PMID- 10438522
OWN - NLM
STAT- MEDLINE
DCOM- 19990901
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 33
DP  - 1999 Aug 13
TI  - Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family.
PG  - 23443-50
AB  - Aggrecan is responsible for the mechanical properties of cartilage. One of the
      earliest changes observed in arthritis is the depletion of cartilage aggrecan due
      to increased proteolytic cleavage within the interglobular domain. Two major
      sites of cleavage have been identified in this region at Asn(341)-Phe(342) and
      Glu(373)-Ala(374). While several matrix metalloproteinases have been shown to
      cleave at Asn(341)-Phe(342), an as yet unidentified protein termed "aggrecanase" 
      is responsible for cleavage at Glu(373)-Ala(374) and is hypothesized to play a
      pivotal role in cartilage damage. We have identified and cloned a novel
      disintegrin metalloproteinase with thrombospondin motifs that possesses
      aggrecanase activity, ADAMTS11 (aggrecanase-2), which has extensive homology to
      ADAMTS4 (aggrecanase-1) and the inflammation-associated gene ADAMTS1. ADAMTS11
      possesses a number of conserved domains that have been shown to play a role in
      integrin binding, cell-cell interactions, and extracellular matrix binding. We
      have expressed recombinant human ADAMTS11 in insect cells and shown that it
      cleaves aggrecan at the Glu(373)-Ala(374) site, with the cleavage pattern and
      inhibitor profile being indistinguishable from that observed with native
      aggrecanase. A comparison of the structure and expression patterns of ADAMTS11,
      ADAMTS4, and ADAMTS1 is also described. Our findings will facilitate the study of
      the mechanisms of cartilage degradation and provide targets to search for
      effective inhibitors of cartilage depletion in arthritic disease.
FAU - Abbaszade, I
AU  - Abbaszade I
AD  - Department of Applied Biotechnology, The DuPont Pharmaceuticals Company,
      Experimental Station, Wilmington, Delaware 19880, USA.
FAU - Liu, R Q
AU  - Liu RQ
FAU - Yang, F
AU  - Yang F
FAU - Rosenfeld, S A
AU  - Rosenfeld SA
FAU - Ross, O H
AU  - Ross OH
FAU - Link, J R
AU  - Link JR
FAU - Ellis, D M
AU  - Ellis DM
FAU - Tortorella, M D
AU  - Tortorella MD
FAU - Pratta, M A
AU  - Pratta MA
FAU - Hollis, J M
AU  - Hollis JM
FAU - Wynn, R
AU  - Wynn R
FAU - Duke, J L
AU  - Duke JL
FAU - George, H J
AU  - George HJ
FAU - Hillman, M C Jr
AU  - Hillman MC Jr
FAU - Murphy, K
AU  - Murphy K
FAU - Wiswall, B H
AU  - Wiswall BH
FAU - Copeland, R A
AU  - Copeland RA
FAU - Decicco, C P
AU  - Decicco CP
FAU - Bruckner, R
AU  - Bruckner R
FAU - Nagase, H
AU  - Nagase H
FAU - Itoh, Y
AU  - Itoh Y
FAU - Newton, R C
AU  - Newton RC
FAU - Magolda, R L
AU  - Magolda RL
FAU - Trzaskos, J M
AU  - Trzaskos JM
FAU - Burn, T C
AU  - Burn TC
AU  - et al.
LA  - eng
SI  - GENBANK/AF142099
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (ADAMTS5 Protein)
RN  - EC 3.4.24.- (ADAMTS5 protein, human)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.99.- (aggrecanase)
SB  - IM
MH  - ADAM Proteins
MH  - ADAMTS5 Protein
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cattle
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Endopeptidases/*genetics/isolation & purification/metabolism
MH  - Humans
MH  - Metalloendopeptidases/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - Recombinant Proteins/genetics/isolation & purification/metabolism
MH  - Sequence Homology, Amino Acid
EDAT- 1999/08/07 10:00
MHDA- 2001/03/28 10:01
CRDT- 1999/08/07 10:00
PHST- 1999/08/07 10:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/08/07 10:00 [entrez]
AID - 10.1074/jbc.274.33.23443 [doi]
AID - S0021-9258(19)65302-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 13;274(33):23443-50. doi: 10.1074/jbc.274.33.23443.