ArticleThe Journal of biological chemistry2013
Point mutation in luminal loop 7 of Scap protein blocks interaction with loop 1 and abolishes movement to Golgi.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Competition between a transmembrane helix on Scap and a membrane cholesterol regulates Scap-Insig interaction and SREBP activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Role of SCAP/SREBP as Central Regulators of Lipid Metabolism in Hepatic Steatosis.International journal of molecular sciences · 2024Review
- Synthesis, function, and regulation of sterol and nonsterol isoprenoids.Frontiers in molecular biosciences · 2022Review
- THADA drives Golgi residency and upregulation of PD-L1 in cancer cells and provides promising target for immunotherapy.Journal for immunotherapy of cancer · 2021Article
- Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing.Cell · 2021Article
- The cellular function of SCAP in metabolic signaling.Experimental & molecular medicine · 2020Review
- A noncanonical PPARγ/RXRα-binding sequence regulates leptin expression in response to changes in adipose tissue mass.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Retrospective on Cholesterol Homeostasis: The Central Role of Scap.Annual review of biochemistry · 2018Review
- CXCL12/CXCR4-Mediated Procollagen Secretion Is Coupled To Cullin-RING Ubiquitin Ligase Activation.Scientific reports · 2018Article
- A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis.The Journal of biological chemistry · 2017Article
- Digenic mutations onOncotarget · 2017Article
- Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis.The Journal of biological chemistry · 2017Article
- Heat Shock Protein 90 Modulates Lipid Homeostasis by Regulating the Stability and Function of Sterol Regulatory Element-binding Protein (SREBP) and SREBP Cleavage-activating Protein.The Journal of biological chemistry · 2017Article
- Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer.Science translational medicine · 2016Article
- Geranylgeranyl-regulated transport of the prenyltransferase UBIAD1 between membranes of the ER and Golgi.Journal of lipid research · 2016Article
- Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS.The Journal of biological chemistry · 2016Article
- Glycogen synthase kinase-3-mediated phosphorylation of serine 73 targets sterol response element binding protein-1c (SREBP-1c) for proteasomal degradation.Bioscience reports · 2015Article
- Nutrient-sensing mechanisms and pathways.Nature · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Scap is a polytopic protein of the endoplasmic reticulum (ER) that controls cholesterol homeostasis by transporting sterol regulatory element-binding proteins (SREBPs) from the ER to the Golgi complex. Scap has eight transmembrane helices (TM) joined by four small hydrophilic loops and three large loops. Two of the large loops (Loops 1 and 7) are in the ER lumen, and the other large loop (Loop 6) faces the cytosol where it binds COPII proteins that initiate transport to Golgi. Cholesterol binding to Loop 1 alters the configuration of Loop 6, precluding COPII binding and preventing the exit of Scap from the ER. Here, we create a point mutation (Y640S) in luminal Loop 7 that prevents Scap movement to Golgi. Trypsin cleavage assays show that Loop 6 of Scap(Y640S) is always in the configuration that precludes COPII binding, even in the absence of cholesterol. When expressed separately by co-transfection, the NH2-terminal portion of Scap (containing TM helices 1-6, including Loop 1) binds to the COOH-terminal portion (containing TM helices 7-8 and Loop 7) as determined by co-immunoprecipitation. This binding does not occur when Loop 7 contains the Y640S mutation. Co-immunoprecipitation is also abolished by a point mutation in Loop 1 (Y234A) that also prevents Scap movement. These data suggest that Scap Loop 1 must interact with Loop 7 to maintain Loop 6 in the configuration that permits COPII binding. These results help explain the operation of Scap as a sterol sensor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.