Disease relevance of OSBPL1A

• The most abundantly expressed new gene, ORP-1, was transcribed at strikingly high levels in the cortical areas of human brain and displayed sterol-regulated expression in a cultured human neuroblastoma cell line [1].

High impact information on OSBPL1A

• Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides [2].
• Oxysterols regulate cellular functions by binding to oxysterol binding protein and oxysterol binding protein-related proteins [3].
• The results suggest that the two forms of ORP1 are functionally distinct and that ORP1L is involved in control of cellular lipid metabolism [4].
• Two variants of OSBP-related protein (ORP) 1 have been identified: a short one that consists of the carboxy-terminal ligand binding domain only (ORP1S, 437 aa) and a longer N-terminally extended form (ORP1L, 950 aa) encompassing three ankyrin repeats and a pleckstrin homology domain (PHD) [4].
• Phenotypes associated with overexpression of ORP2 in yeast were a dramatic decrease in cell growth and a block in Golgi-derived vesicle transport distinct from that of ORP1 [5].

Biological context of OSBPL1A

• A second OSBPL1 transcript (OSBPL1B) contains 15 additional upstream exons, with a deduced peptide containing a pleckstrin homology domain [6].
• Prompted by the multitude of OSBP-related genes in the yeast genome, we carried out a search for human expressed sequence tags (ESTs) displaying homology to the sterol-binding domain of OSBP [1].
• Families of genes/proteins with sequence homology to oxysterol binding protein have been identified in eukaryotes from yeast to man, indicating that these proteins, denoted as oxysterol binding protein-related proteins (ORPs), serve a fundamental purpose conserved in evolution [7].
• Studies on oxysterol binding protein and oxysterol binding protein-related proteins should lead to new understandings about sterol-regulated signal transduction and membrane trafficking pathways in cells [3].
• Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and regulates Akt phosphorylation [8].

Anatomical context of OSBPL1A

• This indicates that ORP-1 may play an important role in maintaining the sterol balance in cells of the central nervous system [1].

Other interactions of OSBPL1A

• However, two of the peptides, OSBPL2 and OSBPL1A, consist of the OSBP domain only [6].
• This revealed a minimum of six novel OSBP-related proteins, designated ORP-1 to ORP-6 [1].
• The ORP-1 and -2 mRNA expression levels were similar to or higher than that of OSBP while the ORP-3 to -6 mRNAs were detected at lower levels in specific tissues [1].
• Assays for interaction between Rab7 and oxysterol binding protein related protein 1L (ORP1L) [9].

References