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GPR156

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GPR156
Identifiers
AliasesGPR156, GABABL, PGR28, G protein-coupled receptor 156
External IDsOMIM: 610464; MGI: 2653880; HomoloGene: 17683; GeneCards: GPR156; OMA:GPR156 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001168271
NM_153002

NM_153394

RefSeq (protein)

NP_001161743
NP_694547

NP_700443

Location (UCSC)Chr 3: 120.16 – 120.29 MbChr 16: 37.74 – 37.83 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

GPR156 (G protein-coupled receptor 156), is a human gene which encodes a G protein-coupled receptor belonging to metabotropic glutamate receptor subfamily.[5] By sequence homology, this gene was proposed as being a possible GABAB receptor subunit, however when expressed in cells alone or with other GABAB subunits, no response to GABAB ligands could be detected. In vitro studies on GPR156 constitutive activity revealed a high level of basal activation and coupling with members of the Gi/Go heterotrimeric G protein family.[6] In 2021, an article was reported that GPR156 modulates hair cell orientation in the cochlea.[7] Also, it was proposed that GPR156 is related to congenital hearing loss.[8] GPR156 in complex with any of the Gi/o heterotrimers regulates the hair cell orientation.[9] In 2024, molecular structures of G-free and Go-bound GPR156 were characterized by using cryogenic electron microscopy.[10]

Structure

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Among class C GPCR family members, GPR156 is unique because it lacks a large extracellular domain. Structural analyses revealed that the asymmetric binding of Go-protein to GPR156 triggers conformational change of its cytoplasmic face without altering dimer interface.[10]  Although the inactive class C GPCRs undergo rearrangement of their dimeric interface, the agonist- and/or the positive allosteric modulator-bound class C GPCRs retain their dimeric interface upon G-protein binding. Thus, the G-free GPR156 is likely to represent an active state.[10] Structural and functional analyses suggest that abundant endogenous phospholipids, receptor dimerization, and the G-protein binding-induced conformational change of the cytoplasmic face are the primary reasons for constitutive activation of GPR156.[10] Phosphatidylglycerol further stimulates the activity of GPR156, which suggests the environmental changes of the phospholipid composition may regulate the GPR156 activity.[10]

G-bound GPR156 (PDB: 8IED)
G-free GPR156 (PDB: 8IEI)

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000175697Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046961Ensembl, 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. ^ "Entrez Gene: GPR156 G protein-coupled receptor 156".
  6. ^ Watkins LR, Orlandi C (August 2021). "In vitro profiling of orphan G protein coupled receptor (GPCR) constitutive activity". British Journal of Pharmacology. 178 (15): 2963–2975. doi:10.1111/bph.15468. PMID 33784795. S2CID 232430996.
  7. ^ Kindt KS, Akturk A, Jarysta A, Day M, Beirl A, Flonard M, et al. (May 2021). "EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia". Nature Communications. 12 (1): 2861. Bibcode:2021NatCo..12.2861K. doi:10.1038/s41467-021-22997-1. PMC 8129141. PMID 34001891.
  8. ^ Ramzan M, Bozan N, Seyhan S, Zafeer MF, Ayral A, Duman D, et al. (October 2023). "Novel GPR156 variants confirm its role in moderate sensorineural hearing loss". Scientific Reports. 13 (1): 17010. Bibcode:2023NatSR..1317010R. doi:10.1038/s41598-023-44259-4. PMC 10562426. PMID 37814107.
  9. ^ Jarysta A, Tadenev AL, Day M, Krawchuk B, Low BE, Wiles MV, et al. (April 2024). "Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis". eLife. 12. doi:10.7554/eLife.88186.1. PMID 38651641.
  10. ^ a b c d e Shin J, Park J, Jeong J, Lam JH, Qiu X, Wu D, et al. (April 2024). "Constitutive activation mechanism of a class C GPCR". Nature Structural & Molecular Biology. 31 (4): 678–687. doi:10.1038/s41863-024-01224-7. PMID 38332368.

Further reading

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