Molecular Cloning of a Gene Encoding a New Type of Metalloproteinase-disintegrin Family Protein with Thrombospondin Motifs as an Inflammation Associated Gene*

By K. Kuno, Naomi Kanada, E. Nakashima, Fujio Fujiki, F. Ichimura, K. Matsushima. 1997

A cellular disintegrin and metalloproteinase (ADAM) is a new family of genes with structural homology to the snake venom metalloproteinases and disintegrins. We screened genes which were selectively expressed in the cachexigenic colon 26 adenocarcinoma subline in vivo. It was found that one novel cDNA clone, identified as a cachexigenic tumor selective gene, encodes a cysteine-rich protein which shows a sequence similarity to that of both the snake venom metalloproteinases and thrombospondins. We named this cDNA clone isintegrin nd etalloproteinase with hrombopondin motifs (ADAMTS-1). ADAMTS1 consists of six domains, 1) a pro- and 2) a metalloproteinase, 3) a disintegrin-like, 4) a thrombospondin (TSP) homologous domain containing TSP type I motif, 5) a spacer region, and 6) COOH-terminal TSP submotifs. Unlike other ADAMs, ADAMTS-1 does not possess a transmembrane domain and is a putative secretory protein. Therefore, ADAMTS-1 is a new type of ADAM family protein with TSP type I motifs. We demonstrated that the TSP homologous domain containing the TSP type I motif of ADAMTS-1 is functional for binding to heparin. ADAMTS-1 mRNA could be induced by stimulating colon 26 cells with an inflammatory cytokine, interleukin-1, in vitro. Moreover, intravenous administration of lipopolysaccharide in mice selectively induced ADAMTS-1 mRNA in kidney and heart. These data suggest that ADAM-TS-1 may be a gene whose expression is associated with various inflammatory processes as well as development of cancer cachexia.

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Citations in the corpus

• A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “ADAMTS family was first identified as an inflammation factor in 1997 [10].”
• ADAM and ADAMTS gene expression in native and wound healing human lens epithelial cells (2010, background): “Since the discovery of the first ADAMTS in 1997, 19 human ADAMTS family members have been described [8,9].”
• ADAM 23/MDC3, a Human Disintegrin That Promotes Cell Adhesion via Interaction with the αvβ3 Integrin through an RGD-independent Mechanism (2000, unknown): “Similarly, ADAMTS-1, characterized by the presence of thrombospondin motifs in its amino acid sequence, has been associated with various inflammatory processes (Kuno et al., 1997).”
• Genetic association between polymorphisms in the BTG1 gene and multiple sclerosis. (2005, unknown): “A presumably complementing role in controlling brain matrix structure and organization has been ascribed to the novel protease family A Disintegrin And Metalloproteinase Domain with Thrombospondin Motifs (ADAMTS) (Kuno et al., 1997; Kuno and Matsushima, 1998; Kuno et al., 1999).”
• Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinases. (2000, methodology): “The discovery that an ADAMTS-metalloproteinase (Kuno et al., 1997) is essential for nematode gonadogenesis highlights the possibility of repetitive cleavage, as well as synthesis, of pericellular ECM during organogenesis (Blelloch and Kimble, 1999).”
• Expression of ADAMTS1 and Its Correlation with Angiogenesis in Primary Gastric Cancer and Lymph Node Metastasis (2013, background): “In addition, it contains three thrombospondin type I motifs (TSP1), which are important for its angioinhibitory effects [24].”