GPR173
Protein-coding gene in humans
From Wikipedia, the free encyclopedia
Probable G-protein coupled receptor 173 is a protein that in humans is encoded by the GPR173 gene.[5][6]
| GPR173 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | GPR173, SREB3, G protein-coupled receptor 173 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 300253; MGI: 1918021; HomoloGene: 10354; GeneCards: GPR173; OMA:GPR173 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Function
GPR173 (Also known as Super-Conserved Receptor Expressed in Brain 3, or SREB3) is a highly conserved G protein-coupled receptor (GPCR) that plays a significant role in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis, which is central to reproductive function.[7][8][9] It is expressed in the brain and ovaries, where it is considered the putative receptor for the peptide hormone phoenixin (PNX).
Activation of GPR173 by phoenixin potentiates the secretion of luteinizing hormone (LH) in response to gonadotropin-releasing hormone (GnRH), thereby promoting ovarian cycling and supporting reproductive processes.[8][9] Beyond reproduction, GPR173 has been implicated in diverse physiological functions such as food intake regulation, learning and memory, anxiety, inflammatory responses, and cardiac protection, largely through its modulation by phoenixin.[9]
Additionally, GPR173 may act as a receptor for cholecystokinin (CCK) in certain brain regions, mediating inhibitory synaptic plasticity and potentially serving as a therapeutic target for disorders involving excitation-inhibition imbalance.[10] The expression of GPR173 can be influenced by nutritional and environmental factors, indicating its role as a sensor and mediator in integrating external signals with neuroendocrine pathways.[7]
Ligands
GPR173 is an orphan class GPCR, however recent work has identified several compounds that may function as endogenous ligands.
Phoenixin
Recent studies have found GPR173 may act as a receptor for the peptides phoenixin-14 (PNX-14) and phoenixin-20 (PNX-20).[11][12][8] Both Phoenixins are alternate cleavage products of SMIM20.[11] PNX-20 treatments increased CREB phosphylation (pCREB) [13][14][15][16] and ERK1/2 phosphorylation (pERK1/2)[14] in various cell lines. These effects of PNX-20 were found to be dependent on GPR173 expression[14]. PNX-14 treatments were found to increase intracellular cAMP treatments under specific conditions within adipocytes [17]. As a ligand for GPR173, PNX-20 was found to have self regulatory behaviors by increasing GPR173 expression[16][15].
GnRH-(1-5)
GnRH-(1-5) is a degradation product of GnRH. GnRH-(1-5) was found to induce STAT3 phosphorylation (pSTAT3) in GN11 cells[18]. GnRH-(1-5) was not found to affect cAMP levels or IP1 levels in GN11 cells, and did not recruit Gα12 or Gα13 to GPR173 [19]. Activation of a G subunit associated pathway could not be confirmed, however GnRH-(1-5) treatments did have GPR173 recruit β-Arrestin 2 and PTEN[19]. GnRH-(1-5) induced production of pSTAT3 via GPR173 was found to be dependent on PTEN activity[19].
Cholecystokinin 8 (CCK8)
CCK8 has been found to interact with GPR173 in cell surface binding assays utilizing Flag-Tag assays[10]. CCK1R and CCK2R are established receptors for CCk8 that signal through Gαq/11. In GPR173+/+ CHO cells, CCK8 was found to mobilize [Ca2+]i with similar EC50 compared to CCK1R and CCK2R[10].
