OSBPs transport 25OH-CHOL from ER membrane to plasma membrane

Stable Identifier
R-HSA-8867667
Type
Reaction
Species
Homo sapiens
Compartment
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Oxysterol-binding proteins (OSBPs) and OSBP-related proteins (ORPs) comprise a 12-member mammalian gene family of intracellular lipid receptors which bind oxygenated cholesterol derivatives and are thought to mediate sterol and phospholipid synthesis (Olkkonen & Li 2013, Weber-Boyvat et al. 2013). A conserved OSBP homology domain (OHD) binds sterols and lipids and a pleckstrin homology (PH) domain and two phenylalanines in an acidic tract (FFAT) motif mediate interaction with organelle membranes (Olkkonen 2015). The primary function of the protein family remains unresolved. Most (OSBPL2,3,6,7,9 and 1A), if not all of the OSBPLs are thought to bind and coordinate distribution of oxygenated cholesterol derivatives such as 25-hydroxycholesterol (25OH-CHOL). Oxysterol-binding protein 2 (OSBP2, aka ORP4) is primarily expressed in brain, and to a lesser extent in heart, skeletal muscle, spleen and kidney. It has a diffuse cytoplasmic localisation profile and is a high-affinity 25OH-CHOL binding protein (Wang et al. 2002, Suchanek et al. 2007). RNAi silencing of all OSBP2 variants in HEK293 and HeLa cells resulted in growth arrest but not cell death, suggesting OSBP2 is essential for cell proliferation and survival (Charman et al. 2014).

Literature References
PubMed ID Title Journal Year
17428193 The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket

Hynynen, R, Radzikowska, A, Olkkonen, VM, Johansson, M, Saarinen, H, Suchanek, M, Wohlfahrt, G, Lehto, M, Thiele, C

Biochem. J. 2007
23428468 Oxysterol-binding proteins: functions in cell regulation beyond lipid metabolism

Olkkonen, VM, Zhong, W, Weber-Boyvat, M, Yan, D

Biochem. Pharmacol. 2013
23830809 Oxysterol-binding proteins: sterol and phosphoinositide sensors coordinating transport, signaling and metabolism

Olkkonen, VM, Li, S

Prog. Lipid Res. 2013
26715851 OSBP-Related Protein Family in Lipid Transport Over Membrane Contact Sites

Olkkonen, VM

Lipid Insights 2015
11802775 Oxysterol-binding-protein (OSBP)-related protein 4 binds 25-hydroxycholesterol and interacts with vimentin intermediate filaments

Wang, C, JeBailey, L, Ridgway, ND

Biochem. J. 2002
24742681 Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival

Kreplak, L, Colbourne, TR, Charman, M, Pietrangelo, A, Ridgway, ND

J. Biol. Chem. 2014
Participants
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Catalyst Activity

sterol transporter activity of OSBPs [cytosol]

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