8.A.217. The Apoptosis Cell Death Regulator (ACDR) Family A huge protein machine regulates cell death in mammals and other animals. In humans, it consists of IAPs, inhibitors of apoptosis, that contain at least one (and often more) baculoviral IAP repeats (BIRs). One such IAP is BIRC6, the largest IAP of 4857 aas, with only one BIR repeat, although this protein exists as a dimer of about 9,700 aas. It controls cell fate. Then there are Second Mitochondrial-derived Activators of Caspases (SMACs) with four amino acid motifs that bind to BIR repeats in IAPs (inhibitors of apoptosis). HTRA2 is an apoptotic protease as well as a ubiquitin ligase for caspases 3, 7 and 9. Caspases are thiol proteases involved in different programmed cell death processes, such as apoptosis, pyroptosis and granzyme-mediated programmed cell death, by proteolytically cleaving target proteins (Fernandes-Alnemri et al. 1995). Caspase3 = CPP3 of 277 aas (P42574); Caspase7 = MCH3 of 303 aas (P55210); Caspase9 = MCH6 of 416 aas (P55211), and HTRA27 = Omi of 458 aas (O43464).
References:
Fernandes-Alnemri, T., A. Takahashi, R. Armstrong, J. Krebs, L. Fritz, K.J. Tomaselli, L. Wang, Z. Yu, C.M. Croce, and G. Salveson. (1995). Mch3, a novel human apoptotic cysteine protease highly related to CPP32. Cancer Res 55: 6045-6052.
Examples:
TC#	Name	Organismal Type	Example
8.A.217.1.1	The massive protein machine that regulates cell death/apoptosis, BIRC6 is a subunit of 4857 aas with one BIR domain. The complex regulates several caspases (caspase3, caspase7 and caspase9 as well as Omi; see below), BIRC6, SMAC, several IAPs (inhibitors of apoptosis), and ACDR (Apoptosis Cell Death Regulator).		Regulator of Cell Death and Apoptosis BIRC6, 4857 aas, Q9NR09 Caspase3, CPP3, 277 aas, P42574 Caspase7, CPP7, 303 aas, P55210 Caspase9, CPP9, 416 aas, P55211 HTRA2 apoptosis serine protease, 458 aas, O43464 SMAC (Second Mitochondria-derived Activator of Caspases) IAPs (Inhibitors of Apoptosis) - contain 1 - n baculoviral IAP repeats (BIRs)