{PDOC52055} {PS52055; UBL_BIL} {BEGIN} ************************************************************ * Bacterial ISG15-like (Bil) ubiquitin-like domain profile * ************************************************************ Ubiquitylation is a widespread posttranslational modification that controls most of eukaryotic cell biology. The process relies on a cascade of E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes, and E3 ubiquitin ligases to conjugate the small protein ubiquitin onto substrates. Ubiquitination can be reversed by deubiquitinases (DUBs), which are peptidases capable of removing ubiquitin from target molecule [1,2]. Several immune pathways in humans conjugate ubiquitin-like proteins to virus and host molecules as a means of antiviral defense. Interferon-stimulated gene 15 (ISG15) is one of the most strongly and rapidly induced genes as part of the type I interferon antiviral response. ISG15 is a ubiquitin-like protein composed of two fused ubiquitin-like domains, which is involved in protecting human cells against a variety of viruses such as influenza A and HIV-1. This protein was shown to be conjugated by dedicated interferon-induced ubiquitin- conjugating enzymes (E1, E2, and E3) onto many viral and host proteins during infection [2,3]. Like eukaryotes, bacteria can also be infected by viruses (phages), against which bacteria have evolved a plethora of immune defense strategies. One antiphage defense system in bacteria, comprises a ubiquitin-like protein, ubiquitin-conjugating enzymes E1 and E2, and a deubiquitinase. Owing to its double-UBL domain and role in antiviral defense, the system was coined "Bil" (bacterial ISG15-like), and is composed of BilA/B/C/D encoding UBL, E2, DUB, and E1 modules, respectively. The Bil system covalently conjugates its Ubl protein to the phage central tail fibre (CTF), an essential structural component of the phage tail tip that is crucial for both tail assembly and host recognition. Conjugation of the Ubl to the CTF inhibits tail assembly, leading to the production of non-infective, tailless phages [1,2]. The Bil system is a representative of a large family of defense systems encoding E1, E2 and Ubl proteins. In some of these systems, the Ubl contains a single ubiquitin-like domain (instead of the two fused domains in the Bil system), and in some cases, the gene with the DUB domain is missing [2]. The profile we developed covers the entire Bil-type UBL domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: January 2025 / First entry. [ 1] Pruneda J.N., Randow F. "Ubiquitylation: Sword and shield in the bacterial arsenal." Mol. Cell. 84:3378-3380(2024). PubMed=39303679; DOI=10.1016/j.molcel.2024.08.034 [ 2] Hoer J., Wolf S.G., Sorek R. "Bacteria conjugate ubiquitin-like proteins to interfere with phage assembly." Nature 631:850-856(2024). PubMed=39020165; DOI=10.1038/s41586-024-07616-5 [ 3] Millman A., Melamed S., Leavitt A., Doron S., Bernheim A., Hoer J., Garb J., Bechon N., Brandis A., Lopatina A., Ofir G., Hochhauser D., Stokar-Avihail A., Tal N., Sharir S., Voichek M., Erez Z., Ferrer J.L.M., Dar D., Kacen A., Amitai G., Sorek R. "An expanded arsenal of immune systems that protect bacteria from phages." Cell. Host. Microbe. 30:1556-1569.e5(2022). PubMed=36302390; DOI=10.1016/j.chom.2022.09.017 -------------------------------------------------------------------------------- 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}