Target Information
Target General Information | Top | |||||
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Target ID |
T14231
(Former ID: TTDR00417)
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Target Name |
Leucine-rich repeat-containing GPCR 5 (LGR5)
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Synonyms |
Orphan G protein-coupled receptor HG38; Leucine-rich repeat-containing G-protein coupled receptor 5; Gpr49; GPR67; G-protein coupled receptor HG38; G-protein coupled receptor 67; G-protein coupled receptor 49; G protein-coupled receptor 49
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Gene Name |
LGR5
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Colorectal cancer [ICD-11: 2B91] | |||||
2 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates 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. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development. Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle.
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BioChemical Class |
GPCR rhodopsin
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UniProt ID | ||||||
Sequence |
MDTSRLGVLLSLPVLLQLATGGSSPRSGVLLRGCPTHCHCEPDGRMLLRVDCSDLGLSEL
PSNLSVFTSYLDLSMNNISQLLPNPLPSLRFLEELRLAGNALTYIPKGAFTGLYSLKVLM LQNNQLRHVPTEALQNLRSLQSLRLDANHISYVPPSCFSGLHSLRHLWLDDNALTEIPVQ AFRSLSALQAMTLALNKIHHIPDYAFGNLSSLVVLHLHNNRIHSLGKKCFDGLHSLETLD LNYNNLDEFPTAIRTLSNLKELGFHSNNIRSIPEKAFVGNPSLITIHFYDNPIQFVGRSA FQHLPELRTLTLNGASQITEFPDLTGTANLESLTLTGAQISSLPQTVCNQLPNLQVLDLS YNLLEDLPSFSVCQKLQKIDLRHNEIYEIKVDTFQQLLSLRSLNLAWNKIAIIHPNAFST LPSLIKLDLSSNLLSSFPITGLHGLTHLKLTGNHALQSLISSENFPELKVIEMPYAYQCC AFGVCENAYKISNQWNKGDNSSMDDLHKKDAGMFQAQDERDLEDFLLDFEEDLKALHSVQ CSPSPGPFKPCEHLLDGWLIRIGVWTIAVLALTCNALVTSTVFRSPLYISPIKLLIGVIA AVNMLTGVSSAVLAGVDAFTFGSFARHGAWWENGVGCHVIGFLSIFASESSVFLLTLAAL ERGFSVKYSAKFETKAPFSSLKVIILLCALLALTMAAVPLLGGSKYGASPLCLPLPFGEP STMGYMVALILLNSLCFLMMTIAYTKLYCNLDKGDLENIWDCSMVKHIALLLFTNCILNC PVAFLSFSSLINLTFISPEVIKFILLVVVPLPACLNPLLYILFNPHFKEDLVSLRKQTYV WTRSKHPSLMSINSDDVEKQSCDSTQALVTFTSSSITYDLPPSSVPSPAYPVTESCHLSS VAFVPCL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | BNC-101 | Drug Info | Phase 1 | Metastatic colorectal cancer | [2] | |
2 | MCLA-158 | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | BNC-102 | Drug Info | Preclinical | Solid tumour/cancer | [4] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 3 Inhibitor drugs | + | ||||
1 | BNC-101 | Drug Info | [5] | |||
2 | MCLA-158 | Drug Info | [6] | |||
3 | BNC-102 | Drug Info | [7] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Wnt signaling pathway | hsa04310 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy |
Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 2.55E-06 |
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Closeness centrality | 1.60E-01 | Radiality | 1.24E+01 | Clustering coefficient | 5.00E-01 |
Neighborhood connectivity | 4.80E+00 | Topological coefficient | 4.80E-01 | Eccentricity | 14 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Affiliated Biological Pathways | Top | |||||
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Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Regulation of FZD by ubiquitination | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | Hair Follicle Development: Cytodifferentiation (Part 3 of 3) |
References | Top | |||||
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REF 1 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 148). | |||||
REF 2 | ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT03526835) A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 4 | Opportunities for therapeutic antibodies directed at G-protein-coupled receptors. Nat Rev Drug Discov. 2017 Sep;16(9):787-810. | |||||
REF 5 | Clinical pipeline report, company report or official report of Bionomics. | |||||
REF 6 | Clinical pipeline report, company report or official report of Merus. | |||||
REF 7 | Opportunities for therapeutic antibodies directed at G-protein-coupled receptors. Nat Rev Drug Discov. 2017 Sep 1;16(9):661. |
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