Entry Name Relaxin signaling pathway - Delphinapterus leucas (beluga whale)
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 Organism Delphinapterus leucas (beluga whale) [GN:
dle ]
Gene 111163963 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
111164599 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
111165310 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
111165617 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
111165653 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
111166107 GNA15; guanine nucleotide-binding protein subunit alpha-15 isoform X1 [KO:K04637 ]
111166195 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
111166309 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549 ]
111166652 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
111166783 GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347 ]
111167181 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
111170918 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
111170946 ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
111171769 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
111172890 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
111173161 GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826 ]
111173828 GNB4; guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538 ]
111173839 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
111174368 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
111176694 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 isoform X1 [KO:K07825 ]
111177332 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
111177624 GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539 ]
111177962 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
111178318 INSL5; LOW QUALITY PROTEIN: insulin-like peptide INSL5 [KO:K22001 ]
111178375 GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
111178437 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
111178866 VEGFA; vascular endothelial growth factor A isoform X1 [KO:K05448 ]
111179110 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
111179235 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
111180070 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
111180225 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
111180709 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544 ]
111180824 TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
111181049 GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
111181753 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
111181977 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
111183022 GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548 ]
111183816 VEGFB; vascular endothelial growth factor B isoform X1 [KO:K16858 ]
111183856 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
111183987 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
111185128 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
111185984 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
111186212 ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374 ]
111186741 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632 ]
111187055 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
111187262 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
111188007 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
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 dle04270 Vascular smooth muscle contraction
KO pathway
