Alternative titles; symbols
HGNC Approved Gene Symbol: OBP2A
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38) : 9:135,546,126-135,549,969 (from NCBI)
Odorant-binding protein, which is found in nasal epithelium, selectively binds odorants. Pevsner et al. (1988) cloned and sequenced rat OBP cDNAs. RNA blot analysis confirmed the localization of OBP mRNA in the nasal epithelium. OBP was found to have 33% amino acid identity to alpha-2-microglobulin, a secreted plasma protein of the male rat (Unterman et al., 1981). Apolipoprotein D (107740) is a probable carrier for cholesterol, and retinol-binding protein (180290) transfers retinol from plasma to the pigment epithelium of the retina. Since these other members of the alpha-2-microglobulin superfamily bind and transport hydrophobic ligands, OBP probably binds and carries odorants within the nasal epithelium to putative olfactory receptors. In the rat, Dear et al. (1991) cloned a putative odorant-binding protein, which they referred to as OBP II. It showed significant homology to the VEG protein, which is thought to be involved in taste transduction. Raming et al. (1993) identified new members of the gene family encoding putative odorant receptors and demonstrated that they are transcribed in olfactory receptor neurons. Furthermore, the receptor-encoding cDNA was expressed in nonneuronal surrogate cells, which generated second messenger responses upon stimulation with appropriate odorants, indicating that the receptors recognize odorants and couple to G proteins of the host cells.
Lipocalins are carrier proteins for hydrophobic molecules in many biologic fluids. In the oral sphere (nasal mucus, saliva, tears), they have an environmental biosensor function and are involved in the detection of odors and pheromones. Lacazette et al. (2000) reported the identification of human lipocalins involved in odorant binding. They corresponded to a gene family located on 9q34 produced by genomic duplication: 2 odorant-binding protein genes (OBP2A and OBP2B, 604606), the tear lipocalin LCN1 gene (151675), and 2 LCN1 pseudogenes. Although 95% similar in sequence, the 2 OBP2 genes were differentially expressed in secretory structures. OBP2A was strongly expressed in the nasal structures, salivary and lachrymal glands, and lung, therefore having an oral-sphere profile. OBP2B was more strongly expressed in genital-sphere organs such as the prostate and mammary glands. Both were expressed in the placenta and male vas deferens. Surprisingly, alternatively spliced mRNAs resulting in proteins with different C termini were generated from each of the 2 genes. Based on the proposed history of successive genomic duplication, Lacazette et al. (2000) demonstrated the recruitment of exons within intronic DNA generating diversity. This was consistent with a positive selection pressure in vertebrate evolution in the intron-late hypothesis.
Lacazette et al. (2000) determined that the OBP2A gene contains 7 exons, in a structure consistent with genes of the lipocalin family.
Lacazette et al. (2000) identified the OBP2A gene on chromosome 9q34.
Briand et al. (2002) found that human OBPs were expressed in the mucus covering the olfactory cleft, where the sensory olfactory epithelium is located, but not in mucus covering the septum and the lower turbinate. Recombinant OBP2A was expressed in yeast as a monomer containing a disulfide bond characteristic of other vertebrate OBPs. By measuring the displacement of several fluorescent probes, Briand et al. (2002) showed that OBP2A binds numerous odorants of diverse chemical structure. Highest affinity was measured for aldehydes and large fatty acids. A computed 3-dimensional model revealed 2 lysyl residues of the binding pocket that could account for the increased affinity for aldehydes.
Briand, L., Eloit, C., Nespoulous, C., Bezirard, V., Huet, J.-C., Henry, C., Blon, F., Trotier, D., Pernollet, J.-C. Evidence of an odorant-binding protein in the human olfactory mucus: location, structural characterization, and odorant-binding properties. Biochemistry 41: 7241-7252, 2002. [PubMed: 12044155] [Full Text: https://doi.org/10.1021/bi015916c]
Dear, T. N., Campbell, K., Rabbitts, T. H. Molecular cloning of putative odorant-binding and odorant-metabolizing proteins. Biochemistry 30: 10376-10382, 1991. [PubMed: 1931961] [Full Text: https://doi.org/10.1021/bi00107a003]
Lacazette, E., Gachon, A. M., Pitiot, G. A novel human odorant-binding protein gene family resulting from genomic duplicons at 9q34: differential expression in the oral and genital spheres. Hum. Molec. Genet. 9: 289-301, 2000. [PubMed: 10607840] [Full Text: https://doi.org/10.1093/hmg/9.2.289]
Pevsner, J., Reed, R. R., Feinstein, P. G., Snyder, S. H. Molecular cloning of odorant-binding protein: member of a ligand carrier family. Science 241: 336-339, 1988. [PubMed: 3388043] [Full Text: https://doi.org/10.1126/science.3388043]
Raming, K., Krieger, J., Strotmann, J., Boekhoff, I., Kubick, S., Baumstark, C., Breer, H. Cloning and expression of odorant receptors. Nature 361: 353-356, 1993. [PubMed: 7678922] [Full Text: https://doi.org/10.1038/361353a0]
Unterman, R. D., Lynch, K. R., Nakhasi, H. L., Dolan, K. P., Hamilton, J. W., Cohn, D. V., Feigelson, P. Cloning and sequence of several alpha-2-microglobulin cDNAs. Proc. Nat. Acad. Sci. 78: 3478-3482, 1981. [PubMed: 6167987] [Full Text: https://doi.org/10.1073/pnas.78.6.3478]