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Gene Review

RXFP1  -  relaxin/insulin-like family peptide...

Homo sapiens

Synonyms: LGR7, Leucine-rich repeat-containing G-protein coupled receptor 7, RXFPR1, Relaxin family peptide receptor 1, Relaxin receptor 1
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Disease relevance of RXFP1


High impact information on RXFP1

  • Furthermore, we demonstrate via structural studies on mutated LDLa modules and functional studies on mutated full-length receptors that a hydrophobic surface within the N-terminal region of the module is essential for activation of RXFP1 receptor signal in response to relaxin stimulation [3].
  • Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility [4].
  • Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells [4].
  • This study highlights the essential role of the LDLa module in LGR7 and LGR8 function and introduces a novel model of GPCR regulation [5].
  • We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs [6].

Biological context of RXFP1

  • RXFP1 and RXFP2 have at least two binding sites - a high-affinity site in the leucine-rich repeat region of the ectodomain and a lower-affinity site in an exoloop of the transmembrane region [1].
  • Eight reporter genes were tested at both receptors as a screen to identify other signaling pathways activated by RXFP1 and RXFP2 [7].
  • Comparisons between RXFP1, RXFP2, the chimeric receptors, and the truncated receptors revealed that the interaction between receptor sites is critical for optimal ligand binding and signal transduction and that the ectodomain is essential for signaling [8].
  • In contrast, LGR7.2, LGR7.10 and LGR 8.1 all contain an intact seven transmembrane domain and most of the extracellular region, lacking only one or two exons in the ectodomain [9].
  • Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle [10].

Anatomical context of RXFP1


Associations of RXFP1 with chemical compounds

  • The NMR Solution Structure of the Relaxin (RXFP1) Receptor Lipoprotein Receptor Class A Module and Identification of Key Residues in the N-terminal Region of the Module That Mediate Receptor Activation [3].
  • Activation of RXFP1 or RXFP2 causes increased cAMP and the initial response for both receptors is the resultant of Gs-mediated activation and G(oB)-mediated inhibition of adenylate cyclase [1].
  • Adenylyl cyclase activation by relaxin in purified plasma membranes from THP-1 cells was not inhibited by LY294002, consistent with a mechanism involving direct stimulation by a Galphas-coupled relaxin receptor [14].
  • Phylogenetic analysis showed that there are three LGR subgroups: the known glycoprotein hormone receptors; LGR4 to 6; and a third subgroup represented by LGR7 [15].
  • Demonstration of a relaxin receptor and relaxin-stimulated tyrosine phosphorylation in human lower uterine segment fibroblasts [16].
  • The mutation of the putative N-linked glycosylation site (Asn(36)) decreased cAMP production and reduced cell surface expression to 37% of the wild-type LGR7 [17].
  • In coexpression studies, each splice variant interacted directly with the WT-LGR7 and exerted a dominant-negative effect on cAMP accumulation by the WT-LGR7 after relaxin treatment [18].

Physical interactions of RXFP1


Regulatory relationships of RXFP1

  • H3 relaxin was also able to activate native LGR7 receptors [11].
  • There is also evidence that RXFP1 can activate Erk1/2 and nitric oxide synthase, and relaxin has been reported to enter cells and activate glucocorticoid receptors [20].
  • Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism [6].

Other interactions of RXFP1


Analytical, diagnostic and therapeutic context of RXFP1


  1. Relaxin Family Peptide Receptors - former orphans reunite with their parent ligands to activate multiple signalling pathways. Halls, M.L., van der Westhuizen, E.T., Bathgate, R.A., Summers, R.J. Br. J. Pharmacol. (2007) [Pubmed]
  2. Genetic targeting of relaxin and insl3 signaling in mice. Feng, S., Bogatcheva, N.V., Kamat, A.A., Agoulnik, A.I. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  3. The NMR Solution Structure of the Relaxin (RXFP1) Receptor Lipoprotein Receptor Class A Module and Identification of Key Residues in the N-terminal Region of the Module That Mediate Receptor Activation. Hopkins, E.J., Layfield, S., Ferraro, T., Bathgate, R.A., Gooley, P.R. J. Biol. Chem. (2007) [Pubmed]
  4. Relaxin enhances the oncogenic potential of human thyroid carcinoma cells. Hombach-Klonisch, S., Bialek, J., Trojanowicz, B., Weber, E., Holzhausen, H.J., Silvertown, J.D., Summerlee, A.J., Dralle, H., Hoang-Vu, C., Klonisch, T. Am. J. Pathol. (2006) [Pubmed]
  5. Characterization of Novel Splice Variants of LGR7 and LGR8 Reveals That Receptor Signaling Is Mediated by Their Unique Low Density Lipoprotein Class A Modules. Scott, D.J., Layfield, S., Yan, Y., Sudo, S., Hsueh, A.J., Tregear, G.W., Bathgate, R.A. J. Biol. Chem. (2006) [Pubmed]
  6. Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism. Figueiredo, K.A., Mui, A.L., Nelson, C.C., Cox, M.E. J. Biol. Chem. (2006) [Pubmed]
  7. Comparison of Signaling Pathways Activated by the Relaxin Family Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes. Halls, M.L., Bathgate, R.A., Summers, R.J. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  8. Multiple binding sites revealed by interaction of relaxin family peptides with native and chimeric relaxin family peptide receptors 1 and 2 (LGR7 and LGR8). Halls, M.L., Bond, C.P., Sudo, S., Kumagai, J., Ferraro, T., Layfield, S., Bathgate, R.A., Summers, R.J. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  9. Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity. Muda, M., He, C., Martini, P.G., Ferraro, T., Layfield, S., Taylor, D., Chevrier, C., Schweickhardt, R., Kelton, C., Ryan, P.L., Bathgate, R.A. Mol. Hum. Reprod. (2005) [Pubmed]
  10. Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle. Bond, C.P., Parry, L.J., Samuel, C.S., Gehring, H.M., Lederman, F.L., Rogers, P.A., Summers, R.J. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  11. Relaxin-3: improved synthesis strategy and demonstration of its high-affinity interaction with the relaxin receptor LGR7 both in vitro and in vivo. Bathgate, R.A., Lin, F., Hanson, N.F., Otvos, L., Guidolin, A., Giannakis, C., Bastiras, S., Layfield, S.L., Ferraro, T., Ma, S., Zhao, C., Gundlach, A.L., Samuel, C.S., Tregear, G.W., Wade, J.D. Biochemistry (2006) [Pubmed]
  12. Comparative localization of leucine-rich repeat-containing G-protein-coupled receptor-7 (RXFP1) mRNA and [33P]-relaxin binding sites in rat brain: restricted somatic co-expression a clue to relaxin action? Ma, S., Shen, P.J., Burazin, T.C., Tregear, G.W., Gundlach, A.L. Neuroscience (2006) [Pubmed]
  13. Evidence for local relaxin ligand-receptor expression and function in arteries. Novak, J., Parry, L.J., Matthews, J.E., Kerchner, L.J., Indovina, K., Hanley-Yanez, K., Doty, K.D., Debrah, D.O., Shroff, S.G., Conrad, K.P. FASEB J. (2006) [Pubmed]
  14. Phosphoinositide 3-kinase activity is required for biphasic stimulation of cyclic adenosine 3',5'-monophosphate by relaxin. Nguyen, B.T., Yang, L., Sanborn, B.M., Dessauer, C.W. Mol. Endocrinol. (2003) [Pubmed]
  15. The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Hsu, S.Y., Kudo, M., Chen, T., Nakabayashi, K., Bhalla, A., van der Spek, P.J., van Duin, M., Hsueh, A.J. Mol. Endocrinol. (2000) [Pubmed]
  16. Demonstration of a relaxin receptor and relaxin-stimulated tyrosine phosphorylation in human lower uterine segment fibroblasts. Palejwala, S., Stein, D., Wojtczuk, A., Weiss, G., Goldsmith, L.T. Endocrinology (1998) [Pubmed]
  17. The low-density lipoprotein class A module of the relaxin receptor (leucine-rich repeat containing G-protein coupled receptor 7): its role in signaling and trafficking to the cell membrane. Kern, A., Agoulnik, A.I., Bryant-Greenwood, G.D. Endocrinology (2007) [Pubmed]
  18. Cloning, expression, and functional characterization of relaxin receptor (leucine-rich repeat-containing g protein-coupled receptor 7) splice variants from human fetal membranes. Kern, A., Hubbard, D., Amano, A., Bryant-Greenwood, G.D. Endocrinology (2008) [Pubmed]
  19. The receptor-binding site of human relaxin II. A dual prong-binding mechanism. Büllesbach, E.E., Yang, S., Schwabe, C. J. Biol. Chem. (1992) [Pubmed]
  20. Receptors for relaxin family peptides. Bathgate, R.A., Ivell, R., Sanborn, B.M., Sherwood, O.D., Summers, R.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  21. Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms. Halls, M.L., Bathgate, R.A., Summers, R.J. Mol. Pharmacol. (2006) [Pubmed]
  22. H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2. Sudo, S., Kumagai, J., Nishi, S., Layfield, S., Ferraro, T., Bathgate, R.A., Hsueh, A.J. J. Biol. Chem. (2003) [Pubmed]
  23. Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells. Tang, M., Mazella, J., Zhu, H.H., Tseng, L. Mol. Hum. Reprod. (2005) [Pubmed]
  24. The Human Relaxin Receptor (LGR7): Expression in the Fetal Membranes and Placenta. Lowndes, K., Amano, A., Yamamoto, S.Y., Bryant-Greenwood, G.D. Placenta (2006) [Pubmed]
  25. An autocrine/paracrine role of human decidual relaxin. I. Interstitial collagenase (matrix metalloproteinase-1) and tissue plasminogen activator. Qin, X., Garibay-Tupas, J., Chua, P.K., Cachola, L., Bryant-Greenwood, G.D. Biol. Reprod. (1997) [Pubmed]
  26. Gene expression pattern and immunoreactive protein localization of LGR7 receptor in human endometrium throughout the menstrual cycle. Luna, J.J., Riesewijk, A., Horcajadas, J.A., Van Os Rd, R., Domínguez, F., Mosselman, S., Pellicer, A., Simón, C. Mol. Hum. Reprod. (2004) [Pubmed]
  27. Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family. Bathgate, R.A., Samuel, C.S., Burazin, T.C., Layfield, S., Claasz, A.A., Reytomas, I.G., Dawson, N.F., Zhao, C., Bond, C., Summers, R.J., Parry, L.J., Wade, J.D., Tregear, G.W. J. Biol. Chem. (2002) [Pubmed]
  28. Relaxin-1-deficient mice develop an age-related progression of renal fibrosis. Samuel, C.S., Zhao, C., Bond, C.P., Hewitson, T.D., Amento, E.P., Summers, R.J. Kidney Int. (2004) [Pubmed]
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