Relaxin/insulin-like family peptide receptor 1 explained

Relaxin/insulin-like family peptide receptor 1, also known as RXFP1, is a human G protein coupled receptor that is one of the relaxin receptors.^[1] It is a rhodopsin-like GPCR which is unusual in this class as it contains a large extracellular binding and signalling domain.^[2] Some reports suggest that RXFP1 forms homodimers,^{[3] [4]} however the most recent evidence indicates that relaxin binds a non-homodimer of RXFP1.^{[5] [6]}

See also

• Relaxin family peptide hormones
• Insulin/IGF/Relaxin family
• Relaxin
  • Relaxin-3

Further reading

• Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ . Receptors for relaxin family peptides . Annals of the New York Academy of Sciences . 1041 . 61–76 . May 2005 . 1 . 15956688 . 10.1196/annals.1282.010 . 2005NYASA1041...61B . 1185573 .
• Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ . International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides . Pharmacological Reviews . 58 . 1 . 7–31 . March 2006 . 16507880 . 10.1124/pr.58.1.9 . 7466039 .
• Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, van Duin M, Hsueh AJ . 6 . The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7 . Molecular Endocrinology . 14 . 8 . 1257–71 . August 2000 . 10935549 . 10.1210/me.14.8.1257 . free .
• Bartsch O, Bartlick B, Ivell R . Relaxin signalling links tyrosine phosphorylation to phosphodiesterase and adenylyl cyclase activity . Molecular Human Reproduction . 7 . 9 . 799–809 . September 2001 . 11517286 . 10.1093/molehr/7.9.799 . free .
• Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ . Activation of orphan receptors by the hormone relaxin . Science . 295 . 5555 . 671–4 . January 2002 . 11809971 . 10.1126/science.1065654 . 2002Sci...295..671H . 32693420 .
• Sudo S, Kumagai J, Nishi S, Layfield S, Ferraro T, Bathgate RA, Hsueh AJ . H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2 . The Journal of Biological Chemistry . 278 . 10 . 7855–62 . March 2003 . 12506116 . 10.1074/jbc.M212457200 . free .
• Ivell R, Balvers M, Pohnke Y, Telgmann R, Bartsch O, Milde-Langosch K, Bamberger AM, Einspanier A . 6 . Immunoexpression of the relaxin receptor LGR7 in breast and uterine tissues of humans and primates . Reproductive Biology and Endocrinology . 1 . 114 . November 2003 . 14633277 . 293425 . 10.1186/1477-7827-1-114 . free .
• Luna JJ, Riesewijk A, Horcajadas JA, Van Os RD, Domínguez F, Mosselman S, Pellicer A, Simón C . 6 . Gene expression pattern and immunoreactive protein localization of LGR7 receptor in human endometrium throughout the menstrual cycle . Molecular Human Reproduction . 10 . 2 . 85–90 . February 2004 . 14742692 . 10.1093/molehr/gah019 . free .
• Bond CP, Parry LJ, Samuel CS, Gehring HM, Lederman FL, Rogers PA, Summers RJ . Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle . The Journal of Clinical Endocrinology and Metabolism . 89 . 7 . 3477–85 . July 2004 . 15240635 . 10.1210/jc.2003-030798 . free .
• Liu C, Chen J, Kuei C, Sutton S, Nepomuceno D, Bonaventure P, Lovenberg TW . Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7 . Molecular Pharmacology . 67 . 1 . 231–40 . January 2005 . 15465925 . 10.1124/mol.104.006700 . 25164369 .
• Scott DJ, Layfield S, Riesewijk A, Morita H, Tregear GW, Bathgate RA . Identification and characterization of the mouse and rat relaxin receptors as the novel orthologues of human leucine-rich repeat-containing G-protein-coupled receptor 7 . Clinical and Experimental Pharmacology & Physiology . 31 . 11 . 828–32 . November 2004 . 15566402 . 10.1111/j.1440-1681.2004.04075.x . 22463239 .
• Büllesbach EE, Schwabe C . The trap-like relaxin-binding site of the leucine-rich G-protein-coupled receptor 7 . The Journal of Biological Chemistry . 280 . 14 . 14051–6 . April 2005 . 15695505 . 10.1074/jbc.M500030200 . free .
• Tang M, Mazella J, Zhu HH, Tseng L . Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells . Molecular Human Reproduction . 11 . 4 . 237–43 . April 2005 . 15722441 . 10.1093/molehr/gah149 . free .
• Hopkins EJ, Bathgate RA, Gooley PR . The human LGR7 low-density lipoprotein class A module requires calcium for structure . Annals of the New York Academy of Sciences . 1041 . 27–34 . May 2005 . 1 . 15956684 . 10.1196/annals.1282.006 . 2005NYASA1041...27H . 12876694 .
• Bond CP, Parry LJ, Samuel CS, Gehring HM, Lederman FL, Rogers PA, Summers RJ . Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle . Annals of the New York Academy of Sciences . 1041 . 136–43 . May 2005 . 1 . 15956698 . 10.1196/annals.1282.020 . 2005NYASA1041..136B . 38242216 .
• Halls ML, Bathgate RA, Summers RJ . Signal switching after stimulation of LGR7 receptors by human relaxin 2 . Annals of the New York Academy of Sciences . 1041 . 288–91 . May 2005 . 1 . 15956719 . 10.1196/annals.1282.042 . 2005NYASA1041..288H . 42606513 .
• Muda M, He C, Martini PG, Ferraro T, Layfield S, Taylor D, Chevrier C, Schweickhardt R, Kelton C, Ryan PL, Bathgate RA . 6 . Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity . Molecular Human Reproduction . 11 . 8 . 591–600 . August 2005 . 16051677 . 10.1093/molehr/gah205 . free .

External links

• Web site: Relaxin Family Peptide Receptors: RXFP1 . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-09 . 2016-03-03 . https://web.archive.org/web/20160303185216/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3022 . dead .

Notes and References

1. Web site: Entrez Gene: RXFP1 relaxin/insulin-like family peptide receptor 1.
2. Sethi A, Bruell S, Patil N, Hossain MA, Scott DJ, Petrie EJ, Bathgate RA, Gooley PR . 6 . The complex binding mode of the peptide hormone H2 relaxin to its receptor RXFP1 . Nature Communications . 7 . 1 . 11344 . April 2016 . 27088579 . 10.1038/ncomms11344 . 4837482 . free . 2016NatCo...711344S .
3. Svendsen AM, Zalesko A, Kønig J, Vrecl M, Heding A, Kristensen JB, Wade JD, Bathgate RA, De Meyts P, Nøhr J . 6 . Negative cooperativity in H2 relaxin binding to a dimeric relaxin family peptide receptor 1 . Molecular and Cellular Endocrinology . 296 . 1–2 . 10–7 . December 2008 . 18723073 . 10.1016/j.mce.2008.07.014 . 32739782 .
4. Kern A, Hubbard D, Amano A, Bryant-Greenwood GD . Cloning, expression, and functional characterization of relaxin receptor (leucine-rich repeat-containing g protein-coupled receptor 7) splice variants from human fetal membranes . Endocrinology . 149 . 3 . 1277–94 . March 2008 . 18079195 . 2275365 . 10.1210/en.2007-1348 .
5. Hoare BL, Bruell S, Sethi A, Gooley PR, Lew MJ, Hossain MA, Inoue A, Scott DJ, Bathgate RA . 6 . Multi-Component Mechanism of H2 Relaxin Binding to RXFP1 through NanoBRET Kinetic Analysis . English . iScience . 11 . 93–113 . January 2019 . 30594862 . 6309025 . 10.1016/j.isci.2018.12.004 . 2019iSci...11...93H .
6. Hoare BL, Kocan M, Bruell S, Scott DJ, Bathgate RA . Using the novel HiBiT tag to label cell surface relaxin receptors for BRET proximity analysis . Pharmacology Research & Perspectives . 7 . 4 . e00513 . August 2019 . 31384473 . 6667744 . 10.1002/prp2.513 .