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Hsueh lab

HPMR

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since 01/2001:
176557

OKDB#: 1401
 Symbols: Species: human
 Synonyms:  Locus:
HPMR


For retrieval of Nucleotide and Amino Acid sequences please go to: Entrez Gene
Mammalian Reproductive Genetics   Endometrium Database Resource   Orthologous Genes

R-L INTERACTIONS   MGI

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General Comment G protein-coupled receptors (GPCRs) are a large family of receptors that have a similar structure characterized by 7 transmembrane domains.SREB3 is an orphan receptor. This is an orphan receptor./////Identification and molecular docking studies for novel inverse agonists of SREB, super conserved receptor expressed in brain. Yanai T et al. (2017) The identification of novel synthetic ligands for G protein-coupled receptors (GPCRs) is important not only for understanding human physiology, but also for the development of novel drugs, especially for orphan GPCRs for which endogenous ligands are unknown. One of the orphan GPCR subfamilies, Super conserved Receptor Expressed in Brain (SREB), consists of GPR27, GPR85 and GPR173 and is expressed in the central nervous system. We report herein the identification of inverse agonists for the SREB family without their agonists. We carried out an in vitro screening of 5472 chemical compounds from the RIKEN NPDepo chemical library. The binding of [(35) S]GTPγS to the GPR173-Gsα fusion protein expressed in Sf9 cells was measured and resulted in the identification of 8 novel GPR173 inverse agonists. The most potent compound showed an IC50 of approximately 8 μm. The identified compounds were also antagonists for other SREB members, GPR27 and GPR85. These results indicated that the SREB family could couple Gs-type G proteins, and SREB-Gsα fusion proteins showed significant constitutive activities. Moreover, a molecular model of GPR173 was constructed using the screening results. The combination of computational and biological methods will provide a unique approach to ligand identification for orphan GPCRs and brain research.//////////////////

General function Receptor
Comment
Cellular localization Plasma membrane
Comment
Ovarian function Primary follicle growth, Steroid metabolism
Comment Effect of the Neuropeptide Phoenixin and Its Receptor GPR173 During Folliculogenesis. Nguyen XP et al. (2019) Folliculogenesis is a complex process, defined by the growth and development of follicles from the primordial population. Granulosa cells (GCs) play a vital role in every stage of follicular growth through proliferation, acquisition of gonadotropic responsiveness, steroidogenesis, and production of autocrine/paracrine factors. A recently discovered hypothalamic neuropeptide phoenixin, is involved in the regulation of the reproductive system. Phoenixin acts through its receptor, G protein-coupled receptor 173 (GPR173), to activate the cAMP/PKA pathway leading to the phosphorylation of CREB (pCREB). Here, we demonstrated the expression patterns of phoenixin and GPR173 in human ovary and explored its role in folliculogenesis. Phoenixin and GPR173 were both expressed in the human ovarian follicle, with increased expression in GCs as the follicle grows. Phoenixin treatment at 100 nM for 24 h induced the proliferation of human non-luteinized granulosa cell line, HGrC1 and significantly increased the expression levels of CYP19A1, FSHR, LHR, and KITL, but decreased NPPC expression levels. These effects were suppressed by GPR173 siRNA. The expression level of CREB1, pCREB, and estradiol (E2) production in the culture medium was significantly enhanced by phoenixin treatment in a concentration-dependent manner. Phoenixin also significantly increased the follicular area in a murine ovarian tissue culture model, leading to an increased number of ovulated oocytes with a higher level of maturation. Taken together, our data demonstrate that phoenixin is an intraovarian factor that promotes follicular growth through its receptor GPR173 by accelerating proliferation of GCs, inducing E2 production, and increasing the expression of genes related to follicle development.//////////////////
Expression regulated by
Comment
Ovarian localization Granulosa
Comment Levels of the neuropeptide phoenixin-14 and its receptor GRP173 in the hypothalamus, ovary and periovarian adipose tissue in rat model of polycystic ovary syndrome. Kalamon N et al. (2020) Phoenixin (PNX) is a newly discovered peptide produced by proteolytic cleavage of a small integral membrane protein 20 (Smim20), which acts as an important regulator of energy homeostasis and reproduction. Since dysfunction of reproduction is characteristic in polycystic ovarian syndrome (PCOS), the role of PNX in pathogenesis of PCOS needs further investigation. The objective of this study was to determine expression of Smim20, PNX-14 and its receptor GRP173 in the hypothalamus, ovary and periovarian adipose tissue (PAT) of letrozole induced PCOS rats. Phosphorylation of extracellular signal-regulated kinase (ERK1/2), protein kinases A (PKA) and B (Akt) were also estimated. We observed that PCOS rats had high weight gain and a number of ovarian cyst, high levels of testosterone, luteinizing hormone and PNX-14, while low estradiol. Smim20 mRNA expression was higher in the ovary and PAT, while PNX-14 peptide production was higher only in the ovary of PCOS rat. Moreover, in PCOS rats Gpr173 level was lower in PAT but at the protein level increased only in the ovary. Depending on the tissues, kinases phosphorylation were significantly differ in PCOS rats. Our results showed higher levels of PNX-14 in PCOS rats and indicated some novel findings regarding the mechanisms of PCOS pathophysiology.////////////////// Matsumoto et al 2000 reported that high levels of SREB3 expression were found in brain and ovary, and lower levels in small intestine. Within brain, SREB3 expression was found in all regions tested, with the highest levels in the cerebellum and cerebral cortex.
Follicle stages
Comment
Phenotypes
Mutations 0 mutations
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Phenotypes and GWAS show phenotypes and GWAS
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created: Jan. 16, 2002, 8:52 p.m. by: hsueh   email:
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last update: June 10, 2020, 11:48 a.m. by: hsueh    email:



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