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ADAMTS4

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Target id: 1677

Nomenclature: ADAMTS4

Family: M12: Astacin/Adamalysin

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 837 1q23.3 ADAMTS4 ADAM metallopeptidase with thrombospondin type 1 motif 4
Mouse - 833 1 79.28 cM Adamts4 ADAM metallopeptidase with thrombospondin type 1 motif 4
Rat - 630 13q24 Adamts4 ADAM metallopeptidase with thrombospondin type 1 motif, 4
Previous and Unofficial Names Click here for help
ADMP-1 | aggrecanase-1 | ADAMTS-4 | ADAMTS-2 | ADAM metallopeptidase with thrombospondin type 1 motif, 4 | ADAM metallopeptidase with thrombospondin type 1 motif | a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif
Database Links Click here for help
Specialist databases
MEROPS M12.221 (Hs)
Other databases
Alphafold O75173 (Hs), Q8BNJ2 (Mm), Q9ESP7 (Rn)
BRENDA 3.4.24.82
CATH/Gene3D 2.20.100.10, 3.40.390.10
ChEMBL Target CHEMBL2318 (Hs), CHEMBL4523453 (Rn)
Ensembl Gene ENSG00000158859 (Hs), ENSMUSG00000006403 (Mm), ENSRNOG00000003538 (Rn)
Entrez Gene 9507 (Hs), 240913 (Mm), 66015 (Rn)
Human Protein Atlas ENSG00000158859 (Hs)
KEGG Enzyme 3.4.24.82
KEGG Gene hsa:9507 (Hs), mmu:240913 (Mm), rno:66015 (Rn)
OMIM 603876 (Hs)
Pharos O75173 (Hs)
RefSeq Nucleotide NM_005099 (Hs), NM_172845 (Mm), NM_023959 (Rn)
RefSeq Protein NP_005090 (Hs), NP_766433 (Mm), NP_076449 (Rn)
UniProtKB O75173 (Hs), Q8BNJ2 (Mm), Q9ESP7 (Rn)
Wikipedia ADAMTS4 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.24.82

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 15c [PMID: 21536437] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pIC50 2
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [2]
Immunopharmacology Comments
ADAMTS4 and -5 diminish cartilage integrity in rheumatoid arthritis (RA) by catalysing degradation of aggrecan [3-4].
The activity of ADAMTS4 has been implicated in inducing excessive fibroblast activity and lower respiratory tract tissue damage in viral infection-related acute respiratory distress syndrome (ARDS) [1]. This suggests that inhibition of ADAMTS4 protease activity might be applicable to limit lung damage and improve clinical outcomes following severe respiratory infections.
Immuno Disease Associations
Disease Name:  Rheumatoid arthritis
Disease Synonyms:  no synonynms
Comment:  ADAMTS4 is involved in RA pathogenesis.
Disease X-refs:  Disease Ontology: DOID:7148
OMIM: 180300
References:  3-4
Disease Name:  Osteoarthritis
Disease Synonyms:  no synonynms
Comment:  ADAMTS4 and -5 are major players in development of OA. In human OA ADAMTS4 is induced by IL-1α and TNF-α, two cytokines involved in OA.
Disease X-refs:  Disease Ontology: DOID:8398
References:  5-6

References

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1. Boyd DF, Allen EK, Randolph AG, Guo X-ZJ, Weng Y, Sanders CJ, Bajracharya R, Lee NK, Guy CS, Vogel P et al.. (2020) Exuberant fibroblast activity compromises lung function via ADAMTS. Nature, [Online ahead of print]. DOI: 10.1038/s41586-020-2877-5 [PMID:33116313]

2. De Savi C, Pape A, Sawyer Y, Milne D, Davies C, Cumming JG, Ting A, Lamont S, Smith PD, Tart J et al.. (2011) Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis. Bioorg Med Chem Lett, 21 (11): 3301-6. [PMID:21536437]

3. McInnes IB, Schett G. (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med, 365 (23): 2205-19. [PMID:22150039]

4. Porter S, Clark IM, Kevorkian L, Edwards DR. (2005) The ADAMTS metalloproteinases. Biochem J, 386 (Pt 1): 15-27. [PMID:15554875]

5. Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW. (2007) Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum, 56 (2): 575-85. [PMID:17265492]

6. Yamanishi Y, Boyle DL, Clark M, Maki RA, Tortorella MD, Arner EC, Firestein GS. (2002) Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J Immunol, 168 (3): 1405-12. [PMID:11801682]

How to cite this page

M12: Astacin/Adamalysin: ADAMTS4. Last modified on 29/10/2020. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1677.