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HtrA1, a 51KDa protein, is a member of highly conserved mammalian HtrA serine protease family. It is a human homolog of bacterial HtrA and consists of a secretory signal sequence, an IGFBP-binding domain and a Kazal-type serine-protease inhibitor domain at the N-terminus and a highly conserved trypsin-like serine/protease domain and a PDZ domain at the C-terminus. It plays a major role in the regulation of cell growth. HtrA1 inhibits signaling mediated by TGF-beta family members and regulates many physiological processes. HtrA1 is up-regulated in placenta during pregnancy and plays an important role in implantation and placental physiology. It regulates the availability of IGFs by cleaving IGF-binding proteins. It acts as a tumor suppressor and is down-regulated in ovarian cancers and melanomas. Its role has been implicated in osteoarthritis suggesting a therapeutic intervention. Northern blot analysis detected high expression in placenta.
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