Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7HJTF)

DTT Name	R-spondin-3 (RSPO3)
Synonyms	hRspo3; hPWTSR; Thrombospondin type-1 domain-containing protein 2; Roof plate-specific spondin-3; Protein with TSP type-1 repeat
Gene Name	RSPO3
DTT Type	Clinical trial target	[1]
BioChemical Class	R-spondin family
UniProt ID	RSPO3_HUMAN
TTD ID	T79162
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Sequence	MHLRLISWLFIILNFMEYIGSQNASRGRRQRRMHPNVSQGCQGGCATCSDYNGCLSCKPR LFFALERIGMKQIGVCLSSCPSGYYGTRYPDINKCTKCKADCDTCFNKNFCTKCKSGFYL HLGKCLDNCPEGLEANNHTMECVSIVHCEVSEWNPWSPCTKKGKTCGFKRGTETRVREII QHPSAKGNLCPPTNETRKCTVQRKKCQKGERGKKGRERKRKKPNKGESKEAIPDSKSLES SKEIPEQRENKQQQKKRKVQDKQKSVSVSTVH
Function	Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells. Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3.
KEGG Pathway	Wnt signaling pathway (hsa04310 )
Reactome Pathway	RUNX1 regulates transcription of genes involved in WNT signaling (R-HSA-8939256 ) Regulation of FZD by ubiquitination (R-HSA-4641263 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
OMP-131R10	DMTFU8Q	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
Rosmantuzumab	DM9O3RY	Colorectal cancer	2B91.Z	Phase 1	[1]
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References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	Targeting the Wnt signaling pathway through R-spondin 3 identifies an anti-fibrosis treatment strategy for multiple organs. PLoS One. 2020 Mar 11;15(3):e0229445.