GPR133

ADGRD1
Identifiers
Aliases	ADGRD1, PGR25, GPR133, adhesion G protein-coupled receptor D1
External IDs	OMIM: 613639; MGI: 3041203; HomoloGene: 34616; GeneCards: ADGRD1; OMA:ADGRD1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.33 Start 130,953,907 bp[1] End 131,141,469 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 G1.3 Start 129,173,814 bp[2] End 129,281,663 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cardiac muscle tissue of right atrium right auricle of heart tibial nerve decidua right lung sural nerve upper lobe of left lung myocardium of left ventricle gastric mucosa apex of heart Top expressed in lumbar spinal ganglion Ileal epithelium lactiferous gland ankle joint extraocular muscle white adipose tissue body of femur sciatic nerve ascending aorta thoracic diaphragm More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled receptor activity transmembrane signaling receptor activity signal transducer activity Cellular component integral component of membrane plasma membrane membrane intracellular anatomical structure integral component of plasma membrane Biological process G protein-coupled receptor signaling pathway cell surface receptor signaling pathway signal transduction adenylate cyclase-activating G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 283383 243277 Ensembl ENSG00000111452 ENSMUSG00000044017 UniProt Q6QNK2 Q80T32 RefSeq (mRNA) NM_198827 NM_001330497 NM_001081342 NM_177734 NM_001347486 RefSeq (protein) NP_001317426 NP_942122 NP_001074811 NP_001334415 Location (UCSC) Chr 12: 130.95 – 131.14 Mb Chr 5: 129.17 – 129.28 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Probable G-protein coupled receptor 133 is a protein that in humans is encoded by the GPR133 gene.^[5][6]

This gene encodes a member of the adhesion-GPCR family of receptors. Family members are characterized by an extended extracellular region with a variable number of protein domains coupled to a TM7 domain via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.^[7][8]

GPR133 binds androgens, specifically the androgen 5α-dihydrotestosterone (5α-DHT).^[9] GPR133 is an adhesion G protein-coupled receptor that functions as a membrane receptor for androgens. When activated by 5α-DHT, GPR133 increases intracellular cyclic AMP (cAMP) levels in muscle cells, leading to enhanced muscle strength.^[9]

Agonists of GPR133 such as GL64 and AP503 have potential applications in the treatment of osteoporosis.^[10][11]

References

1. GRCh38: Ensembl release 89: ENSG00000111452 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000044017 – 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. "Entrez Gene: GPR133 G protein-coupled receptor 133".
6. Fredriksson R, Lagerström MC, Höglund PJ, Schiöth HB (November 2002). "Novel human G protein-coupled receptors with long N-terminals containing GPS domains and Ser/Thr-rich regions". FEBS Letters. 531 (3): 407–414. doi:10.1016/S0014-5793(02)03574-3. PMID 12435584. S2CID 7449692.
7. Stacey M, Yona S (2011). AdhesionGPCRs: Structure to Function (Advances in Experimental Medicine and Biology). Berlin: Springer. ISBN 978-1-4419-7912-4.
8. Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, Brunger AT (March 2012). "A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis". The EMBO Journal. 31 (6): 1364–1378. doi:10.1038/emboj.2012.26. PMC 3321182. PMID 22333914.
9. Yang Z, Ping YQ, Wang MW, Zhang C, Zhou SH, Xi YT, et al. (January 2025). "Identification, structure, and agonist design of an androgen membrane receptor". Cell. doi:10.1016/j.cell.2025.01.006. PMID 39884271.
10. He L, Zhang Q, You Y, Sun P, Xu Z, Li R, Wang F, Zhang S, He J, Shen J, Zhao L, Hong Y, Li Y, Liu M, Sun JP, Wang N, Sun Y, Yang H, Luo J. Exogenous activation of the adhesion GPCR ADGRD1/GPR133 protects against bone loss by negatively regulating osteoclastogenesis. Sci Adv. 2025 Jul 11;11(28):eads3829. doi:10.1126/sciadv.ads3829 PMID 40644539
11. Lehmann J, Lin H, Zhang Z, Wiermann M, Ricken AM, Brinkmann F, Brendler J, Ullmann C, Bayer L, Berndt S, Penk A, Winkler N, Hirsch FW, Fuhs T, Käs J, Xiao P, Schöneberg T, Rauner M, Sun JP, Liebscher I. The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation. Signal Transduct Target Ther. 2025 Jun 30;10(1):199. doi:10.1038/s41392-025-02291-y PMID 40583059

Further reading

• Vanti WB, Nguyen T, Cheng R, Lynch KR, George SR, O'Dowd BF (May 2003). "Novel human G-protein-coupled receptors". Biochemical and Biophysical Research Communications. 305 (1): 67–71. doi:10.1016/S0006-291X(03)00709-5. PMID 12732197.
• Bjarnadóttir TK, Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB (July 2004). "The human and mouse repertoire of the adhesion family of G-protein-coupled receptors". Genomics. 84 (1): 23–33. doi:10.1016/j.ygeno.2003.12.004. PMID 15203201.