A disintegrin & metalloproteinase with thrombospondin type 1 motif 4; ADAMTS-4; ADAM-TS 4; ADAM-TS4; aggrecanase-1; ADMP-1 (ADAMTS4, KIAA0688, UNQ769/PRO1563)

Function

• cleaves aggrecan, a cartilage proteoglycan, & may be involved in its turnover
• cleaves aggrecan at the '392-Glu-|-Ala-393' site
• precursor is cleaved by a furin endopeptidase
• glutamyl endopeptidase; bonds cleaved include 370-Thr-Glu-Gly-Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian aggrecan

Cofactor: binds 1 Zn+2 per subunit (putative)

Structure

• spacer domain & the TSP type-1 domains are important for a tight interaction with the extracellular matrix
• conserved Cys present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme
• dissociation of Cys from the Zn+2 upon activation- peptide release activates the enzyme
• contains 1 disintegrin domain
• contains 1 peptidase M12B domain
• contains 1 TSP type-1 domain

Compartment

• secreted, extracellular space, extracellular matrix (putative)

Expression

• expressed in brain, lung & heart
• expressed at very low level in placenta & skeletal muscles
• induced by interleukin-1

Pathology

• may play a role in destruction of aggrecan in osteoarthritis
• may play a role in neurodegeneration in Alzheimer disease

Notes

Has sometimes been referred to as ADAMTS2

More general terms

• ADAMTS protease
• glycoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9507
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9507
• OMIM: https://mirror.omim.org/entry/603876
• UniProt: http://www.uniprot.org/uniprot/O75173.html