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Gene Review

SREBF2  -  sterol regulatory element binding...

Homo sapiens

Synonyms: BHLHD2, Class D basic helix-loop-helix protein 2, SREBP-2, SREBP2, Sterol regulatory element-binding protein 2, ...
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Disease relevance of SREBF2


Psychiatry related information on SREBF2


High impact information on SREBF2


Chemical compound and disease context of SREBF2


Biological context of SREBF2


Anatomical context of SREBF2


Associations of SREBF2 with chemical compounds


Physical interactions of SREBF2

  • Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity [21].
  • Truncation of SREBP-2 at its COOH terminus prevents the formation of complexes with SCAP and simultaneously reduces proteolytic cleavage [22].
  • The results suggest that an increased cellular cholesterol load causes accumulation of SREBP-2 in the smooth endoplasmic reticulum and, therefore, that membrane cholesterol ester may be one signal allowing exit of the SREBP-2/SREBP-cleavage-regulating protein complex to the Golgi [23].

Regulatory relationships of SREBF2


Other interactions of SREBF2


Analytical, diagnostic and therapeutic context of SREBF2

  • SREBP-1 68-kDa protein levels were maintained throughout progression, however, SREBP-2 68-kDa protein expression increased after castration and during progression (3-fold) [28].
  • The in vitro pull-down and in vivo co-immunoprecipitation experiments showed the direct interaction between SREBP-2 and HNF-4 [13].
  • Gel mobility shift assays showed that recombinant SREBP-2-NT protein (1-468) binds to a double-stranded LRP1 DNA fragment (215 to 245) containing a wild-type (wt) SRE sequence but not to a mutated SRE (mt) sequence (5-GAATTCGA-3') [29].
  • Chromatin immunoprecipitation assay demonstrated that serum starvation enhanced the association of SREBP2 and the ABCA1 promoter in ECs [27].
  • In untreated animals the soluble fragment of SREBP-1, but not of SREBP-2, was detected by immunoblotting of a liver nuclear extract [30].


  1. Human prostate cancer cells lack feedback regulation of low-density lipoprotein receptor and its regulator, SREBP2. Chen, Y., Hughes-Fulford, M. Int. J. Cancer (2001) [Pubmed]
  2. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element-Binding Protein-2 (SREBP-2). Shin, D.J., Osborne, T.F. J. Biol. Chem. (2003) [Pubmed]
  3. Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes. Le Lay, S., Krief, S., Farnier, C., Lefrère, I., Le Liepvre, X., Bazin, R., Ferré, P., Dugail, I. J. Biol. Chem. (2001) [Pubmed]
  4. Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. Yang, Y.A., Morin, P.J., Han, W.F., Chen, T., Bornman, D.M., Gabrielson, E.W., Pizer, E.S. Exp. Cell Res. (2003) [Pubmed]
  5. Analysis of the SREBF2 gene as a genetic risk factor for vascular dementia. Kim, Y., Nam, Y.J., Lee, C. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2005) [Pubmed]
  6. Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Sakai, J., Duncan, E.A., Rawson, R.B., Hua, X., Brown, M.S., Goldstein, J.L. Cell (1996) [Pubmed]
  7. SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein. Oliner, J.D., Andresen, J.M., Hansen, S.K., Zhou, S., Tjian, R. Genes Dev. (1996) [Pubmed]
  8. Sterol-resistant transcription in CHO cells caused by gene rearrangement that truncates SREBP-2. Yang, J., Sato, R., Goldstein, J.L., Brown, M.S. Genes Dev. (1994) [Pubmed]
  9. Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia. Kojima, M., Degawa, M. Journal of applied toxicology : JAT. (2006) [Pubmed]
  10. IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells: evidence that IDH1 may regulate lipogenesis in hepatic cells. Shechter, I., Dai, P., Huo, L., Guan, G. J. Lipid Res. (2003) [Pubmed]
  11. Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Hua, X., Wu, J., Goldstein, J.L., Brown, M.S., Hobbs, H.H. Genomics (1995) [Pubmed]
  12. Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2). Miserez, A.R., Cao, G., Probst, L.C., Hobbs, H.H. Genomics (1997) [Pubmed]
  13. Sterol regulatory element-binding protein-2 interacts with hepatocyte nuclear factor-4 to enhance sterol isomerase gene expression in hepatocytes. Misawa, K., Horiba, T., Arimura, N., Hirano, Y., Inoue, J., Emoto, N., Shimano, H., Shimizu, M., Sato, R. J. Biol. Chem. (2003) [Pubmed]
  14. Spatial distribution and function of sterol regulatory element-binding protein 1a and 2 homo- and heterodimers by in vivo two-photon imaging and spectroscopy fluorescence resonance energy transfer. Zoumi, A., Datta, S., Liaw, L.H., Wu, C.J., Manthripragada, G., Osborne, T.F., Lamorte, V.J. Mol. Cell. Biol. (2005) [Pubmed]
  15. Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade. Kotzka, J., Müller-Wieland, D., Roth, G., Kremer, L., Munck, M., Schürmann, S., Knebel, B., Krone, W. J. Lipid Res. (2000) [Pubmed]
  16. Parallel regulation of sterol regulatory element binding protein-2 and the enzymes of cholesterol and fatty acid synthesis but not ceramide synthesis in cultured human keratinocytes and murine epidermis. Harris, I.R., Farrell, A.M., Holleran, W.M., Jackson, S., Grunfeld, C., Elias, P.M., Feingold, K.R. J. Lipid Res. (1998) [Pubmed]
  17. Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis. Wang, X., Zelenski, N.G., Yang, J., Sakai, J., Brown, M.S., Goldstein, J.L. EMBO J. (1996) [Pubmed]
  18. Caspase-2, a novel lipid sensor under the control of sterol regulatory element binding protein 2. Logette, E., Le Jossic-Corcos, C., Masson, D., Solier, S., Sequeira-Legrand, A., Dugail, I., Lemaire-Ewing, S., Desoche, L., Solary, E., Corcos, L. Mol. Cell. Biol. (2005) [Pubmed]
  19. Insulin-activated Erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding Protein-2 at serine residues 432 and 455 in vivo. Kotzka, J., Lehr, S., Roth, G., Avci, H., Knebel, B., Muller-Wieland, D. J. Biol. Chem. (2004) [Pubmed]
  20. Purification of an interleukin-1 beta converting enzyme-related cysteine protease that cleaves sterol regulatory element-binding proteins between the leucine zipper and transmembrane domains. Wang, X., Pai, J.T., Wiedenfeld, E.A., Medina, J.C., Slaughter, C.A., Goldstein, J.L., Brown, M.S. J. Biol. Chem. (1995) [Pubmed]
  21. Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity. Grimsby, S., Jaensson, H., Dubrovska, A., Lomnytska, M., Hellman, U., Souchelnytskyi, S. FEBS Lett. (2004) [Pubmed]
  22. Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein. Sakai, J., Nohturfft, A., Cheng, D., Ho, Y.K., Brown, M.S., Goldstein, J.L. J. Biol. Chem. (1997) [Pubmed]
  23. A role for smooth endoplasmic reticulum membrane cholesterol ester in determining the intracellular location and regulation of sterol-regulatory-element-binding protein-2. Iddon, C.R., Wilkinson, J., Bennett, A.J., Bennett, J., Salter, A.M., Higgins, J.A. Biochem. J. (2001) [Pubmed]
  24. ATF6 modulates SREBP2-mediated lipogenesis. Zeng, L., Lu, M., Mori, K., Luo, S., Lee, A.S., Zhu, Y., Shyy, J.Y. EMBO J. (2004) [Pubmed]
  25. Transcription factor sterol regulatory element binding protein 2 regulates scavenger receptor Cla-1 gene expression. Tréguier, M., Doucet, C., Moreau, M., Dachet, C., Thillet, J., Chapman, M.J., Huby, T. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  26. Differential effects of sterol regulatory binding proteins 1 and 2 on sterol 12 alpha-hydroxylase. SREBP-2 suppresses the sterol 12 alpha-hydroxylase promoter. del Castillo-Olivares, A., Gil, G. J. Biol. Chem. (2002) [Pubmed]
  27. Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: a novel role of SREBP in regulating cholesterol metabolism. Zeng, L., Liao, H., Liu, Y., Lee, T.S., Zhu, M., Wang, X., Stemerman, M.B., Zhu, Y., Shyy, J.Y. J. Biol. Chem. (2004) [Pubmed]
  28. Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Ettinger, S.L., Sobel, R., Whitmore, T.G., Akbari, M., Bradley, D.R., Gleave, M.E., Nelson, C.C. Cancer Res. (2004) [Pubmed]
  29. Sterol regulatory element-binding protein-2 negatively regulates low density lipoprotein receptor-related protein transcription. Llorente-Cortés, V., Costales, P., Bernués, J., Camino-Lopez, S., Badimon, L. J. Mol. Biol. (2006) [Pubmed]
  30. Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver. Sheng, Z., Otani, H., Brown, M.S., Goldstein, J.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
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