Entry Name Relaxin signaling pathway - Sciurus carolinensis (gray squirrel)
Description Human relaxin-2 ("relaxin"), originally identified as a peptidic hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic and angiogenic effects in both males and females. It belongs to the so-called relaxin peptide family which includes the insulin-like peptides INSL3 and INSL5, and relaxin-3 (H3) as well as relaxin. INSL3 has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. These members of relaxin peptide family exert such effects binding to different kinds of receptors, classified as relaxin family peptide (RXFP) receptors: RXFP1, RXFP2, RXFP3, and RXFP4. These G protein-coupled receptors predominantly bind relaxin, INSL3, relaxin-3, and INSL-5, respectively. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Both RXFP3 and RXFP4 inhibit cAMP production, and RXFP3 activate MAP kinases.
Class Organismal Systems; Endocrine systemBRITE hierarchy
Pathway map Ortholog table Organism Sciurus carolinensis (gray squirrel) [GN:
ncar ]
Gene 124967520 guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
124992673 guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
124988012 guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
124991078 guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
124975134 guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632 ]
124976089 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
124969987 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
124993231 guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538 ]
124960444 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
124961969 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
124978139 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
124961463 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
124961876 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542 ]
124965653 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542 ]
124968657 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
124967414 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544 ]
124970655 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10-like [KO:K04545 ]
124964520 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
124975713 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
124991054 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
124993726 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
124969192 putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347 ]
124990131 guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548 ]
124980134 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 isoform X1 [KO:K04549 ]
124979032 cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
124979831 LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2-like [KO:K04450 ]
124991113 cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
124958938 cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
124984689 cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
124969564 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
124964377 cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048 ]
124991182 cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
124988573 cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
124963509 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
124986648 phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
124968815 phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
124967085 transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
124980435 LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430 ] [EC:2.7.12.2 ]
124968935 guanine nucleotide-binding protein subunit alpha-15 isoform X1 [KO:K04637 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Bathgate RA, Halls ML, van der Westhuizen ET, Callander GE, Kocan M, Summers RJ
Title Relaxin family peptides and their receptors.
Journal Reference Authors Cernaro V, Lacquaniti A, Lupica R, Buemi A, Trimboli D, Giorgianni G, Bolignano D, Buemi M
Title Relaxin: new pathophysiological aspects and pharmacological perspectives for an old protein.
Journal Reference Authors van der Westhuizen ET, Halls ML, Samuel CS, Bathgate RA, Unemori EN, Sutton SW, Summers RJ
Title Relaxin family peptide receptors--from orphans to therapeutic targets.
Journal Reference Authors Halls ML, van der Westhuizen ET, Bathgate RA, Summers RJ
Title Relaxin family peptide receptors--former orphans reunite with their parent ligands to activate multiple signalling pathways.
Journal Reference Authors Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ
Title International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides.
Journal Reference Authors Du XJ, Bathgate RA, Samuel CS, Dart AM, Summers RJ
Title Cardiovascular effects of relaxin: from basic science to clinical therapy.
Journal Reference Authors Nistri S, Bani D
Title Relaxin receptors and nitric oxide synthases: search for the missing link.
Journal Reference Authors Samuel CS, Hewitson TD, Unemori EN, Tang ML
Title Drugs of the future: the hormone relaxin.
Journal Reference Authors Sasser JM
Title The emerging role of relaxin as a novel therapeutic pathway in the treatment of chronic kidney disease.
Journal Reference Authors Sarwar M, Du XJ, Dschietzig TB, Summers RJ
Title The actions of relaxin on the human cardiovascular system.
Journal Reference Authors Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ
Title Receptors for relaxin family peptides.
Journal Reference Authors Chow BS, Chew EG, Zhao C, Bathgate RA, Hewitson TD, Samuel CS
Title Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: the additional involvement of iNOS.
Journal Reference Authors Samuel CS, Du XJ, Bathgate RA, Summers RJ
Title 'Relaxin' the stiffened heart and arteries: the therapeutic potential for relaxin in the treatment of cardiovascular disease.
Journal Reference Authors Wilson SS, Ayaz SI, Levy PD
Title Relaxin: a novel agent for the treatment of acute heart failure.
Journal Reference Authors Halls ML, Bathgate RA, Summers RJ
Title Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms.
Journal Reference Authors Kocan M, Ang SY, Summers RJ
Title Orthosteric, Allosteric and Biased Signalling at the Relaxin-3 Receptor RXFP3.
Journal Reference Authors van der Westhuizen ET, Werry TD, Sexton PM, Summers RJ
Title The relaxin family peptide receptor 3 activates extracellular signal-regulated kinase 1/2 through a protein kinase C-dependent mechanism.
Journal Related KO pathway LinkDB All DBs
