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Regulation of cholesterol biosynthesis by SREBP (SREBF)

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-1655829

PubChem

R-HSA-1655829

Description

Sterol regulatory element binding proteins (SREBPs, SREBFs) respond to low cholesterol concentrations by transiting to the nucleus and activating genes involved in cholesterol and lipid biosynthesis (reviewed in Brown and Goldstein 2009, Osborne and Espenshade 2009, Weber et al. 2004).
Newly synthesized SREBPs are transmembrane proteins that bind SCAP in the endoplasmic reticulum (ER) membrane. SCAP binds cholesterol which causes a conformational change that allows SCAP to interact with INSIG, retaining the SCAP:SREBP complex in the ER. INSIG binds oxysterols, which cause INSIG to bind SCAP and retain SCAP:SREBP in the endoplasmic reticulum.
In low cholesterol (below about 5 mol%) SCAP no longer interacts with cholesterol or INSIG and binds Sec24 of the CopII coat complex instead. Thus SCAP:SREBP transits with the CopII complex from the ER to the Golgi. In the Golgi SREBP is cleaved by S1P and then by S2P, releasing the N-terminal fragment of SREBP into the cytosol. The N-terminal fragment is imported to the nucleus by importin-beta and then acts with other factors, such as SP1 and NF-Y, to activate transcription of target genes. Targets of SREBP include the genes encoding all enzymes of cholesterol biosynthesis and several genes involved in lipogenesis. SREBP2 most strongly activates cholesterol biosynthesis while SREBP1C most strongly activates lipogenesis.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 10** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O43462	Membrane-bound transcription factor site-2 protease	MBTPS2 S2P	view
O94855	Protein transport protein Sec24D	KIAA0755 SEC24D	view
O95486	Protein transport protein Sec24A	SEC24A	view
O95487	Protein transport protein Sec24B	SEC24B	view
P53992	Protein transport protein Sec24C	KIAA0079 SEC24C	view
Q12770	Sterol regulatory element-binding protein cleavage-activating protein	KIAA0199 PSEC0227 SCAP	view
Q12772	Sterol regulatory element-binding protein 2	BHLHD2 SREBF2 SREBP2	view
Q14703	Membrane-bound transcription factor site-1 protease	KIAA0091 MBTPS1 S1P SKI1	view
Q14974	Importin subunit beta-1	KPNB1 NTF97	view
Q15436	Protein transport protein Sec23A	SEC23A	view

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