Entry Name Relaxin signaling pathway - Acinonyx jubatus (cheetah)
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 Acinonyx jubatus (cheetah) [GN:
aju ]
Gene 106973284 guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534 ]
106977809 guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
106982494 guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
106969942 guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632 ]
106984654 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
106987417 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
106965344 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825 ]
106967264 guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539 ]
106981966 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826 ]
113593204 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3-like [KO:K04540 ]
106981725 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
106982557 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 isoform X3 [KO:K04541 ]
106970626 LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
106973348 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
106989697 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
113593434 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544 ]
113592841 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
106969997 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
106985197 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
113596552 putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 isoform X3 [KO:K04347 ]
106977369 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 isoform X1 [KO:K04547 ]
106969996 guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548 ]
106985188 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 isoform X1 [KO:K04549 ]
106967098 cyclic AMP-responsive element-binding protein 1 isoform X3 [KO:K05870 ]
106988085 cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
106970423 cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
106987262 cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
106975473 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
106978069 cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
106987665 cyclic AMP-responsive element-binding protein 5 isoform X6 [KO:K09047 ]
106983500 cyclic AMP-dependent transcription factor ATF-6 beta isoform X4 [KO:K09049 ]
106984896 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
106984265 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
106976917 phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649 ]
106973297 LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
106969150 phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
106987682 transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
106982148 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 aju04270 Vascular smooth muscle contraction
KO pathway LinkDB All DBs
