Entry |
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Name |
Relaxin signaling pathway - Homo sapiens (human)
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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.
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Class |
Organismal Systems; Endocrine system
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Pathway map |

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Disease |
H02241 | Ehlers-Danlos syndrome cardiac valvular type |
H02242 | Ehlers-Danlos syndrome vascular type |
H02243 | Ehlers-Danlos syndrome arthrochalasia type |
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Drug |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
59350 | RXFP1; relaxin family peptide receptor 1 [KO:K04306] |
2775 | GNAO1; G protein subunit alpha o1 [KO:K04534] |
2770 | GNAI1; G protein subunit alpha i1 [KO:K04630] |
2773 | GNAI3; G protein subunit alpha i3 [KO:K04630] |
2771 | GNAI2; G protein subunit alpha i2 [KO:K04630] |
2790 | GNG10; G protein subunit gamma 10 [KO:K04545] |
2791 | GNG11; G protein subunit gamma 11 [KO:K04546] |
2792 | GNGT1; G protein subunit gamma transducin 1 [KO:K04548] |
2793 | GNGT2; G protein subunit gamma transducin 2 [KO:K04549] |
1385 | CREB1; cAMP responsive element binding protein 1 [KO:K05870] |
1386 | ATF2; activating transcription factor 2 [KO:K04450] |
468 | ATF4; activating transcription factor 4 [KO:K04374] |
10488 | CREB3; cAMP responsive element binding protein 3 [KO:K09048] |
90993 | CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048] |
64764 | CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048] |
84699 | CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048] |
148327 | CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048] |
9586 | CREB5; cAMP responsive element binding protein 5 [KO:K09047] |
1388 | ATF6B; activating transcription factor 6 beta [KO:K09049] |
7422 | VEGFA; vascular endothelial growth factor A [KO:K05448] |
7423 | VEGFB; vascular endothelial growth factor B [KO:K16858] |
7424 | VEGFC; vascular endothelial growth factor C [KO:K05449] |
2277 | VEGFD; vascular endothelial growth factor D [KO:K05449] |
4790 | NFKB1; nuclear factor kappa B subunit 1 [KO:K02580] |
5970 | RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735] |
5290 | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
5293 | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
5291 | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
5295 | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
5296 | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
8503 | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
1910 | EDNRB; endothelin receptor type B [KO:K04198] |
4322 | MMP13; matrix metallopeptidase 13 [KO:K07994] [EC:3.4.24.-] |
7040 | TGFB1; transforming growth factor beta 1 [KO:K13375] |
59 | ACTA2; actin alpha 2, smooth muscle [KO:K12313] |
1277 | COL1A1; collagen type I alpha 1 chain [KO:K06236] |
1278 | COL1A2; collagen type I alpha 2 chain [KO:K06236] |
1281 | COL3A1; collagen type III alpha 1 chain [KO:K19720] |
1284 | COL4A2; collagen type IV alpha 2 chain [KO:K06237] |
1286 | COL4A4; collagen type IV alpha 4 chain [KO:K06237] |
1288 | COL4A6; collagen type IV alpha 6 chain [KO:K06237] |
1282 | COL4A1; collagen type IV alpha 1 chain [KO:K06237] |
1287 | COL4A5; collagen type IV alpha 5 chain [KO:K06237] |
1285 | COL4A3; collagen type IV alpha 3 chain [KO:K06237] |
51289 | RXFP3; relaxin family peptide receptor 3 [KO:K08397] |
3725 | JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448] |
2353 | FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379] |
3265 | HRAS; HRas proto-oncogene, GTPase [KO:K02833] |
3845 | KRAS; KRAS proto-oncogene, GTPase [KO:K07827] |
4893 | NRAS; NRAS proto-oncogene, GTPase [KO:K07828] |
6654 | SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099] |
6655 | SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099] |
2885 | GRB2; growth factor receptor bound protein 2 [KO:K04364] |
339403 | RXFP4; relaxin family peptide/INSL5 receptor 4 [KO:K08398] |
2769 | GNA15; G protein subunit alpha 15 [KO:K04637] |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Bathgate RA, Halls ML, van der Westhuizen ET, Callander GE, Kocan M, Summers RJ |
Title |
Relaxin family peptides and their receptors. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Du XJ, Bathgate RA, Samuel CS, Dart AM, Summers RJ |
Title |
Cardiovascular effects of relaxin: from basic science to clinical therapy. |
Journal |
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Reference |
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Authors |
Nistri S, Bani D |
Title |
Relaxin receptors and nitric oxide synthases: search for the missing link. |
Journal |
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Reference |
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Authors |
Samuel CS, Hewitson TD, Unemori EN, Tang ML |
Title |
Drugs of the future: the hormone relaxin. |
Journal |
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Reference |
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Authors |
Sasser JM |
Title |
The emerging role of relaxin as a novel therapeutic pathway in the treatment of chronic kidney disease. |
Journal |
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Reference |
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Authors |
Sarwar M, Du XJ, Dschietzig TB, Summers RJ |
Title |
The actions of relaxin on the human cardiovascular system. |
Journal |
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Reference |
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Authors |
Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ |
Title |
Receptors for relaxin family peptides. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Wilson SS, Ayaz SI, Levy PD |
Title |
Relaxin: a novel agent for the treatment of acute heart failure. |
Journal |
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Reference |
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Authors |
Halls ML, Bathgate RA, Summers RJ |
Title |
Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms. |
Journal |
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Reference |
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Authors |
Kocan M, Ang SY, Summers RJ |
Title |
Orthosteric, Allosteric and Biased Signalling at the Relaxin-3 Receptor RXFP3. |
Journal |
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Reference |
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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 |
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Related pathway |
hsa04270 | Vascular smooth muscle contraction |
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KO pathway |
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LinkDB |
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