| Modification Notes |
APIP (Apaf-1-interacting protein), also known as APIP2, is a member of the aldolase class II family and has a highly conserved C-terminal from C. elegans to humans. It is ubiquitously expressed, with high expression levels in heart, kidney and skeletal muscle. Alternative splicing produces two isoforms of APIP. Isoform 1 is the full length, 242 amino acid protein; isoform 2 is missing residues 1-38 and contains a distinct sequence for amino acids 39-53. APIP plays an important role in preventing muscle ischemic damage. It suppresses hypoxia-induced cell death by inducing the activation of Akt and ERK 1/2, which are responsible for inhibition of caspase-9 via phosphorylation, and competing with caspase-9 to bind the caspase recruitment domain (CARD) of Apaf-1. Through these mechanisms, APIP negatively regulates the activation of caspase-9 and Apaf-1-mediated cell death. |