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HtrA3, also known as PRSP (pregnancy-related serine protease), is a 453 amino acid secreted protein that contains one PDZ domain, one Kazal-like domain and one IGFBP N-terminal domain. Widely expressed with particularly high expression in ovary, heart, placenta and bladder, HtrA3 functions as a probable serine protease that is thought to play an important role in placental development. HtrA3 is downregulated in ovarian tumors, suggesting an alternative role in tumor suppression. HtrA3 exists as two alternatively spliced isoforms, designated short and long. The gene encoding HtrA3 maps to human chromosome 4, which encodes nearly 6% of the human genome and has the largest gene deserts (regions of the genome with no protein encoding genes) of all of the human chromosomes. Protein function: Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans. May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization (PubMed:21321049, PubMed:22229724). [The UniProt Consortium]
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