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Beschreibung

"Protein SET (UniProt Q01105, also known as HLA-DR-associated protein II, IGAAD, Inhibitor of granzyme A-activated DNase, PHAPII, I-2PP2A, Phosphatase 2A inhibitor I2PP2A, TAF-I, Template-activating factor I) is encoded by the SET gene (Gene ID 6418) in human. Protein SET (patient ""SE translocation"") adopted its name when it was originally identified in a leukemia study in 1992. SET interacts with signaling pathways that promote normal cell growth and proliferation, as well as tumorigenesis and metastasis. SET protein inhibits PP2A by enhancing lyase activity of P450c17, a substrate for PP2A when it is Ser- and Thr-phosphorylated. Alternative splicings result in multiple SET isoforms, including SET-alpha (TAF-I alpha), SET-beta (TAF-I beta), and a shorter spliced Set-beta isoform without the nuclear localization signal (NLS). Set-beta functions have been described both in the nucleus and cytoplasm. The presence of a nuclear localization signal (NLS) and phosphorylation govern Set-beta isoforms cellular localization. Proteolytic cleavage of Set-beta at Lys176 by granzyme A or at Asn-175 by asparagine endopeptidase results in the release of GzmA-activated DNase (GAAD) from a multiprotein complex. Uninhibited in the absence of the full-length Set-beta, GAAD causes cell death by its DNA-nicking activity."