Abstract
Oxysterols are oxygenated derivatives of cholesterol that have a number of biological effects and play a key role in the maintenance of the body cholesterol balance. In this study, we describe the cDNA sequences and genomic structures of the recently identified human oxysterol-binding protein (OSBP)-related protein (ORP) family (Laitinen, S. et al. 1999. J. Lipid Res. 40: 2204–2211). The family now includes 12 genes/proteins, which can be divided into six distinct subfamilies. The ORP have two major structural features: a highly conserved OSBP-type sterol-binding domain in the C-terminal half and a pleckstrin homology domain present in the N-terminal region of most family members. Several ORP genes are present in S. cerevisiae, D. melanogaster, and C. elegans, suggesting that the protein family has functions of fundamental importance in the eukaryotic kingdom. Analysis of ORP mRNA levels in unloaded or acetylated LDL-loaded human macrophages revealed that the expression of ORP genes was not significantly affected by the loading, with the exception of ORP6, which was up-regulated 2-fold. The present study summarizes the basic characteristics of the OSBP-related gene/protein family in humans, and provides tools for functional analysis of the encoded proteins. —Lehto, M., S. Laitinen, G. Chinetti, M. Johansson, C. Ehnholm, B. Staels, E. Ikonen, and V. M. Olkkonen. The OSBP-related protein family in humans.
Highlights
Oxysterols are oxygenated derivatives of cholesterol that have a number of biological effects and play a key role in the maintenance of the body cholesterol balance
Oxysterols bind to the steroidogenic factor 1 (SF-1), which regulates the expression of a number of genes involved in steroidogenesis and cholesterol metabolism (12 –15)
We recently identified a family of novel human OSBPrelated proteins (ORP) at the level of contigs generated from expressed sequence tags (EST) [30]
Summary
Oxysterols are oxygenated derivatives of cholesterol that have a number of biological effects and play a key role in the maintenance of the body cholesterol balance. We describe the cDNA sequences and genomic structures of the recently identified human oxysterol-binding protein (OSBP)-related protein (ORP) family When activated by oxysterols [3], the liver X receptors (LXR) regulate the expression of several genes in key positions in the maintenance of the body-cholesterol balance. These include genes involved in cholesterol absorption in the gut [4], cholesterol efflux from peripheral cells [4,5,6], synthesis of fatty acids [7, 8], remodeling of lipoproteins in the circulation [9], and the bile acid synthetic pathway [10, 11]. We report the cDNA sequences and exon-intron organization of human genes belonging to the OSBP gene family (which at present, consists of 12 members), and summarize data on the tissue expression of the ORP
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