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Gene Review

SCAP  -  SREBF chaperone

Homo sapiens

Synonyms: KIAA0199, PSEC0227, SREBP cleavage-activating protein, Sterol regulatory element-binding protein cleavage-activating protein
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Disease relevance of SCAP


High impact information on SCAP


Biological context of SCAP

  • By contrast, NPC1 proteins carrying a L657F or D787N point mutation, which correspond to the activating SCAP L315F and D443N mutations, respectively, exhibit a gain of function phenotype [9].
  • Here, we use transfection techniques to overexpress a segment of SCAP containing transmembrane helices 1-6 in hamster and human cells [10].
  • Silencing of the mutant SCAP allele accounts for restoration of a normal phenotype in CT60 cells selected for NPC1 expression [11].
  • Downregulation of cholesterol synthesis via the SREBP/SCAP regulatory pathway is common to the initial hydroxycholesterols, but more variations exist with respect to these intermediates functioning as ligands for the nuclear receptor LXRalpha [12].
  • This suggests that SCAP gene expression is under the control of SREBP-1, a key regulator of the expression of genes essential for intracellular lipid metabolism [13].

Anatomical context of SCAP


Associations of SCAP with chemical compounds


Physical interactions of SCAP


Regulatory relationships of SCAP


Other interactions of SCAP

  • These findings suggest that the INSIG-1 protein alters sterol balance by modulating SREBP processing jointly with SCAP [24].
  • Furthermore, our data show that the putative SSD of NPC1 is oriented in the same manner as those of HMG-R and SCAP, providing strong evidence that this domain is functionally important [25].
  • Insig-1 appears to play an essential role in the sterol-mediated trafficking of two proteins with sterol-sensing domains, HMG CoA reductase and SCAP [26].
  • Complex formation occurs when cells express only the COOH-terminal domain of either SREBP-2 or SCAP, indicating that the complex forms between the two COOH-terminal domains [14].
  • Subgroup analysis considering the most frequent (N>/=24) LDL receptor mutations (del191-2, ins313+1-2, C660X, E207K, S285L) revealed further gene-dosage- and gender-dependent effects of the SCAP mutations on LDL-cholesterol concentrations (p=0.0345) [27].

Analytical, diagnostic and therapeutic context of SCAP


  1. SCAP ligands are potent new lipid-lowering drugs. Grand-Perret, T., Bouillot, A., Perrot, A., Commans, S., Walker, M., Issandou, M. Nat. Med. (2001) [Pubmed]
  2. A novel method for viral display of ER membrane proteins on budded baculovirus. Urano, Y., Yamaguchi, M., Fukuda, R., Masuda, K., Takahashi, K., Uchiyama, Y., Iwanari, H., Jiang, S.Y., Naito, M., Kodama, T., Hamakubo, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  3. Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER. Espenshade, P.J., Li, W.P., Yabe, D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. Chloramphenicol sodium succinate kinetics in critically ill patients. Slaughter, R.L., Pieper, J.A., Cerra, B., Brodsky, B., Koup, J.R. Clin. Pharmacol. Ther. (1980) [Pubmed]
  5. Effects of SREBF-1a and SCAP polymorphisms on plasma levels of lipids, severity, progression and regression of coronary atherosclerosis and response to therapy with fluvastatin. Salek, L., Lutucuta, S., Ballantyne, C.M., Gotto Jr, A.M., Marian, A.J. J. Mol. Med. (2002) [Pubmed]
  6. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Yang, T., Espenshade, P.J., Wright, M.E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J.L., Brown, M.S. Cell (2002) [Pubmed]
  7. Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi. DeBose-Boyd, R.A., Brown, M.S., Li, W.P., Nohturfft, A., Goldstein, J.L., Espenshade, P.J. Cell (1999) [Pubmed]
  8. Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Hua, X., Nohturfft, A., Goldstein, J.L., Brown, M.S. Cell (1996) [Pubmed]
  9. The sterol-sensing domain of the Niemann-Pick C1 (NPC1) protein regulates trafficking of low density lipoprotein cholesterol. Millard, E.E., Gale, S.E., Dudley, N., Zhang, J., Schaffer, J.E., Ory, D.S. J. Biol. Chem. (2005) [Pubmed]
  10. Overexpression of membrane domain of SCAP prevents sterols from inhibiting SCAP.SREBP exit from endoplasmic reticulum. Yang, T., Goldstein, J.L., Brown, M.S. J. Biol. Chem. (2000) [Pubmed]
  11. Silencing of the mutant SCAP allele accounts for restoration of a normal phenotype in CT60 cells selected for NPC1 expression. Maguire, J.A., Reagan, J.W. J. Lipid Res. (2005) [Pubmed]
  12. Cholesterol, hydroxycholesterols, and bile acids. Javitt, N.B. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  13. Genomic structure and chromosomal mapping of the human sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) gene. Nakajima, T., Hamakubo, T., Kodama, T., Inazawa, J., Emi, M. J. Hum. Genet. (1999) [Pubmed]
  14. 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]
  15. Sterol regulatory element-binding protein family as global regulators of lipid synthetic genes in energy metabolism. Shimano, H. Vitam. Horm. (2002) [Pubmed]
  16. Vascular endothelial growth factor activation of sterol regulatory element binding protein: a potential role in angiogenesis. Zhou, R.H., Yao, M., Lee, T.S., Zhu, Y., Martins-Green, M., Shyy, J.Y. Circ. Res. (2004) [Pubmed]
  17. A common Ile796Val polymorphism of the human SREBP cleavage-activating protein (SCAP) gene. Iwaki, K., Nakajima, T., Ota, N., Emi, M. J. Hum. Genet. (1999) [Pubmed]
  18. Synergistic activation of human LDL receptor expression by SCAP ligand and cytokine oncostatin M. Liu, J., Zhang, F., Li, C., Lin, M., Briggs, M.R. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  19. Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change. Feramisco, J.D., Radhakrishnan, A., Ikeda, Y., Reitz, J., Brown, M.S., Goldstein, J.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  20. Membrane topology of human insig-1, a protein regulator of lipid synthesis. Feramisco, J.D., Goldstein, J.L., Brown, M.S. J. Biol. Chem. (2004) [Pubmed]
  21. Control of lipid metabolism by regulated intramembrane proteolysis of sterol regulatory element binding proteins (SREBPs). Rawson, R.B. Biochem. Soc. Symp. (2003) [Pubmed]
  22. Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi. Nohturfft, A., DeBose-Boyd, R.A., Scheek, S., Goldstein, J.L., Brown, M.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  23. Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles. Adams, C.M., Goldstein, J.L., Brown, M.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  24. The hypocholesterolemic agent LY295427 up-regulates INSIG-1, identifying the INSIG-1 protein as a mediator of cholesterol homeostasis through SREBP. Janowski, B.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  25. Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating protein. Davies, J.P., Ioannou, Y.A. J. Biol. Chem. (2000) [Pubmed]
  26. Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Sever, N., Yang, T., Brown, M.S., Goldstein, J.L., DeBose-Boyd, R.A. Mol. Cell (2003) [Pubmed]
  27. The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients. Durst, R., Jansen, A., Erez, G., Bravdo, R., Butbul, E., Ben Avi, L., Shpitzen, S., Lotan, C., Leitersdorf, E., Defesche, J., Friedlander, Y., Meiner, V., Miserez, A.R. Atherosclerosis (2006) [Pubmed]
  28. Pulse polarographic (constant and increasing) determinations of doxazosin in pharmaceutical tablets. Altiokka, G., Tunçel, M. Journal of pharmaceutical and biomedical analysis. (1998) [Pubmed]
  29. Isolation and radiation hybrid mapping of a highly polymorphic CA repeat sequence at the SREBP cleavage-activating protein (SCAP) locus. Nakajima, T., Ota, N., Kodama, T., Emi, M. J. Hum. Genet. (1999) [Pubmed]
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