GPR173

GPR173
Identifiers
Aliases	GPR173, SREB3, G protein-coupled receptor 173
External IDs	OMIM: 300253; MGI: 1918021; HomoloGene: 10354; GeneCards: GPR173; OMA:GPR173 - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xp11.22 Start 53,048,789 bp[1] End 53,080,615 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X F3 Start 151,126,594 bp[2] End 151,151,700 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence anterior pituitary right hemisphere of cerebellum ventricular zone tibial nerve right ovary left ovary right frontal lobe nucleus accumbens anterior cingulate cortex Top expressed in lumbar spinal ganglion trigeminal ganglion Rostral migratory stream ventricular zone autonomic nervous system ganglionic eminence sympathetic ganglion paravertebral ganglia midgut medial ganglionic eminence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signal transducer activity G protein-coupled receptor activity gonadotropin-releasing hormone receptor activity Cellular component integral component of membrane membrane plasma membrane Biological process G protein-coupled receptor signaling pathway negative regulation of neuron migration cellular response to gonadotropin-releasing hormone signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54328 70771 Ensembl ENSG00000184194 ENSMUSG00000056679 UniProt Q9NS66 Q6PI62 RefSeq (mRNA) NM_018969 NM_027543 NM_001313748 NM_001359449 NM_001359450 RefSeq (protein) NP_061842 NP_001300677 NP_081819 NP_001346378 NP_001346379 Location (UCSC) Chr X: 53.05 – 53.08 Mb Chr X: 151.13 – 151.15 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Probable G-protein coupled receptor 173 is a protein that in humans is encoded by the GPR173 gene.^[5][6]

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 Gα_q/11. In GPR173^+/+ CHO cells, CCK8 was found to mobilize [Ca²⁺]_i with similar EC₅₀ compared to CCK1R and CCK2R^[10].

See also

• SREB
• SMIM20

References

1. GRCh38: Ensembl release 89: ENSG00000184194 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000056679 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Matsumoto M, Saito T, Takasaki J, Kamohara M, Sugimoto T, Kobayashi M, et al. (Jul 2000). "An evolutionarily conserved G-protein coupled receptor family, SREB, expressed in the central nervous system". Biochemical and Biophysical Research Communications. 272 (2): 576–582. Bibcode:2000BBRC..272..576M. doi:10.1006/bbrc.2000.2829. PMID 10833454.
6. "Entrez Gene: GPR173 G protein-coupled receptor 173".
7. McIlwraith EK, Loganathan N, Belsham DD (April 2019). "Regulation of Gpr173 expression, a putative phoenixin receptor, by saturated fatty acid palmitate and endocrine-disrupting chemical bisphenol A through a p38-mediated mechanism in immortalized hypothalamic neurons". Molecular and Cellular Endocrinology. 485: 54–60. doi:10.1016/j.mce.2019.01.026. PMID 30716364.
8. Tullock CW, Mathews SK, Garcia-Galiano D, Elias CF, Samson WK, Yosten GL, et al. (September 2016). "Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 311 (3): R489–R496. doi:10.1152/ajpregu.00191.2016. ISSN 0363-6119. PMC 5142227. PMID 27440717.
9. Liang H, Zhao Q, Lv S, Ji X (2022). "Regulation and physiological functions of phoenixin". Frontiers in Molecular Biosciences. 9 956500. doi:10.3389/fmolb.2022.956500. PMC 9456248. PMID 36090042.
10. He L, Shi H, Zhang G, Peng Y, Ghosh A, Zhang M, et al. (March 2023). "A Novel CCK Receptor GPR173 Mediates Potentiation of GABAergic Inhibition". The Journal of Neuroscience. 43 (13): 2305–2325. doi:10.1523/JNEUROSCI.2035-22.2023. PMC 10072296. PMID 36813575.
11. Belsham DD, Mcilwraith EK (May 2018). "Phoenixin: uncovering its receptor, signaling and functions". Acta Pharmacologica Sinica. 39 (5): 774–778. doi:10.1038/aps.2018.13. ISSN 1745-7254. PMC 5943909. PMID 29671415.
12. Luo V, Belsham DD, Treen AK (2016-08-01). "Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the Novel Receptor GPR173". Molecular Endocrinology. 30 (8): 872–888. doi:10.1210/me.2016-1039. ISSN 0888-8809. PMC 5414621. PMID 27268078.
13. McIlwraith EK, Loganathan N, Belsham DD (2019-04-05). "Regulation of Gpr173 expression, a putative phoenixin receptor, by saturated fatty acid palmitate and endocrine-disrupting chemical bisphenol A through a p38-mediated mechanism in immortalized hypothalamic neurons". Molecular and Cellular Endocrinology. 485: 54–60. doi:10.1016/j.mce.2019.01.026. ISSN 0303-7207.
14. Treen AK, Luo V, Belsham DD (August 2016). "Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the Novel Receptor GPR173". Molecular Endocrinology (Baltimore, Md.). 30 (8): 872–888. doi:10.1210/me.2016-1039. ISSN 1944-9917. PMC 5414621. PMID 27268078.
15. Nguyen X, Nakamura T, Osuka S, Bayasula B, Nakanishi N, Kasahara Y, et al. (July 2019). "Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis". Reproduction. 158 (1): 25–34.
16. Yang Y, Lv Y, Liu J, Zhang S, Li Y, Shi Y (2020-04-01). "Phoenixin 20 promotes neuronal mitochondrial biogenesis via CREB–PGC-1α pathway". Journal of Molecular Histology. 51 (2): 173–181. doi:10.1007/s10735-020-09867-8. ISSN 1567-2387.
17. Billert M, Wojciechowicz T, Jasaszwili M, Szczepankiewicz D, Waśko J, Kaźmierczak S, et al. (2018-12-01). "Phoenixin-14 stimulates differentiation of 3T3-L1 preadipocytes via cAMP/Epac-dependent mechanism". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1863 (12): 1449–1457. doi:10.1016/j.bbalip.2018.09.006. ISSN 1388-1981.
18. Larco D, Cho-Clark M, Mani S, Wu TJ (1 February 2013). "The Metabolite GnRH-(1-5) Inhibits the Migration of Immortalized GnRH Neurons". Endocrinology. 154 (2). doi:10.1210/en.2012-1746. PMID 23321696.
19. Larco DO, Semsarzadeh NN, Cho-Clark M, Mani SK, Wu TJ (2013-12-01). "β-Arrestin 2 Is a Mediator of GnRH-(1–5) Signaling in Immortalized GnRH Neurons". Endocrinology. 154 (12): 4726–4736. doi:10.1210/en.2013-1286. ISSN 0013-7227. Archived from the original on 2023-11-14.