Gene Symbol: Scap
Description: SREBF chaperone
Alias: 9530044G19, mKIAA0199, sterol regulatory element-binding protein cleavage-activating protein, SREBP cleavage activating protein, Sreb cleavage-activating protein, scap
Species: mouse
Products:     Scap

Top Publications

  1. Korstanje R, Albers J, Wolfbauer G, Li R, Tu A, Churchill G, et al. Quantitative trait locus mapping of genes that regulate phospholipid transfer activity in SM/J and NZB/BlNJ inbred mice. Arterioscler Thromb Vasc Biol. 2004;24:155-60 pubmed
    ..We identified five significant loci involved in PLTP activity in the mouse and provided supporting evidence for the candidacy of Nr1h4 and Apof as the genes underlying Pltpq2. ..
  2. Matsuda M, Korn B, Hammer R, Moon Y, Komuro R, Horton J, et al. SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes Dev. 2001;15:1206-16 pubmed
    ..b>SCAP (SREBP cleavage-activating protein) is a sterol-regulated escort protein that transports SREBPs from their site of ..
  3. Kuriyama H, Liang G, Engelking L, Horton J, Goldstein J, Brown M. Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver. Cell Metab. 2005;1:41-51 pubmed
    The escort protein SCAP transports SREBPs from ER to Golgi where the active domains are released to activate genes for fatty acid (FA) and cholesterol synthesis...
  4. Besnard V, Wert S, Stahlman M, Postle A, Xu Y, Ikegami M, et al. Deletion of Scap in alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts. J Biol Chem. 2009;284:4018-30 pubmed publisher
    ..To identify the role of SREBPs in the lung, we conditionally deleted the SREBP cleavage-activating protein gene, Scap, in respiratory epithelial cells (ScapDelta/Delta) in vivo. Prior to birth (E18...
  5. Rong S, Cortés V, Rashid S, Anderson N, McDonald J, Liang G, et al. Expression of SREBP-1c Requires SREBP-2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice. elife. 2017;6: pubmed publisher
    ..These studies demonstrate that cholesterol and FA synthesis in hepatocytes are coupled and that flux through the cholesterol biosynthetic pathway is required for the maximal SREBP-1c expression and high rates of FA synthesis. ..
  6. Tarling E, Ahn H, de Aguiar Vallim T. The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2. Arterioscler Thromb Vasc Biol. 2015;35:787-95 pubmed publisher
    ..Finally, we show that FXR-dependent induction of both Srebp-2 and miR-33 is ablated in Scap(-/-) mice that lack nuclear SREBP-2...
  7. Suzuki R, Ferris H, Chee M, Maratos Flier E, Kahn C. Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function. PLoS Biol. 2013;11:e1001532 pubmed publisher
    The sterol sensor SCAP is a key regulator of SREBP-2, the major transcription factor controlling cholesterol synthesis...
  8. Camargo N, Brouwers J, Loos M, Gutmann D, Smit A, Verheijen M. High-fat diet ameliorates neurological deficits caused by defective astrocyte lipid metabolism. FASEB J. 2012;26:4302-15 pubmed publisher
    ..we generated mice in which the sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) was deleted from astrocytes using cre/lox technology...
  9. Verdier V, Csárdi G, de Preux Charles A, Medard J, Smit A, Verheijen M, et al. Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways. Glia. 2012;60:751-60 pubmed publisher
    ..By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54...

More Information


  1. Verheijen M, Camargo N, Verdier V, Nadra K, de Preux Charles A, Medard J, et al. SCAP is required for timely and proper myelin membrane synthesis. Proc Natl Acad Sci U S A. 2009;106:21383-8 pubmed publisher
    ..lipid synthesis is regulated by sterol regulatory element-binding protein (SREBP) cleavage activation protein (SCAP), an activator of SREBPs...
  2. Beigneux A, Kosinski C, Gavino B, Horton J, Skarnes W, Young S. ATP-citrate lyase deficiency in the mouse. J Biol Chem. 2004;279:9557-64 pubmed
    ..The Acly knockout allele is useful for identifying cell types with a high demand for acetyl-CoA synthesis. ..
  3. Camargo N, Goudriaan A, van Deijk A, Otte W, Brouwers J, Lodder H, et al. Oligodendroglial myelination requires astrocyte-derived lipids. PLoS Biol. 2017;15:e1002605 pubmed publisher
    ..inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in ..
  4. van Deijk A, Camargo N, Timmerman J, Heistek T, Brouwers J, Mogavero F, et al. Astrocyte lipid metabolism is critical for synapse development and function in vivo. Glia. 2017;65:670-682 pubmed publisher
    ..Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes...
  5. Papazyan R, Sun Z, Kim Y, Titchenell P, Hill D, Lu W, et al. Physiological Suppression of Lipotoxic Liver Damage by Complementary Actions of HDAC3 and SCAP/SREBP. Cell Metab. 2016;24:863-874 pubmed publisher
    ..Here we show that inactivation of SREBP by hepatic deletion of SREBP cleavage activating protein (SCAP) abrogates the increase in lipogenesis caused by loss of HDAC3, but fatty acid oxidation ..
  6. Shimizu Albergine M, Van Yserloo B, Golkowski M, Ong S, Beavo J, Bornfeldt K. SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP. Proc Natl Acad Sci U S A. 2016;113:E5685-93 pubmed publisher MA10 Leydig cells suggested that cAMP regulates multiple steps in these processes, including activation of the SCAP/SREBP pathway...
  7. York A, Williams K, Argus J, Zhou Q, Brar G, Vergnes L, et al. Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell. 2015;163:1716-29 pubmed publisher
    ..Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity. ..
  8. Zhang Y, Papazyan R, Damle M, Fang B, Jager J, Feng D, et al. The hepatic circadian clock fine-tunes the lipogenic response to feeding through ROR?/?. Genes Dev. 2017;31:1202-1211 pubmed publisher
    ..This highlights the importance of time of day as a consideration in the treatment of liver metabolic disorders. ..
  9. Hashimoto M, Kobayashi K, Yamazaki M, Kazuki Y, Takehara S, Oshimura M, et al. Cyp3a deficiency enhances androgen receptor activity and cholesterol synthesis in the mouse prostate. J Steroid Biochem Mol Biol. 2016;163:121-8 pubmed publisher
    ..In addition, the protein expression levels of SREBP cleavage-activating protein (SCAP), mRNA expression levels of SREBP2 target genes and total cholesterol contents were increased in the prostates of ..
  10. Chen W, Li S, Yu H, Liu X, Huang L, Wang Q, et al. ER Adaptor SCAP Translocates and Recruits IRF3 to Perinuclear Microsome Induced by Cytosolic Microbial DNAs. PLoS Pathog. 2016;12:e1005462 pubmed publisher
    ..How IRF3 is recruited onto the STING signalosome remains unknown. We report here that silencing of the ER adaptor SCAP markedly impairs the IRF3-responsive gene expression induced by STING...
  11. McFarlane M, Cantoria M, Linden A, January B, Liang G, Engelking L. Scap is required for sterol synthesis and crypt growth in intestinal mucosa. J Lipid Res. 2015;56:1560-71 pubmed publisher
    SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and ..
  12. Wittenburg H, Lammert F, Wang D, Churchill G, Li R, Bouchard G, et al. Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice. Physiol Genomics. 2002;8:67-77 pubmed
    ..According to standard nomenclature, the gallstone QTL on chromosome 9 is named Lith5. ..
  13. Kidani Y, Elsaesser H, Hock M, Vergnes L, Williams K, Argus J, et al. Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat Immunol. 2013;14:489-99 pubmed publisher
    ..Our studies provide insights into the molecular signals that underlie the metabolic reprogramming of CD8(+) T cells during the transition from quiescence to activation. ..
  14. Williams K, Argus J, Zhu Y, Wilks M, Marbois B, York A, et al. An essential requirement for the SCAP/SREBP signaling axis to protect cancer cells from lipotoxicity. Cancer Res. 2013;73:2850-62 pubmed publisher
    ..These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. ..
  15. Sallam T, Jones M, Gilliland T, Zhang L, Wu X, Eskin A, et al. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis. Nature. 2016;534:124-8 pubmed publisher
    ..These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis. ..
  16. Rudolph M, Monks J, Burns V, Phistry M, Marians R, Foote M, et al. Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium. Am J Physiol Endocrinol Metab. 2010;299:E918-27 pubmed publisher
    ..of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage-activating protein (SCAP), the SREBF escort protein...
  17. Yabe D, Brown M, Goldstein J. Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc Natl Acad Sci U S A. 2002;99:12753-8 pubmed publisher
    ..reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the ..
  18. Horton J, Shah N, Warrington J, Anderson N, Park S, Brown M, et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A. 2003;100:12027-32 pubmed
    ..and in mice that lack all three nuclear SREBPs as a result of gene knockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SREBPs...
  19. Yang T, Espenshade P, Wright M, Yabe D, Gong Y, Aebersold R, et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 2002;110:489-500 pubmed
    ..we identify INSIG-1 as an ER protein that binds the sterol-sensing domain of SREBP cleavage-activating protein (SCAP) and facilitates retention of the SCAP/SREBP complex in the ER...
  20. Moon Y, Liang G, Xie X, Frank Kamenetsky M, Fitzgerald K, Koteliansky V, et al. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab. 2012;15:240-6 pubmed publisher
    ..Here, we show that steatosis in insulin-resistant ob/ob mice was abolished by deletion of Scap, an escort protein necessary for generating nuclear isoforms of all three SREBPs...
  21. Tang J, Li J, Qi W, Qiu W, Li P, Li B, et al. Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques. Cell Metab. 2011;13:44-56 pubmed publisher
    ..molecule, betulin, that specifically inhibited the maturation of SREBP by inducing interaction of SREBP cleavage activating protein (SCAP) and Insig...
  22. Li J, Nanayakkara A, Jun J, Savransky V, Polotsky V. Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia. Physiol Genomics. 2007;31:273-80 pubmed
    ..We utilized mice with a conditional knockout of SREBP cleavage-activating protein (SCAP) in the liver (L-Scap- mice), which exhibit low levels of an active nuclear isoform of SREBP-1 (nSREBP-1)...
  23. Bridges J, Schehr A, Wang Y, Huo L, Besnard V, Ikegami M, et al. Epithelial SCAP/INSIG/SREBP signaling regulates multiple biological processes during perinatal lung maturation. PLoS ONE. 2014;9:e91376 pubmed publisher
    ..Genome wide mRNA expression profiling of lung tissue from transgenic mice with epithelial-specific deletions of Scap (Scap(?/?), resulting in inactivation of SREBP signaling) or Insig1 and Insig2 (Insig1/2(?/?), resulting in ..