Entry
Name
Relaxin signaling pathway - Pan troglodytes (chimpanzee)
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 system
BRITE hierarchy
Pathway map
Ortholog table
Organism
Pan troglodytes (chimpanzee) [GN:
ptr ]
Gene
450173 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534 ]
457093 GNAI3; guanine nucleotide-binding protein G(I) subunit alpha-3 [KO:K04630 ]
472425 GNAI1; guanine nucleotide-binding protein G(I) subunit alpha-1 isoform X1 [KO:K04630 ]
744773 GNAI2; guanine nucleotide-binding protein G(I) subunit alpha-2 [KO:K04630 ]
469986 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X4 [KO:K04632 ]
469458 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
739897 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
100612078 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825 ]
460862 GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538 ]
745402 GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539 ]
467457 GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826 ]
740869 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
743331 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
456977 GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
129136331 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
744391 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
107969769 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X2 [KO:K04544 ]
100611518 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
129137227 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
747185 GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
100609242 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 isoform X1 [KO:K04347 ]
107969673 GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347 ]
107968762 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
747170 GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548 ]
749133 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549 ]
469367 PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X6 [KO:K04345 ] [EC:2.7.11.11 ]
459901 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
101059354 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
744513 ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374 ]
451704 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048 ]
468672 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X4 [KO:K09048 ]
738928 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
457341 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
465081 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
463318 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X11 [KO:K09047 ]
107975108 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X3 [KO:K09049 ]
736875 VEGFA; vascular endothelial growth factor A, long form isoform X1 [KO:K05448 ]
741897 VEGFB; vascular endothelial growth factor B isoform X1 [KO:K16858 ]
471358 VEGFC; vascular endothelial growth factor C [KO:K05449 ]
465508 VEGFD; vascular endothelial growth factor D [KO:K05449 ]
461406 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580 ]
460858 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
457922 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
471079 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
456565 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649 ]
461836 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649 ]
460182 RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366 ] [EC:2.7.11.1 ]
456060 TGFB1; transforming growth factor beta-1 proprotein isoform X3 [KO:K13375 ]
455407 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
452659 COL4A1; collagen alpha-1(IV) chain isoform X1 [KO:K06237 ]
459986 COL4A4; collagen alpha-4(IV) chain isoform X1 [KO:K06237 ]
465804 COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237 ]
452661 COL4A2; collagen alpha-2(IV) chain isoform X1 [KO:K06237 ]
459988 COL4A3; collagen alpha-3(IV) chain isoform X4 [KO:K06237 ]
748892 JAK3; tyrosine-protein kinase JAK3 precursor [KO:K21999 ]
453330 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
458093 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X5 [KO:K05858 ] [EC:3.1.4.11 ]
469875 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
451290 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
455065 MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X4 [KO:K04430 ] [EC:2.7.12.2 ]
743199 MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X3 [KO:K04431 ] [EC:2.7.12.2 ]
457351 SHC1; SHC-transforming protein 1 isoform X8 [KO:K06279 ]
749831 SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447 ]
450176 SHC3; SHC-transforming protein 3 isoform X2 [KO:K17448 ]
453414 SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449 ]
459171 SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099 ]
452897 SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099 ]
737245 GRB2; growth factor receptor-bound protein 2 [KO:K04364 ]
744860 GNA15; 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 pathway
ptr04270 Vascular smooth muscle contraction
KO pathway
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