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A disintegrin & metalloproteinase with thrombospondin type 1 motif 5; ADAMTS-5; ADAM-TS 5; ADAM-TS5; aggrecanase-2; ADMP-2; A disintegrin & metalloproteinase with thrombospondin motifs 11; ADAMTS-11; ADAM-TS 11 (ADAMTS5, ADAMTS11, ADMP2)
Function:
- cleaves aggrecan, a cartilage proteoglycan, & may be involved in its turnover
- may play an important role in destruction of aggrecan in arthritic diseases
- may play a role in proteolytic processing mostly during the peri-implantation period
- precursor is cleaved by a furin endopeptidase
- cleaves aggrecan at the 392-Glu-|-Ala-393 site
Cofactor: binds 1 Zn+2 per subunit (putative)
Structure:
- the spacer domain & the TSP type-1 domains are important for a tight interaction with the extracellular matrix
- the conserved Cys present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme
- dissociation of Cys from Zn+2 upon the activation- peptide release activates the enzyme
- contains 1 disintegrin domain
- contains 1 peptidase M12B domain
- contains 2 TSP type-1 domains
Compartment:
- secreted, extracellular space, extracellular matrix (putative)
Expression:
- expressed at low level in placenta primarily but also detected in heart & brain, cervix, uterus, bladder, esophagus, rib cartilage, fibrous tissue
Pathology:
- expressed in chondroblastoma
- detected in a joint capsule from a patient with osteoarthritis
Related
aggrecan core protein; cartilage-specific proteoglycan core protein; CSPCP; chondroitin sulfate proteoglycan core protein 1; contains: aggrecan core protein 2 (ACAN, AGC1, CSPG1, MSK16)
cartilage
osteoarthritis (OA)
General
A disintegrin & metalloproteinase with thrombospondin type 1 motif (ADAMTS)
glycoprotein
Properties
SIZE: entity length = 930 aa
MW = 102 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-16}
alanine-rich region {37-41}
MOTIF: alanine residue (SEVERAL)
Cysteine switch {207-214}
MOTIF: Zn+2-binding site
SITE: 209-209
arginine-rich region {257-261}
MOTIF: arginine residue (SEVERAL)
Peptidase M12B {267-476}
MOTIF: cysteine residue {C388}
MODIFICATION: cysteine residue {C471}
Zn+2-binding site
SITE: 410-410
glutamate residue {E411}
Zn+2-binding site
SITE: 414-414
Zn+2-binding site
SITE: 420-420
cysteine residue {C426}
MODIFICATION: cysteine residue {C455}
cysteine residue {C455}
MODIFICATION: cysteine residue {C426}
cysteine residue {C471}
MODIFICATION: cysteine residue {C388}
disintegrin domain {485-566}
MOTIF: N-glycosylation site {N498}
TSP1 module {567-622}
MOTIF: cysteine residue {C579}
MODIFICATION: cysteine residue {C616}
cysteine residue {C583}
MODIFICATION: cysteine residue {C621}
cysteine residue {C594}
MODIFICATION: cysteine residue {C606}
cysteine residue {C606}
MODIFICATION: cysteine residue {C594}
cysteine residue {C616}
MODIFICATION: cysteine residue {C579}
cysteine residue {C621}
MODIFICATION: cysteine residue {C583}
cysteine-rich region {624-731}
MOTIF: N-glycosylation site {N728}
Spacer {732-874}
MOTIF: N-glycosylation site {N802}
N-glycosylation site {N807}
TSP1 module {875-929}
Database Correlations
OMIM 605007
UniProt Q9UNA0
PFAM correlations
Entrez Gene 11096
Kegg hsa:11096
References
- UniProt :accession Q9UNA0
- Journal Watch 25(10):81, 2005
Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL,
Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA.
Deletion of active ADAMTS5 prevents cartilage degradation in
a murine model of osteoarthritis.
Nature. 2005 Mar 31;434(7033):644-8.
PMID: 15800624
- Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE,
Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM,
Fosang AJ.
ADAMTS5 is the major aggrecanase in mouse cartilage in vivo
and in vitro.
Nature. 2005 Mar 31;434(7033):648-52.
PMID: 15800625