HGNC Approved Gene Symbol: NPY5R
Cytogenetic location: 4q32.2 Genomic coordinates (GRCh38): 4:163,343,892-163,352,403 (from NCBI)
The NPY5R gene encodes a receptor for neuropeptide Y (NPY), a neuropeptide involved in physiologic control of energy homeostasis. NPY5R is thought to have a role in feeding regulation (Hu et al., 1996, Ishihara et al., 2006).
Gerald et al. (1996) cloned a novel Y-type receptor that they termed Y5 from rat hypothalamus and reported that it encodes a 456-amino acid protein with less than 35% overall identity to known Y-type receptors. They identified a human Y5 homolog in the GenBank database having 87% overall identity with rat Y5.
Hu et al. (1996) cloned the rat and human Y5 receptors from a rat hypothalamus cDNA library and a human genomic library, respectively. Both genes encode 445-amino acid polypeptides with 7 putative transmembrane domains. The rat and human Y5 protein sequences share 88% identity and show 30 to 33% identity to other NPY receptor subtypes. Northern blot analysis revealed that the gene is expressed as a 2.6-kb mRNA in the brain but in no other tissues tested. Hu et al. (1996) also isolated another rat cDNA containing a 123-amino acid insertion near the 5-prime end, which may represent an alternatively spliced form of the gene.
Hu et al. (1996) examined the pharmacologic profile of the Y5 receptor and found that it was unique from that of other NPY receptors and correlated well with peptides known to elicit feeding. By in situ hybridization, Gerald et al. (1996) localized rat brain Y5 expression to the paraventricular hypothalamic nucleus, the lateral hypothalamus, and other locations consistent with a role in the control of feeding behavior.
Gerald et al. (1996) suggested the possibility that Y1 (162641) and Y5 could map, in opposite orientation, to the same locus on human chromosome 4q. Hu et al. (1996) noted that the human Y5 receptor sequence is nearly identical to, but in the opposite orientation from, that of the human Y1 receptor sequence, overlapping the Y1 exon 1C promoter, exon 1C, and a portion of the associated intronic sequences. Herzog et al. (1997) pointed out that this finding confirms colocalization of the 2 genes at chromosome 4q31-q32, the known location of the NPYR1 gene. This unusual arrangement suggested to Herzog et al. (1997) that the 2 genes arose by a gene duplication event and that the 2 genes may be coordinately expressed.
Lutz et al. (1997) confirmed the assignment of NPY5R to chromosome 4 by Southern blot analysis of somatic cell hybrids. They mapped the Npy5r gene to mouse chromosome 8.
Ishihara et al. (2006) found that chronic administration of a Y5R antagonist selectively suppressed body weight gain and improved hyperinsulinemia in mice with diet-induced obesity. The antagonist did not affect the body weight of lean mice fed a regular diet or that of genetically obese leptin receptor (LEPR; 601007)-deficient mice or rats. Ishihara et al. (2006) concluded that Y5R is involved in regulation and development of diet-induced obesity.
Gerald, C., Walker, M. W, Criscione, L., Gustafson, E. L., Batzl-Hartmann, C., Smith, K. E., Vaysse, P., Durkin, M. M., Laz, T. M., Linemeyer, D. L., Schaffhauser, A. O., Whitebread, S., Hofbauer, K. G., Taber, R. I., Branchek, T. A., Weinshank, R. L. A receptor subtype involved in neuropeptide-Y-induced food intake. Nature 382: 168-171, 1996. [PubMed: 8700207] [Full Text: https://doi.org/10.1038/382168a0]
Herzog, H., Darby, K., Ball, H., Hort, Y., Beck-Sickinger, A., Shine, J. Overlapping gene structure of the human neuropeptide Y receptor subtypes Y1 and Y5 suggests coordinate transcriptional regulation. Genomics 41: 315-319, 1997. [PubMed: 9169127] [Full Text: https://doi.org/10.1006/geno.1997.4684]
Hu, Y., Bloomquist, B. T., Cornfield, L. J., DeCarr, L. B., Flores-Riveros, J. R., Friedman, L., Jiang, P., Lewis-Higgins, L., Sadlowski, Y., Schaefer, J., Velazquez, N., McCaleb, M. L. Identification of a novel hypothalamic neuropeptide Y receptor associated with feeding behavior. J. Biol. Chem. 271: 26315-26319, 1996. [PubMed: 8824284]
Ishihara, A., Kanatani, A., Mashiko, S., Tanaka, T., Hidaka, M., Gomori, A., Iwaasa, H., Murai, N., Egashira, S., Murai, T., Mitobe, Y., Matsushita, H., and 12 others. A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice. Proc. Nat. Acad. Sci. 103: 7154-7158, 2006. [PubMed: 16636293] [Full Text: https://doi.org/10.1073/pnas.0510320103]
Lutz, C. M., Richards, J. E., Scott, K. L., Sinha, S., Yang-Feng, T. L., Frankel, W. N., Thompson, D. A. Neuropeptide Y receptor genes mapped in human and mouse: receptors with high affinity for pancreatic polypeptide are not clustered with receptors specific for neuropeptide Y and peptide YY. Genomics 46: 287-290, 1997. [PubMed: 9417917] [Full Text: https://doi.org/10.1006/geno.1997.5024]