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Gene Review

SET  -  SET nuclear proto-oncogene

Homo sapiens

Synonyms: 2PP2A, HLA-DR-associated protein II, I-2PP2A, I2PP2A, IGAAD, ...
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Disease relevance of SET


Psychiatry related information on SET

  • The high physical activity required by the mountainous land of Tafi del Valle may be the cause of increased BMD at the proximal femur among these people [5].

High impact information on SET


Chemical compound and disease context of SET


Biological context of SET


Anatomical context of SET

  • Recently, we have purified TAF-I as 39- and 41-kDa polypeptides from HeLa cells [3].
  • Immunofluorescence analyses showed that SET/TAF-Ibeta and CAN/Nup214 are found in the nucleus and the nuclear envelope, respectively, whereas the majority of SET/TAF-Ibeta-CAN/Nup214 is localized in the nucleus [17].
  • Here we report on two putative HLA class II associated proteins (PHAPI and PHAPII) which have been purified from the cytosolic fraction of the human lymphoblastoid B-cell line H2LCL using an affinity matrix composed of the synthetic biotinylated cytoplasmic region of the DR2 alpha chain immobilized on avidin agarose [18].
  • In this in vitro study, the potential of rFVIIa to down-regulate fibrinolysis via activation of TAFI was investigated. rFVIIa was able to prolong clot lysis time in plasmas from 17 patients with severe hemophilia A [19].
  • We detected the beta form of TAF-I in Xenopus oocytes and eggs by immunoblotting, and the cloning of its cDNA led us to conclude that Xenopus TAF-Ibeta also decondenses sperm chromatin [20].

Associations of SET with chemical compounds

  • Inhibition of either TAFI activation or Factor XIa exhibited equivalent profibrinolytic effects [6].
  • Reviparin administered twice daily plus vitamin K antagonist is more effective in inhibiting in vivo thrombin generation compared to intravenous unfractionated heparin plus vitamin K antagonist, and reviparin once daily produced significantly higher TFPI release and greater reduction in TAFI and fibrinogen levels [21].
  • The factor stimulating Ad core DNA replication, designated as template activating factor I (TAF-I), was purified by successive steps of ammonium sulfate precipitation, column chromatographies on phosphocellulose and Q-Sepharose, and glycerol density gradient centrifugation [22].
  • We have identified a novel coregulatory protein, template-activating factor-Ibeta (TAF-Ibeta), which binds to ERalpha in vitro when the receptor is not complexed with an estrogen response element [9].
  • The level of the TAF-I proteins does not change significantly during the cell cycle progression in either HeLa cells synchronized with an excess concentration of thymidine or NIH 3T3 cells released from the serum-depleted state [23].

Physical interactions of SET


Regulatory relationships of SET


Other interactions of SET

  • Several polypeptides were identified by mass spectrometry, among which was ANP32B, a member of the acidic nuclear protein 32 family which takes part in the formation of the template-activating factor I/Set oncoprotein (TAF-I/Set) complex [15].
  • I1PP2A and I2PP2A. Two potent protein phosphatase 2A-specific inhibitor proteins [27].
  • Finally, Set/TAF-Ibeta and pp32 associate with an endogenous estrogen receptor-regulated gene, EB1, in the hypoacetylated transcriptionally inactive state but not with the hyperacetylated transcriptionally active form [28].
  • Similarly, stably transfected THAP7 associates with endogenous TAF-Ibeta in intact cells [29].
  • These results suggest that TAF-Ibeta plays an important role in MLL-mediated transcription and possibly chromatin maintenance [25].

Analytical, diagnostic and therapeutic context of SET


  1. Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Fan, Z., Beresford, P.J., Oh, D.Y., Zhang, D., Lieberman, J. Cell (2003) [Pubmed]
  2. The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A. Li, M., Makkinje, A., Damuni, Z. J. Biol. Chem. (1996) [Pubmed]
  3. Replication factor encoded by a putative oncogene, set, associated with myeloid leukemogenesis. Nagata, K., Kawase, H., Handa, H., Yano, K., Yamasaki, M., Ishimi, Y., Okuda, A., Kikuchi, A., Matsumoto, K. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. PCOTH, a novel gene overexpressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-Ibeta/SET. Anazawa, Y., Nakagawa, H., Furihara, M., Ashida, S., Tamura, K., Yoshioka, H., Shuin, T., Fujioka, T., Katagiri, T., Nakamura, Y. Cancer Res. (2005) [Pubmed]
  5. Bone mineral density in a native population of Argentina with low calcium intake. Spindler, A., Lucero, E., Berman, A., Paz, S., Vega, E., Mautalen, C. J. Rheumatol. (1995) [Pubmed]
  6. Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis. Von dem Borne, P.A., Bajzar, L., Meijers, J.C., Nesheim, M.E., Bouma, B.N. J. Clin. Invest. (1997) [Pubmed]
  7. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Lisman, T., Leebeek, F.W., Mosnier, L.O., Bouma, B.N., Meijers, J.C., Janssen, H.L., Nieuwenhuis, H.K., De Groot, P.G. Gastroenterology (2001) [Pubmed]
  8. Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET. Ten Klooster, J.P., Leeuwen, I.V., Scheres, N., Anthony, E.C., Hordijk, P.L. EMBO J. (2007) [Pubmed]
  9. A novel estrogen receptor alpha-associated protein, template-activating factor Ibeta, inhibits acetylation and transactivation. Loven, M.A., Muster, N., Yates, J.R., Nardulli, A.M. Mol. Endocrinol. (2003) [Pubmed]
  10. Insulin resistance is associated with increased circulating level of thrombin-activatable fibrinolysis inhibitor in type 2 diabetic patients. Hori, Y., Gabazza, E.C., Yano, Y., Katsuki, A., Suzuki, K., Adachi, Y., Sumida, Y. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  11. Thrombin activatable fibrinolysis inhibitor (TAFI) levels in patients with coronary artery disease investigated by angiography. Schroeder, V., Chatterjee, T., Mehta, H., Windecker, S., Pham, T., Devantay, N., Meier, B., Kohler, H.P. Thromb. Haemost. (2002) [Pubmed]
  12. Elevated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Overt and Subclinical Hypothyroid Patients Were Reduced by Levothyroxine Replacement. Akinci, B., Comlekci, A., Ali Ozcan, M., Demir, T., Yener, S., Demirkan, F., Yuksel, F., Yesil, S. Endocr. J. (2007) [Pubmed]
  13. Simvastatin treatment improves endothelial function and increases fibrinolysis in patients with hypercholestrolemia. Guven, G.S., Atalar, E., Yavuz, B., Beyazit, Y., Kekilli, M., Kilicarslan, A., Sahiner, L., Oz, G., Ozer, N., Aksoyek, S., Haznedaroglu, I.C., Sozen, T. Journal of the National Medical Association. (2006) [Pubmed]
  14. The oncoprotein Set/TAF-1beta, an inhibitor of histone acetyltransferase, inhibits active demethylation of DNA, integrating DNA methylation and transcriptional silencing. Cervoni, N., Detich, N., Seo, S.B., Chakravarti, D., Szyf, M. J. Biol. Chem. (2002) [Pubmed]
  15. Regulation of adeno-associated virus DNA replication by the cellular TAF-I/set complex. Pegoraro, G., Marcello, A., Myers, M.P., Giacca, M. J. Virol. (2006) [Pubmed]
  16. The histone chaperone SET/TAF-Ibeta interacts functionally with the CREB-binding protein. Karetsou, Z., Martic, G., Sflomos, G., Papamarcaki, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  17. Aberrant intracellular localization of SET-CAN fusion protein, associated with a leukemia, disorganizes nuclear export. Saito, S., Miyaji-Yamaguchi, M., Nagata, K. Int. J. Cancer (2004) [Pubmed]
  18. Purification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII. Vaesen, M., Barnikol-Watanabe, S., Götz, H., Awni, L.A., Cole, T., Zimmermann, B., Kratzin, H.D., Hilschmann, N. Biol. Chem. Hoppe-Seyler (1994) [Pubmed]
  19. Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A. Lisman, T., Mosnier, L.O., Lambert, T., Mauser-Bunschoten, E.P., Meijers, J.C., Nieuwenhuis, H.K., de Groot, P.G. Blood (2002) [Pubmed]
  20. Sperm chromatin decondensation by template activating factor I through direct interaction with basic proteins. Matsumoto, K., Nagata, K., Miyaji-Yamaguchi, M., Kikuchi, A., Tsujimoto, M. Mol. Cell. Biol. (1999) [Pubmed]
  21. Randomized trial of different regimens of heparins and in vivo thrombin generation in acute deep vein thrombosis. Kakkar, V.V., Hoppenstead, D.A., Fareed, J., Kadziola, Z., Scully, M., Nakov, R., Breddin, H.K. Blood (2002) [Pubmed]
  22. Template activating factor I, a novel host factor required to stimulate the adenovirus core DNA replication. Matsumoto, K., Nagata, K., Ui, M., Hanaoka, F. J. Biol. Chem. (1993) [Pubmed]
  23. Cellular localization and expression of template-activating factor I in different cell types. Nagata, K., Saito, S., Okuwaki, M., Kawase, H., Furuya, A., Kusano, A., Hanai, N., Okuda, A., Kikuchi, A. Exp. Cell Res. (1998) [Pubmed]
  24. Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I. Suzuki, T., Muto, S., Miyamoto, S., Aizawa, K., Horikoshi, M., Nagai, R. J. Biol. Chem. (2003) [Pubmed]
  25. Synergistic action of MLL, a TRX protein with template activating factor-I, a histone chaperone. Shimoyama, T., Kato, K., Miyaji-Yamaguchi, M., Nagata, K. FEBS Lett. (2005) [Pubmed]
  26. The oncoprotein I-2PP2A/SET negatively regulates the MEK/ERK pathway and cell proliferation. Fukukawa, C., Shima, H., Tanuma, N., Okada, T., Kato, N., Adachi, Y., Kikuchi, K. Int. J. Oncol. (2005) [Pubmed]
  27. I1PP2A and I2PP2A. Two potent protein phosphatase 2A-specific inhibitor proteins. Li, M., Damuni, Z. Methods Mol. Biol. (1998) [Pubmed]
  28. A signaling role of histone-binding proteins and INHAT subunits pp32 and Set/TAF-Ibeta in integrating chromatin hypoacetylation and transcriptional repression. Kutney, S.N., Hong, R., Macfarlan, T., Chakravarti, D. J. Biol. Chem. (2004) [Pubmed]
  29. Thanatos-associated protein 7 associates with template activating factor-Ibeta and inhibits histone acetylation to repress transcription. Macfarlan, T., Parker, J.B., Nagata, K., Chakravarti, D. Mol. Endocrinol. (2006) [Pubmed]
  30. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis. van Tilburg, N.H., Rosendaal, F.R., Bertina, R.M. Blood (2000) [Pubmed]
  31. Roles of thermal instability and proteolytic cleavage in regulation of activated thrombin-activable fibrinolysis inhibitor. Boffa, M.B., Bell, R., Stevens, W.K., Nesheim, M.E. J. Biol. Chem. (2000) [Pubmed]
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