{PDOC00987} {PS01282; BIR_REPEAT_1} {PS50143; BIR_REPEAT_2} {BEGIN} ************************************ * 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 ). The structure consists of three short alpha-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 ), are likely to contain a C-terminal region that form an alpha-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. -Consensus pattern: [HKEPILVY]-x(2)-R-x(3,7)-[FYW]-x(11,14)-[STAN]-G-[LMF]-x- [FYHDA]-x(4)-[DESL]-x(2,3)-C-x(2)-C-x(6)-[WA]-x(9)-H-x(4)- [PRSD]-x-C-x(2)-[LIVMA] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: November 2011 / Text revised. [ 1] Birnbaum M.J., Clem R.J., Miller L.K. "An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs." J. Virol. 68:2521-2528(1994). PubMed=8139034 [ 2] Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., Farahani R., McLean M., Ikeda J.E., MacKenzie A., Korneluk R.G. "Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes." Nature 379:349-353(1996). PubMed=8552191 [ 3] Hinds M.G., Norton R.S., Vaux D.L., Day C.L. "Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat." Nat. Struct. Biol. 6:648-651(1999). PubMed=10404221; DOI=10.1038/10701 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}