ADAMTS9, a Novel Member of the ADAM-TS/ Metallospondin Gene Family

Clark, Mary C.; Kelner, Gregory S.; Turbeville, Laurie A.; Boyer, Antonia; Arden, Karen C.; Maki, Richard A.

doi:10.1006/geno.2000.6246

Cited by 93 publications

(79 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Members of the ADAM-TS family have been implicated in the cleavage of proteoglycans, control of organ shape during development, and the inhibition of angiogenesis (Clark et al, 2000). Downregulated expression of ADAMTS9 was also found in breast carcinoma (Porter et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9

Leung

Kwok

et al. 2006

Oncogene

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9

Leung

Kwok

et al. 2006

Oncogene

View full text Add to dashboard Cite

“…Analysis of expressed sequence tags in the GenBank TM /EBI Data Bank validated the sequence of ADAMTS7B, but no expressed sequence tag with the 3Ј-sequence of ADAMTS7A was found. Incidentally, intron retention confounded the initial characterization of ADAMTS6, ADAMTS9, ADAMTS16, and ADAMTS18 (18,36,37), and longer ORFs have subsequently been identified (13). 3 The ADAMTS7A transcript is unlikely to be an alternatively spliced product.…”

Section: Discussionmentioning

confidence: 99%

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

Somerville

Longpré

Apel

et al. 2004

Journal of Biological Chemistry

111

View full text Add to dashboard Cite

We have characterized ADAMTS7B, the authentic fulllength 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 ␣ 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. The extracellular matrix (ECM)1 is an information-rich assembly influencing cell proliferation, apoptosis, and cell migration. Proteases have an essential role in modulating the environmental cues that ECM provides for tissue morphogenesis, homeostasis, and disease progression. Metalloproteases, especially matrix metalloproteases, have a conspicuous role in ECM degradation as well as in proteolysis of cell-surface and soluble proteins (1, 2). Another metalloprotease family, ADAM (a disintegrin and metalloprotease domain), contains transmembrane enzymes with a major role in ectodomain shedding of cell-surface molecules, but a negligible function in ECM proteolysis (3). The active site of ADAM proteases, unlike that of the matrix metalloproteases, is of the reprolysin (snake venom zinc metalloprotease) type (3). The recent discovery of the ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin type 1 motif) family brought to light metalloproteases that contain a reprolysintype catalytic site, but, unlike the ADAM proteases, are secreted enzymes with a prominent role in ECM proteolysis.ADAMTS proteases have a characteristic modular structure whose hallmark is the presence of one or more thrombospondin type 1 repeats (TSRs) (4). In the short period of time since the discovery of ADAMTS1 in 1997 (4), important functions have been attributed to a number of family members, and mutations of two of these enzymes have been shown to cause human genetic disorders. Inactivating mutations of ADAMTS13 cause inherited thrombocytopenic purpura due to a failure to process von Willebrand factor (5). Mutations of ADAMTS2, a procollagen aminopropeptidase, cause skin fragility in a var...

show abstract

“…Despite being a much smaller enzyme than GON-1, it had greater sequence similarity to it than to any other human ADAMTS (17). Here, we characterize a considerably longer form of ADAMTS-9 (designated ADAMTS-9B, but referred to subsequently in this paper as ADAMTS-9) that we propose is the authentic full-length product of ADAMTS9.…”

mentioning

confidence: 88%

Characterization of ADAMTS-9 and ADAMTS-20 as a Distinct ADAMTS Subfamily Related to Caenorhabditis elegans GON-1

Somerville

Longpré

Jungers

et al. 2003

Journal of Biological Chemistry

308

332

View full text Add to dashboard Cite

We demonstrate that in humans, two metalloproteases, ADAMTS-9 (1935 amino acids) and ADAMTS-20 (1911 amino acids) are orthologs of GON-1, an ADAMTS protease required for gonadal morphogenesis in Caenorhabditis elegans. ADAMTS-9 and ADAMTS-20 have an identical modular structure, are distinct in possessing 15 TSRs and a unique C-terminal domain, and have a similar gene structure, suggesting that they comprise a new subfamily of human ADAMTS proteases. AD-AMTS20 is very sparingly expressed, although it is detectable in epithelial cells of the breast and lung. However, ADAMTS9 is highly expressed in embryonic and adult tissues, and therefore we characterized the AD-AMTS-9 protein further. Although the ADAMTS-9 zymogen has many proprotein convertase processing sites, pulse-chase analysis, site-directed mutagenesis, and amino acid sequencing demonstrated that maturation to the active form occurs by selective proprotein convertase (e.g. furin) cleavage of the Arg 287 -Phe 288 bond. Although lacking a transmembrane sequence, ADAMTS-9 is retained near the cell surface as well as in the ECM of transiently transfected COS-1 and 293 cells. COS-1 cells transfected with ADAMTS9 (but not vector-transfected cells) proteolytically cleaved bovine versican and aggrecan core proteins at the Glu 441 -Ala 442 bond of versican V1 and the Glu 1771 -Ala 1772 bond of aggrecan, respectively. In contrast, the ADAMTS-9 catalytic domain alone was neither localized to the cell surface nor able to confer these proteolytic activities on cells, demonstrating that the ancillary domains of ADAMTS-9, including the TSRs, are required both for specific extracellular localization and for its versicanase and aggrecanase activities.

show abstract

ADAMTS9, a Novel Member of the ADAM-TS/ Metallospondin Gene Family

Cited by 93 publications

References 40 publications

Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9

Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9

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

Characterization of ADAMTS-9 and ADAMTS-20 as a Distinct ADAMTS Subfamily Related to Caenorhabditis elegans GON-1

Contact Info

Product

Resources

About