ADAMTS7B, the Full-length Product of the ADAMTS7 Gene, Is a Chondroitin Sulfate Proteoglycan Containing a Mucin Domain*

By R. Somerville, Jean-Michel Longpré, E. D. Apel, Renate M. Lewis, Lauren W. Wang, J. Sanes, R. Leduc, S. Apte. 2004

107 citations recorded by the source corpus.

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 Arg220 (mouse sequence annotation), occurs at the cell surface. ADAMTS7B is an active metalloproteinase as shown by its ability to cleave α2-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.

Subfields: Cancer Research, Hematology, Immunology and Allergy

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In Cancer Research

1. S. Zhong
2. S. Apte
3. R. Khalil

In Hematology

1. S. Zhong
2. R. Khalil
3. X. L. Zheng

In Immunology and Allergy

1. S. Zhong
2. R. Khalil
3. T. Mead
4. S. Apte

Citations in the corpus

• A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “These serine proteases efficiently cleave after a consensus sequence Arg-Xaa-(Arg/Lys)-Arg, and the cleavage likely occurs in the trans-Golgi or at the cell surface [36, 37].”
• ADAMTS proteins in human disorders (2018, background): “Expression of ADAMTS7 constructs carrying the Pro (G) substitution [77] demonstrated reduced furin-mediated ADAMTS7 propeptide excision, which occurs at the cell-surface [78] and is presumably an activating step.”
• Knockout of Adamts7, A Novel CAD Locus in Humans, Reduces Atherosclerosis in Mice (2015, background): “ADAMTS7 is a member of the ADAMTS family of secreted zinc metalloproteases with characteristic protein domain composition, including at least 1 thrombospondin type I repeat.(6,7) These proteins have highly homologous N-terminal protein domain structure and organization, but the C-terminal halves var”
• Biochemistry and physiological functions of ADAMTS7 metalloprotease (2013, background): “PGRN, also known as plasma cell-derived growth factor, progranulin, acrogranin, or GP80 [27-29], binds ADAMTS7 and inhibits its proteolytic activity towards COMP [30].”