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Gene Review

TERF1  -  telomeric repeat binding factor (NIMA...

Homo sapiens

Synonyms: NIMA-interacting protein 2, PIN2, TRBF1, TRF, TRF1, ...
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Disease relevance of TERF1


Psychiatry related information on TERF1

  • The constellation of normal quantitative but abnormal kinetic LRF and TRF responses supports the hypothesis that the endocrine changes seen in anorexia nervosa are consistent with hypothalamic dysfunction [5].
  • For the assessment of behaviour problems the Child Behavior Checklist (CBCL), Teacher Self Report (TRF), and Youth Self Report (YSR) were filled out by parents, teachers, and children, respectively [6].
  • Children were screened for ADHD and other problems, using the C-DISC, CBLC, TRF and the Social Adjustment Inventory [7].

High impact information on TERF1


Chemical compound and disease context of TERF1


Biological context of TERF1


Anatomical context of TERF1

  • Control experiments disclosed a novel testis-specific splice variant of TERF1 in human testes [16].
  • Analysis of rodent spermatocytes reveals Trf1 at mouse, TRF2 at rat, and mammalian Rap1 at meiotic telomeres of both rodents [20].
  • Interestingly, Pin2/TRF1 specifically localizes to mitotic spindles in mitotic cells and affects the microtubule polymerization in vitro [21].
  • Expression of TRF1 and TRF2 mRNAs was greater in the normal cells than in human malignant hematopoietic cell lines and in 16 samples of patients with acute leukemia [22].
  • Of 20 gastric carcinomas examined, 10 (50%) and 12 (60%) expressed TRF1 and TRF2 at higher levels than did non-neoplastic mucosa, respectively [23].

Associations of TERF1 with chemical compounds


Physical interactions of TERF1

  • Fbx4 interacts with both Pin2 and TRF1 isoforms and promotes their ubiquitination in vitro and in vivo [28].
  • Pin2/TRF1 bound EB1 both in vitro and in vivo and they also co-localize at the mitotic spindle in cells [21].
  • Furthermore, POT1 binding was regulated by the TRF1 complex in response to telomere length [29].
  • Although each of the five ankyrin repeat clusters independently binds to TRF1, only three of the five bind toTAB182 [30].
  • SALL1 has recently been shown to localize to chromocenters and other heterochromatin foci in murine fibroblasts and to interact with the telomere-repeat-binding factor TRF1/PIN2 [31].

Enzymatic interactions of TERF1

  • Furthermore, activated ATM directly phosphorylated Pin2/TRF1 preferentially on the conserved Ser(219)-Gln site in vitro and in vivo [32].

Regulatory relationships of TERF1


Other interactions of TERF1


Analytical, diagnostic and therapeutic context of TERF1


  1. Expression of mRNAs for telomeric repeat binding factor (TRF)-1 and TRF2 in atypical adenomatous hyperplasia and adenocarcinoma of the lung. Nakanishi, K., Kawai, T., Kumaki, F., Hiroi, S., Mukai, M., Ikeda, E., Koering, C.E., Gilson, E. Clin. Cancer Res. (2003) [Pubmed]
  2. Genetic variation in telomeric repeat binding factors 1 and 2 in aplastic anemia. Savage, S.A., Calado, R.T., Xin, Z.T., Ly, H., Young, N.S., Chanock, S.J. Exp. Hematol. (2006) [Pubmed]
  3. 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]
  4. Telomerase reverse transcriptase and telomeric-repeat binding factor protein 1 as regulators of telomerase activity in pancreatic cancer cells. Yajima, T., Yagihashi, A., Kameshima, H., Kobayashi, D., Hirata, K., Watanabe, N. Br. J. Cancer (2001) [Pubmed]
  5. Delayed pituitary hormone response to LRF and TRF in patients with anorexia nervosa and with secondary amenorrhea associated with simple weight loss. Vigersky, R.A., Loriaux, D.L., Andersen, A.E., Mecklenburg, R.S., Vaitukaitis, J.L. J. Clin. Endocrinol. Metab. (1976) [Pubmed]
  6. Behaviour problems in children with dyslexia. Heiervang, E., Stevenson, J., Lund, A., Hugdahl, K. Nordic journal of psychiatry. (2001) [Pubmed]
  7. The psychosocial functioning of children and spouses of adults with ADHD. Minde, K., Eakin, L., Hechtman, L., Ochs, E., Bouffard, R., Greenfield, B., Looper, K. Journal of child psychology and psychiatry, and allied disciplines. (2003) [Pubmed]
  8. TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex. Ye, J.Z., de Lange, T. Nat. Genet. (2004) [Pubmed]
  9. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Zhu, X.D., Küster, B., Mann, M., Petrini, J.H., de Lange, T. Nat. Genet. (2000) [Pubmed]
  10. TIN2, a new regulator of telomere length in human cells. Kim, S.H., Kaminker, P., Campisi, J. Nat. Genet. (1999) [Pubmed]
  11. Up-regulation of telomere-binding TRF1, TRF2 related to reactive oxygen species induced by As(2)O(3) in MGC-803 cells. Zhang, Y., Cao, E.H., Qin, J.F. Eur. J. Pharmacol. (2005) [Pubmed]
  12. Tomato TERF1 modulates ethylene response and enhances osmotic stress tolerance by activating expression of downstream genes. Huang, Z., Zhang, Z., Zhang, X., Zhang, H., Huang, D., Huang, R. FEBS Lett. (2004) [Pubmed]
  13. Combined hypothalamic hypothyroidism and secondary adrenal insufficiency. Misdiagnosed as primary hypothyroidism. Farese, R.V., Rodriguez, M.E., O'Malley, B.C., Jamieson, E., Pollet, R.J. Arch. Intern. Med. (1979) [Pubmed]
  14. Plasma ACTH and cortisol responses to TRF, vasopressin or hypoglycemia in cushing's disease and nelson's syndrome. Krieger, D.T., Luria, M. J. Clin. Endocrinol. Metab. (1977) [Pubmed]
  15. Urinary excretion of transferrin by non-insulin-dependent diabetics: a marker for early complications? Cheung, C.K., Cockram, C.S., Yeung, V.T., Swaminathan, R. Clin. Chem. (1989) [Pubmed]
  16. Characterization of the telomere complex, TERF1 and TERF2 genes in muntjac species with fusion karyotypes. Hartmann, N., Scherthan, H. Exp. Cell Res. (2005) [Pubmed]
  17. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Broccoli, D., Smogorzewska, A., Chong, L., de Lange, T. Nat. Genet. (1997) [Pubmed]
  18. The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Zhou, X.Z., Lu, K.P. Cell (2001) [Pubmed]
  19. Control of human telomere length by TRF1 and TRF2. Smogorzewska, A., van Steensel, B., Bianchi, A., Oelmann, S., Schaefer, M.R., Schnapp, G., de Lange, T. Mol. Cell. Biol. (2000) [Pubmed]
  20. Mammalian meiotic telomeres: protein composition and redistribution in relation to nuclear pores. Scherthan, H., Jerratsch, M., Li, B., Smith, S., Hultén, M., Lock, T., de Lange, T. Mol. Biol. Cell (2000) [Pubmed]
  21. Involvement of the telomeric protein Pin2/TRF1 in the regulation of the mitotic spindle. Nakamura, M., Zhou, X.Z., Kishi, S., Lu, K.P. FEBS Lett. (2002) [Pubmed]
  22. Role of human telomerase reverse transcriptase and telomeric-repeat binding factor proteins 1 and 2 in human hematopoietic cells. Yamada, K., Yajima, T., Yagihashi, A., Kobayashi, D., Koyanagi, Y., Asanuma, K., Yamada, M., Moriai, R., Kameshima, H., Watanabe, N. Jpn. J. Cancer Res. (2000) [Pubmed]
  23. 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]
  24. A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle. Nakamura, M., Zhou, X.Z., Kishi, S., Kosugi, I., Tsutsui, Y., Lu, K.P. Curr. Biol. (2001) [Pubmed]
  25. Comparison between TRF2 and TRF1 of their telomeric DNA-bound structures and DNA-binding activities. Hanaoka, S., Nagadoi, A., Nishimura, Y. Protein Sci. (2005) [Pubmed]
  26. Association of nucleoside diphosphate kinase nm23-H2 with human telomeres. Nosaka, K., Kawahara, M., Masuda, M., Satomi, Y., Nishino, H. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  27. Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. Kim, M.K., Kang, M.R., Nam, H.W., Bae, Y.S., Kim, Y.S., Chung, I.K. J. Biol. Chem. (2008) [Pubmed]
  28. The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance. Lee, T.H., Perrem, K., Harper, J.W., Lu, K.P., Zhou, X.Z. J. Biol. Chem. (2006) [Pubmed]
  29. POT1 as a terminal transducer of TRF1 telomere length control. Loayza, D., De Lange, T. Nature (2003) [Pubmed]
  30. The telomeric poly(ADP-ribose) polymerase, tankyrase 1, contains multiple binding sites for telomeric repeat binding factor 1 (TRF1) and a novel acceptor, 182-kDa tankyrase-binding protein (TAB182). Seimiya, H., Smith, S. J. Biol. Chem. (2002) [Pubmed]
  31. Interaction of the developmental regulator SALL1 with UBE2I and SUMO-1. Netzer, C., Bohlander, S.K., Rieger, L., Müller, S., Kohlhase, J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  32. Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks. Kishi, S., Zhou, X.Z., Ziv, Y., Khoo, C., Hill, D.E., Shiloh, Y., Lu, K.P. J. Biol. Chem. (2001) [Pubmed]
  33. Telomere length homeostasis requires that telomerase levels are limiting. Cristofari, G., Lingner, J. EMBO J. (2006) [Pubmed]
  34. Protection of internal (TTAGGG)n repeats in Chinese hamster cells by telomeric protein TRF1. Krutilina, R.I., Smirnova, A.N., Mudrak, O.S., Pleskach, N.M., Svetlova, M.P., Oei, S.L., Yau, P.M., Bradbury, E.M., Zalensky, A.O., Tomilin, N.V. Oncogene (2003) [Pubmed]
  35. Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner. Sbodio, J.I., Chi, N.W. J. Biol. Chem. (2002) [Pubmed]
  36. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Cook, B.D., Dynek, J.N., Chang, W., Shostak, G., Smith, S. Mol. Cell. Biol. (2002) [Pubmed]
  37. Plk1 phosphorylation of TRF1 is essential for its binding to telomeres. Wu, Z.Q., Yang, X., Weber, G., Liu, X. J. Biol. Chem. (2008) [Pubmed]
  38. Study on the expression and mutation of human telomeric repeat binding factor (hTRF1) in 10 malignant hematopoietic cell lines. Sun, J., Huang, H., Zhu, Y.Y., Lan, J.P., Li, J.Y., Lai, X.Y., Yu, J. Journal of Zhejiang University. Science. B. (2005) [Pubmed]
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