ADAMTS7B, the full-length product of the ADAMTS7 gene, is a chondroitin sulfate proteoglycan containing a mucin domain.
We have characterized ADAMTS7B, the authentic full-length protein product of the ADAMTS7 gene. ADAMTS7B has a domain organization similar to that of ADAMTS12, with a total of eight thrombospondin type 1 repeats in its ancillary domain. Of these, seven are arranged in two distinct clusters that are separated by a mucin domain. Unique to the ADAMTS family, ADAMTS7B is modified by attachment of the glycosaminoglycan chondroitin sulfate within the mucin domain, thus rendering it a proteoglycan. Glycosaminoglycan addition has potentially important implications for ADAMTS7B cellular localization and for substrate recognition. Although not an integral membrane protein, ADAMTS7B is retained near the cell surface of HEK293F cells via interactions involving both the ancillary domain and the prodomain. ADAMTS7B undergoes removal of the prodomain by a multistep furin-dependent mechanism. At least part of the final processing event, i.e. cleavage following Arg(220) (mouse sequence annotation), occurs at the cell surface. ADAMTS7B is an active metalloproteinase as shown by its ability to cleave alpha(2)-macroglobulin, but it does not cleave specific peptide bonds in versican and aggrecan attacked by ADAMTS proteases. Together with ADAMTS12, whose primary structure also predicts a mucin domain, ADAMTS7B constitutes a unique subgroup of the ADAMTS family.
Somerville
Robert P T
RP
Department of Biomedical Engineering, Lerner Research Institute, Orthopedic Research Center, Cleveland Clinic Foundation, Ohio 44195, USA.
Longpré
Jean-Michel
JM
Apel
Elizabeth D
ED
Lewis
Renate M
RM
Wang
Lauren W
LW
Sanes
Joshua R
JR
Leduc
Richard
R
Apte
Suneel S
SS
D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D000071118:ADAMTS7 Protein; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics*; D045726:Metalloproteases / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009077:Mucins / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D019700:Thrombospondin 1 / Q000235:genetics
D011508:Chondroitin Sulfate Proteoglycans; D018076:DNA, Complementary; D009077:Mucins; D019700:Thrombospondin 1; D045726:Metalloproteases; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C496252:ADAMTS12 protein, human; D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human; C496264:Adamts7 protein, mouse; D008666:Metalloendopeptidases