PROSITE documentation PDOC00987

BIR repeat signature and profile

The 'baculovirus inhibitior of apoptosis protein repeat' (BIR) [1,2] is a domain of about 70 residues arranged in tandem repeats separated by a variable length linker, that seems to confer cell death-preventing activity. It is found in proteins belonging to the IAP (inhibitor of apoptosis proteins) family. The critical motifs required for anti-apoptotic activity of IAP proteins are the BIRs. All IAP proteins contain from one to three BIRs, and all known interactions between IAPs and other proteins are mediated by one or more BIRs [3].

The BIR domain has a fold that is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues (see <PDB:1QBH>). The structure consists of three short α-helices and turns with the zinc packed in an unusually hydrophobic environment created by residues that are highly conserved among all BIRs. A subclass of repeats, comprising those at the C-terminus of a series of BIR repeats from IAP proteins bearing RING finger domains (see <PDOC00449>), are likely to contain a C-terminal region that form an α-helix [3].

Proteins that are known to contain this domain are listed below.

• Baculoviruses apoptosis inhibitors (IAPs).
• Mammalian apoptosis inhibitors 1 and 2 (IAP1 and IAP2).
• Mammalian X-linked inhibitor of apoptosis protein (X-linked IAP).
• Chicken IAP (ITA).
• Human neuronal apoptosis inhibitory protein (NAIP).
• Drosophila apoptosis inhibitors 1 and 2 (Iap1 and Iap2).
• African Swine Fever Virus (ASFV) protein p27.

BIR contains a number of perfectly conserved residues including an histidine and three cysteines. The signature pattern for BIR spans the total length of the repeat. We also developed a profile that spans the whole repeat.