Alternative titles; symbols
HGNC Approved Gene Symbol: NPY4R
Cytogenetic location: 10q11.22 Genomic coordinates (GRCh38): 10:46,461,099-46,470,668 (from NCBI)
Pancreatic polypeptide (PP; 167780), neuropeptide Y (NPY; 162640), and peptide YY (PYY; 600781) are related 36-amino acid hormones. A number of structurally related receptors for these peptides have been isolated (e.g., NPY2R; 162642). Bard et al. (1995) used the rat Y1 receptor (NPY1R; 162641) as a probe to clone a novel receptor, PPYR1 (termed Y4 by them), from a human genomic DNA library. PPYR1 encodes a predicted 375-amino acid polypeptide having highest homology to the Y1 receptor gene (42% amino acid identity). Using RT-PCR, they showed that the PPYR1 receptor is expressed in several human tissues, including brain, coronary artery, and ileum.
Bard et al. (1995) expressed the PPYR1 gene in COS-7 cells and performed a hormone-binding assay which showed that the PPYR1 receptor binds (from highest to lowest affinity) PP, PYY, and NPY hormones.
Bard et al. (1995) determined that the PPYR1 gene is intronless.
By fluorescence in situ hybridization, Darby et al. (1997) mapped the PPYR1 gene to human 10q11.2; by interspecific backcross mapping, they assigned the gene to mouse chromosome 14.
The genes encoding NPY1R and NPY2R have been mapped to 4q31.3-q32 and 4q31, respectively. They are located approximately 6 cM apart and have been mapped to conserved syntenic linkage groups on mouse chromosome 8 and 3, respectively. The human type 5 receptor (NPY5R; 602001) is also thought to be located on 4q31-q32; part of its sequence is nearly identical to, but in the opposite orientation from, that of the Y1 receptor sequence. To determine whether all functional human NPY receptor genes are clustered on chromosome 4, Lutz et al. (1997) mapped PPYR1 and NPY5R using somatic cell hybrids. They found that PPYR1 maps to chromosome 10. For regionalization, they used mapping to a YAC library using PCR and the primers for the PPYR1 gene. Their findings suggested that 10q11.2-q21.2 is the likely cytogenetic location of PPYR1. Lutz et al. (1997) mapped the Ppyr1 gene to mouse chromosome 14, approximately 15 cM from the centromere.
Sainsbury et al. (2002) developed Y4-null mice. Male null mice showed aggressive behavior. Female mice behaved normally in early life and adulthood, but became aggressive after 20 to 24 weeks of age. Null animals also showed reduced body weight and increased plasma pancreatic polypeptide levels. When the Y4-null mutation was introduced on the ob/ob (164160) genetic background, the Y4 mutation improved the fertility of the ob/ob mice. There was increased gonadotropin-releasing hormone expression and enhanced mammary gland development. The Y4-null mutation did not, however, reduce body weight or excessive adiposity of ob/ob mice.
Bard, J. A., Walker, M. W., Branchek, T. A., Weinshank, R. L. Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY J. Biol. Chem 270: 26762-26765, 1995. [PubMed: 7592911] [Full Text: https://doi.org/10.1074/jbc.270.45.26762]
Darby, K., Eyre, H. J., Lapsys, N., Copeland, N. G., Gilbert, D. J., Couzens, M., Antonova, O., Sutherland, G. R., Jenkins, N. A., Herzog, H. Assignment of the Y-4 receptor gene (PPYR1) to human chromosome 10q11.2 and mouse chromosome 14. Genomics 46: 513-515, 1997. [PubMed: 9441761] [Full Text: https://doi.org/10.1006/geno.1997.5071]
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]
Sainsbury, A., Schwarzer, C., Couzens, M., Jenkins, A., Oakes, S. R., Ormandy, C. J., Herzog, H. Y4 receptor knockout rescues fertility in ob/ob mice. Genes Dev. 16: 1077-1088, 2002. [PubMed: 12000791] [Full Text: https://doi.org/10.1101/gad.979102]