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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
Note: Has sometimes been referred to as ADAMTS2
General
A disintegrin & metalloproteinase with thrombospondin type 1 motif (ADAMTS)
glycoprotein
Properties
SIZE: entity length = 837 aa
MW = 90 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-51}
N-glycosylation site {N68}
Cysteine switch {192-199}
MOTIF: Zn+2-binding site
SITE: 194-194
Peptidase M12B {218-428}
MOTIF: alanine-rich region {247-252}
MOTIF: alanine residue (SEVERAL)
cysteine residue {C339}
MODIFICATION: cysteine residue {C423}
Zn+2-binding site
SITE: 361-361
glutamate residue {E362}
Zn+2-binding site
SITE: 365-365
Zn+2-binding site
SITE: 371-371
cysteine residue {C377}
MODIFICATION: cysteine residue {C407}
cysteine residue {C407}
MODIFICATION: cysteine residue {C377}
cysteine residue {C423}
MODIFICATION: cysteine residue {C339}
disintegrin domain {437-519}
TSP1 module {520-575}
MOTIF: cysteine residue {C532}
MODIFICATION: cysteine residue {C569}
cysteine residue {C536}
MODIFICATION: cysteine residue {C574}
cysteine residue {C547}
MODIFICATION: cysteine residue {C559}
cysteine residue {C559}
MODIFICATION: cysteine residue {C547}
cysteine residue {C569}
MODIFICATION: cysteine residue {C532}
cysteine residue {C574}
MODIFICATION: cysteine residue {C536}
cysteine-rich region {577-685}
Spacer {686-837}
Database Correlations
OMIM 603876
UniProt O75173
PFAM correlations
Entrez Gene 9507
Kegg hsa:9507
ENZYME 3.4.24.82
References
UniProt :accession O75173