ArticleThe Journal of biological chemistry2011
Identification of luminal Loop 1 of Scap protein as the sterol sensor that maintains cholesterol homeostasis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 97 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
- Computational Elucidation of Sterol Recognition by SREBP Cleavage Activatory Protein.Journal of chemical information and modeling · 2025Article
- A cholesterol-binding bacterial toxin provides a strategy for identifying a specific Scap inhibitor that blocks lipid synthesis in animal cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Direct binding to sterols accelerates endoplasmic reticulum-associated degradation of HMG CoA reductase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Role of SCAP/SREBP as Central Regulators of Lipid Metabolism in Hepatic Steatosis.International journal of molecular sciences · 2024Review
- Nutrient sensors and their crosstalk.Experimental & molecular medicine · 2023Review
- Robust homeostasis of cellular cholesterol is a consequence of endogenous antithetic integral control.Frontiers in cell and developmental biology · 2023Article
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- The role of cholesterol binding in the control of cholesterol by the Scap-Insig system.European biophysics journal : EBJ · 2022Article
- Sterol regulation of developmental and oncogenic Hedgehog signaling.Biochemical pharmacology · 2022Review
- Synthesis, function, and regulation of sterol and nonsterol isoprenoids.Frontiers in molecular biosciences · 2022Review
- Photoaffinity labelling strategies for mapping the small molecule-protein interactome.Organic & biomolecular chemistry · 2021Review
- Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing.Cell · 2021Article
- Sterol-resistant SCAP Overexpression in Vascular Smooth Muscle Cells Accelerates Atherosclerosis by Increasing Local Vascular Inflammation through Activation of the NLRP3 Inflammasome in Mice.Aging and disease · 2021Article
- Regulation of lipid metabolism by the unfolded protein response.Journal of cellular and molecular medicine · 2021Review
- The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER-Golgi membrane contact sites.The Journal of cell biology · 2021Article
- Structure, membrane topology and influence of cholesterol of the membrane proximal region: transmembrane helical anchor sequence of gp41 from HIV.Scientific reports · 2020Article
- Transcription factors activated through RIP (regulated intramembrane proteolysis) and RAT (regulated alternative translocation).The Journal of biological chemistry · 2020Review
- The cellular function of SCAP in metabolic signaling.Experimental & molecular medicine · 2020Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Cellular cholesterol homeostasis is maintained by Scap, an endoplasmic reticulum (ER) protein with eight transmembrane helices. In cholesterol-depleted cells, Scap transports sterol regulatory element-binding proteins (SREBPs) to the Golgi, where the active fragment of SREBP is liberated by proteases so that it can activate genes for cholesterol synthesis. When ER cholesterol increases, Scap binds cholesterol, and this changes the conformation of cytosolic Loop 6, which contains the binding site for COPII proteins. The altered conformation precludes COPII binding, abrogating movement to the Golgi. Consequently, cholesterol synthesis declines. Here, we identify the cholesterol-binding site on Scap as Loop 1, a 245-amino acid sequence that projects into the ER lumen. Recombinant Loop 1 binds sterols with a specificity identical to that of the entire Scap membrane domain. When tyrosine 234 in Loop 1 is mutated to alanine, Loop 6 assumes the cholesterol-bound conformation, even in sterol-depleted cells. As a result, full-length Scap(Y234A) cannot mediate SREBP processing in transfected cells. These results indicate that luminal Loop 1 of Scap controls the conformation of cytosolic Loop 6, thereby determining whether cells produce cholesterol.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.