SREBP2:SCAP Binds CopII Coat Complex

Stable Identifier
Reaction [omitted]
Cricetulus griseus
SREBF2:SCAP Binds CopII Coat Complex
SVG |   | PPTX  | SBGN
SREBP2:SCAP Binds CopII Coat Complex

SREBP2 (SREBF2 and by inference SREBP1A and SREBP1C) is a transmembrane protein that binds SCAP in the endoplasmic reticulum membrane (Sakai et al. 1997). In the presence of cholesterol or oxysterols SCAP:SREBP2 binds INSIG and is retained in the endoplasmic reticulum (Espenshade et al. 2002, Yabe et al. 2002, Yang et al. 2002, Adams et al. 2003, Dobrosotskaya et al. 2003, Adams et al. 2004, Radhakrishnan et al. 2004, Sun et al. 2005, Sun et al. 2007, Motamed et al. 2011). At cholesterol concentrations below 5 mol% SCAP changes conformation, SCAP:SREBP2 loses interaction with INSIG, binds the CopII coat complex, and is translocated to the Golgi (Adams et al 2004, Feramisco et al. 2005, Radhakrishnan et al. 2008, Motamed et al. 2011).

Literature References
PubMed ID Title Journal Year
21454655 Identification of luminal Loop 1 of Scap protein as the sterol sensor that maintains cholesterol homeostasis

Brown, MS, Wang, ML, Motamed, M, Seemann, J, Zhang, Y, Kwon, HJ, Goldstein, JL

J Biol Chem 2011
12963821 Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles

Brown, MS, Adams, CM, Goldstein, JL

Proc Natl Acad Sci U S A 2003
12242332 Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins

Brown, MS, Goldstein, JL, Yabe, D

Proc Natl Acad Sci U S A 2002
19041766 Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance

Brown, MS, McDonald, JG, Radhakrishnan, A, Goldstein, JL

Cell Metab 2008
15260976 Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain

Brown, MS, Sun, LP, Kwon, HJ, Radhakrishnan, A, Goldstein, JL

Mol Cell 2004
15728349 Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change

Brown, MS, Ikeda, Y, Reitz, J, Feramisco, JD, Radhakrishnan, A, Goldstein, JL

Proc Natl Acad Sci U S A 2005
15452130 Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs

Brown, MS, Adams, CM, De Brabander, JK, Feramisco, JD, Reitz, J, Li, L, Goldstein, JL

J Biol Chem 2004
12202038 Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER

Brown, MS, Aebersold, R, Wright, ME, Espenshade, PJ, Yang, T, Goldstein, JL, Gong, Y, Yabe, D

Cell 2002
9242699 Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein

Brown, MS, Cheng, D, Ho, YK, Nohturfft, A, Sakai, J, Goldstein, JL

J Biol Chem 1997
12842885 Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs

Brown, MS, Rawson, RB, Goldstein, JL, Dobrosotskaya, IY

J Biol Chem 2003
17428919 Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins

Brown, MS, Sun, LP, Seemann, J, Goldstein, JL

Proc Natl Acad Sci U S A 2007
15899885 Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro

Brown, MS, Sun, LP, Li, L, Goldstein, JL

J Biol Chem 2005
12193656 Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER

Li, WP, Espenshade, PJ, Yabe, D

Proc Natl Acad Sci U S A 2002
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