., Chung, P., Crippen, D., Petersen, O.W., Bissell, M.J., Campisi, J., Lelièvre, S.A. J. Cell. Sci. (2005) [Pubmed]
  10. Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells. Yamada, K., Yagihashi, A., Yamada, M., Asanuma, K., Moriai, R., Kobayashi, D., Tsuji, N., Watanabe, N. Anticancer Res. (2002) [Pubmed]
  11. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. Ye, J.Z., Donigian, J.R., van Overbeek, M., Loayza, D., Luo, Y., Krutchinsky, A.N., Chait, B.T., de Lange, T. J. Biol. Chem. (2004) [Pubmed]
  12. TIN2 mediates functions of TRF2 at human telomeres. Kim, S.H., Beausejour, C., Davalos, A.R., Kaminker, P., Heo, S.J., Campisi, J. J. Biol. Chem. (2004) [Pubmed]
  13. A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. O'Connor, M.S., Safari, A., Xin, H., Liu, D., Songyang, Z. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  14. Up-regulation of telomere-binding proteins, TRF1, TRF2, and TIN2 is related to telomere shortening during human multistep hepatocarcinogenesis. Oh, B.K., Kim, Y.J., Park, C., Park, Y.N. Am. J. Pathol. (2005) [Pubmed]
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