Alternative titles; symbols
HGNC Approved Gene Symbol: OSBPL5
Cytogenetic location: 11p15.4 Genomic coordinates (GRCh38): 11:3,087,107-3,165,310 (from NCBI)
OSBPL5 is a member of the OSBP family of intracellular lipid receptors. For background information on OSBPs, see OSBP2 (606729).
By EST database searching for sequences homologous to OSBP (167040), followed by RT-PCR, Laitinen et al. (1999) identified 6 OSBP-related proteins, including OSBPL5, which they called ORP5. Northern blot analysis revealed ubiquitous but low expression of a 4.0-kb transcript. Highest expression was in thymus and peripheral blood leukocytes.
By screening for cDNAs with the potential to encode large proteins expressed in brain, Nagase et al. (2000) identified a cDNA encoding OSBPL5, which they called KIAA1534. The deduced 863-amino acid protein was predicted to be 34% identical to mouse Osbp. RT-PCR analysis detected wide expression that was strongest in ovary and in various brain regions.
Lehto et al. (2001) used RT-PCR analysis with specific primers to isolate a full-length cDNA encoding ORP5. Sequence analysis predicted that the 879-amino acid protein contains a C-terminal sterol-binding (SB) domain of approximately 400 residues that includes the OSBP motif (EQVSHHPP). It has a pleckstrin homology (PH) domain in its N terminus. OSBPL5 is 78% and 88% identical to OSBPL8 (606736) in the SB and PH domains, respectively.
Jaworski et al. (2001) cloned multiple OSBPs, including OSBPL5. RT-PCR analysis detected wide but weak expression that was highest in retinal pigment epithelium choroid, pineal gland, and cultured retinal pigment epithelial cells.
By PCR and 5-prime RACE of a heart cDNA library, Higashimoto et al. (2002) cloned OSBPL5, which they called OBPH1. The deduced protein contains 879 amino acids. Northern blot analysis detected a 4.0-kb transcript with highest expression in heart and brain, moderate expression in placenta, lung, kidney, skeletal muscle, and pancreas, and weak expression in liver. An additional 2.5-kb transcript was detected at moderate levels in heart and skeletal muscle. In mouse, Obph1 expression was ubiquitous, but its pattern of expression differed from that found in human tissues. Higashimoto et al. (2002) examined the imprinting status of OBPH1 in both mouse and human tissues and determined that its expression was imprinted in placenta but not in other tissues in both species. There was no relation between the imprinting status and the methylation status of the CpG island in either species.
Maeda et al. (2013) developed an integrated approach that combined protein fractionation and lipidomics to characterize the lipid transfer protein-lipid complexes formed in vivo. The procedure applied to S. cerevisiae found that Osh6 and Osh7 have an unexpected specificity for phosphatidylserine. In vivo, they participate in phosphatidylserine homeostasis and the transport of this lipid to the plasma membrane. The structure of Osh6 bound to phosphatidylserine revealed unique features that are conserved among other metazoan oxysterol-binding proteins and are required for phosphatidylserine recognition. Maeda et al. (2013) stated that their findings represented the first direct evidence for the nonvesicular transfer of phosphatidylserine from its site of biosynthesis (the endoplasmic reticulum) to its site of biologic activity (the plasma membrane). Maeda et al. (2013) described a subfamily of oxysterol-binding proteins, including human ORP5 and ORP10 (606738), that transfer phosphatidylserine, and proposed mechanisms of action for a protein family that is involved in several human pathologies such as cancer, dyslipidemia, and metabolic syndrome.
Chung et al. (2015) found that ORP5 and ORP8 (606736) tether the endoplasmic reticulum to the plasma membrane via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their oxysterol binding protein-related domains harbored either PI4P or phosphatidylserine and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the endoplasmic reticulum and the plasma membrane, thus delivering PI4P to the endoplasmic reticulum-localized PI4P phosphatase Sac1 (606569) for degradation and phosphatidylserine from the endoplasmic reticulum to the plasma membrane. This exchange helps to control plasma membrane PI4P levels and selectively enrich phosphatidylserine in the plasma membrane.
By database analysis, Lehto et al. (2001) determined that the OSBPL5 gene contains 21 exons. Jaworski et al. (2001) found that it contains 22 exons.
By radiation hybrid analysis, Nagase et al. (2000) mapped the OSBPL5 gene to chromosome 11. By database analysis, Lehto et al. (2001) also mapped the gene to chromosome 11. Jaworski et al. (2001) refined the localization to 11p15.4.
Higashimoto et al. (2002) stated that the mouse Osbpl5 gene maps to a region of chromosome 7F4-F5 that shares homology of synteny with human chromosome 11p15.5.
Chung, J., Torta, F., Masai, K., Lucast, L., Czapla, H., Tanner, L. B., Narayanaswamy, P., Wenk, M. R., Nakatsu, F., De Camilli, P. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts. Science 349: 428-432, 2015. [PubMed: 26206935] [Full Text: https://doi.org/10.1126/science.aab1370]
Higashimoto, K., Soejima, H., Yatsuki, H., Joh, K., Uchiyama, M., Obata, Y., Ono, R., Wang, Y., Xin, Z., Zhu, X., Masuko, S., Ishino, F., Hatada, I., Jinno, Y., Iwasaka, T., Katsuki, T., Mukai, T. Characterization and imprinting status of OBPH1/Obph1 gene: implications for an extended imprinting domain in human and mouse. Genomics 80: 575-584, 2002. Note: Erratum: Genomics 81, 346 only, 2003. [PubMed: 12504849] [Full Text: https://doi.org/10.1006/geno.2002.7006]
Jaworski, C. J., Moreira, E., Li, A., Lee, R., Rodriguez, I. R. A family of 12 human genes containing oxysterol-binding domains. Genomics 78: 185-196, 2001. [PubMed: 11735225] [Full Text: https://doi.org/10.1006/geno.2001.6663]
Laitinen, S., Olkkonen, V. M., Ehnholm, C., Ikonen, E. Family of human oxysterol binding protein (OSBP) homologues: a novel member implicated in brain sterol metabolism. J. Lipid Res. 40: 2204-2211, 1999. [PubMed: 10588946] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0022-2275(20)32095-2]
Lehto, M., Laitinen, S., Chinetti, G., Johansson, M., Ehnholm, C., Staels, B., Ikonen, E., Olkkonen, V. M. The OSBP-related protein family in humans. J. Lipid Res. 42: 1203-1213, 2001. [PubMed: 11483621] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0022-2275(20)31570-4]
Maeda, K., Anand, K., Chiapparino, A., Kumar, A., Poletto, M., Kaksonen, M., Gavin, A.-C. Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins. Nature 501: 257-261, 2013. [PubMed: 23934110] [Full Text: https://doi.org/10.1038/nature12430]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 143-150, 2000. [PubMed: 10819331] [Full Text: https://doi.org/10.1093/dnares/7.2.143]