Assignment of the Y4Receptor Gene (PPYR1) to Human Chromosome 10q11.2 and Mouse Chromosome 14

doi:10.1006/geno.1997.5071

Genomics

Volume 46, Issue 3, 15 December 1997, Pages 513-515

https://doi.org/10.1006/geno.1997.5071 Get rights and content

Abstract

The human and mouse genes for the neuropeptide Y₄receptor have been isolated, sequenced, and shown to contain no introns within the coding region of the gene. Nonisotopicin situhybridization and interspecific mouse backcross mapping have localized the genes to human chromosome 10q11.2 and mouse chromosome 14. Five nucleotide variants, which do not alter the protein sequence, have been identified within the coding region of the human receptor gene. The human Y₄subtype is most closely related to the Y₁-receptor subtype (42%), suggesting that it evolved from an ancestral Y₁-like receptor via an RNA-mediated transpositional event.

References (13)

D.A. Ammar et al.
Characterization of the human type 2 neuropeptide Y receptor gene (NPY2R) and localization to the chromosome 4q region containing the type 1 neuropeptide Y receptor gene
Genomics
(1996)
J.A. Bard et al.
Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY
J. Biol. Chem.
(1995)
A. Blomqvist et al.
Y-receptor subtypes—How many more?
Trends Neurosci.
(1997)
N.G. Copeland et al.
Development and applications of a molecular genetic linkage map of the mouse genome
Trends Genet.
(1991)
P. Gregor et al.
Cloning and characterisation of a novel receptor to pancreatic polypeptide, a member of the neuropeptide Y receptor family
FEBS Lett.
(1996)
H. Herzog et al.
Genomic organisation, localisation, and allelic differences in the gene for the human neuropeptide Y Y1 receptor
J. Biol. Chem.
(1993)

There are more references available in the full text version of this article.

Cited by (11)

Illuminating the neuropeptide Y<inf>4</inf> receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective
2024, Neuropeptides
The neuropeptide Y₄ receptor (Y₄R), a rhodopsin-like G protein-coupled receptor (GPCR) and the hormone pancreatic polypeptide (PP) are members of the neuropeptide Y family consisting of four receptors (Y₁R, Y₂R, Y₄R, Y₅R) and three highly homologous peptide ligands (neuropeptide Y, peptide YY, PP). In this family, the Y₄R is of particular interest as it is the only subtype with high affinity to PP over NPY. The Y₄R, as a mediator of PP signaling, has a pivotal role in appetite regulation and energy homeostasis, offering potential avenues for the treatment of metabolic disorders such as obesity. PP as anorexigenic peptide is released postprandial from the pancreas in response to food intake, induces satiety signals and contributes to hamper excessive food intake. Moreover, this system was also described to be associated with different types of cancer: overexpression of Y₄R have been found in human adenocarcinoma cells, while elevated levels of PP are related to the development of pancreatic endocrine tumors. The pharmacological relevance of the Y₄R advanced the search for potent and selective ligands for this receptor subtype, which will be significantly progressed through the elucidation of the active state PP-Y₄R cryo-EM structure. This review summarizes the development of novel PP-derived ligands, like Obinepitide as dual Y₂R/Y₄R agonist in clinical trials or UR-AK86c as small hexapeptide agonist with picomolar affinity, as well as the first allosteric modulators that selectively target the Y₄R, e.g. VU0506013 as potent Y₄R positive allosteric modulator or (S)-VU0637120 as allosteric antagonist. Here, we provide valuable insights into the complex physiological functions of the Y₄R and PP and the pharmacological relevance of the system in appetite regulation to open up new avenues for the development of tool compounds for targeted therapies with potential applications in metabolic disorders.
Neuropeptide Y and Bone Regulation
2013, Genetics of Bone Biology and Skeletal Disease
Neuropeptide Y and Bone Formation
2013, Translational Endocrinology of Bone
Neuropeptide Y and Bone Formation
2012, Translational Endocrinology of Bone: Reproduction, Metabolism, and the Central Nervous System
Molecular analysis of the neuropeptide Y1 receptor gene in human idiopathic gonadotropin-dependent precocious puberty and isolated hypogonadotropic hypogonadism
2007, Fertility and Sterility
Citation Excerpt :
Furthermore, in our current study, we identified only 1 nucleotide substitution out of 210 alleles that were sequenced. The genes encoding the NPY-Y1R and NPY-Y5R receptor subtypes are transcribed in opposite directions from a common promoter in a region of chromosome 4q31-32 and most likely evolved from a gene duplication event (28). Thus, a mutation in one of these receptors genes may have consequences on expression of the other gene.
To investigate the role of mutations or polymorphisms in the NPY-Y1R gene in human idiopathic central pubertal disorders.
Molecular studies.
University hospital.
Thirty-three patients with gonadotropin-dependent precocious puberty, 22 with hypogonadotropic hypogonadism, and 50 controls.
Genomic DNA extraction, NPY-Y1R gene sequence analysis, cell-surface expression, and functional activity of an identified receptor variant.
Results of sequencing, cell-surface receptor expression, and receptor function.
A heterozygous substitution of lysine (K) by threonine (T) at position 374 in the carboxyl terminal region of NPY-Y1R was identified in a girl with familial GDPP. Her mother, who had pubertal developmental at appropriate age, carried the same genetic variant. Introduction of the K374T variant into an expression vector containing the human NPY-Y1R complementary DNA led to a partial reduction in cell-surface expression of NPY-Y1R in transiently transfected HEK293 cells. This mutation did not lead to a significant reduction in NPY-stimulated activity of the receptor in this heterologous expression system. No other allelic variants of the NPY-Y1R gene were identified in patients or controls.
We have identified an inherited heterozygous variant of the NPY-Y1R gene in a girl with precocious puberty; however, this most likely did not contribute to her phenotype. Mutations of the highly conserved NPY-Y1R gene do not appear to represent a frequent mechanism underlying human idiopathic central pubertal disorders.
Introduction to the reviews on neuropeptide Y
2004, Neuropeptides
Neuropeptide Y (NPY) was first reported as an abundant peptide in brain tissue in 1982. Shortly thereafter, NPY was found to be a member of a peptide family consisting of the endocrine peptides pancreatic polypeptide (PP) and peptide YY (PYY). These peptides exert most of their biological effects through five G-protein coupled receptors termed Y1, Y2, Y4, Y5 and y6 that mediate either inhibition adenylate cyclase or increases in intracellular calcium. Since the discovery of NPY, a robust a body of literature has developed around the potential functions of this peptide. While initial findings identified NPY is an important contributor to the regulation of feeding, body weight and blood pressure, more recent work as revealed more subtle functions of this peptide and its potential role in affective disorders, bone formation and cravings. The accompanying twelve reviews detail important developments in our understanding of the functional role of NPY.

View all citing articles on Scopus

¹: To whom correspondence should be addressed at Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst NSW 2010, Sydney, Australia. Telephone: 61 2 9295 8296. Fax: 61 2 9295 8281. E-mail: [email protected].

View full text

SHORT COMMUNICATIONAssignment of the Y4Receptor Gene (PPYR1) to Human Chromosome 10q11.2 and Mouse Chromosome 14

Abstract

Genomics

J. Biol. Chem.

Trends Neurosci.

Trends Genet.

FEBS Lett.

J. Biol. Chem.

SHORT COMMUNICATION
Assignment of the Y₄Receptor Gene (PPYR1) to Human Chromosome 10q11.2 and Mouse Chromosome 14