Structure and evolution of BIRPs. (a) Domain structures of BIRPs in mammals (humans), insects, nematodes and yeast. The length of each protein (in amino acids) is shown on the right. IAPs have type 1 BIR domains (dark blue), whereas type 2 BIR domains (light blue) are found in Survivin-like BIRPs. (b) The evolutionary relationship of BIR domains. A phylogenetic tree was generated using the parsimony option of the PHYLIP Phylogeny Inference Package (version 3.5c) , from BIR domains aligned by the Clustal W1.7 program. The accession numbers and regions used in the analysis are shown in Table 2. Default settings were used; the order of the sequences was jumbled 10 times and the degree of certainty for each node (the bootstrap value, shown on the Figure) was calculated from 100 random replicates. All bootstrap values greater than 50 and selected others are shown. The values for placement of ML-IAP with NAIP BIR3 and BIR2 domains are very low, and trees calculated using distance methods placed ML-IAP BIR with the BIR3 domains of XIAP, cIAP-1 and cIAP-2. Also, note that the alignment used to generate this tree does not include the carboxy-terminal α-helical extension that is conserved between the BIR3 domains of XIAP, cIAP-1, cIAP-2 and ML-IAP but not NAIP. (c) Two types of BIR domain. An alignment of a selection of BIR domains illustrates the difference between BIR domains present within classical IAPs (top four sequences) and within other BIRPs (bottom four). Aligned regions are as given in Table 2. Amino acids that are conserved in all BIR domains are highlighted. Type 1 BIR domains are approximately 70 amino acids long, whereas type 2 BIR domains are longer.