The SEFIR defense system is composed of a single bacterial SEFIR (bSEFIR)-domain protein. bSEFIR-domain genes were identified in bacterial genomes, were shown to be enriched in defense islands and the activity of the defense system was first experimentally validated in *Bacillus sp.* NIO-1130 against phage phi29 [1].
The SEFIR defense system is composed of a single bacterial SEFIR (bSEFIR)-domain protein. bSEFIR-domain genes were identified in bacterial genomes, were shown to be enriched in defense islands and the activity of the defense system was first experimentally validated in *Bacillus sp.* NIO-1130 against phage Phi29 :ref{doi=10.1016/j.chom.2022.09.017}.
Bacterial SEFIR domains were named after their eukaryotic homologs which were already known to be part of several eukayrotic immune proteins (e.g. SEFs and Interleukin-17 Receptors):ref{doi=10.1016/S0968-0004(03)00067-7}.
Homologs of SEFIR domain proteins were also found in archaeal species : _Methanosarcina barkeri_ and _Methanosarcina mazei_ :ref{doi=10.1016/j.chom.2022.09.017}.
Bacterial SEFIR domains were named after their eukaryotic homologs which were already known to be part of several eukayrotic immune proteins (e.g. SEFs and Interleukin-17 Receptors) [2].
## Molecular mechanism
SEFIR was shown to protect against phage infection through an abortive infection mechanism *via* NAD+ depletion. This is similar to what can be observed in other defense systems containing a TIR domain which shares homology with the SEFIR domain (in eukaryotes, both domains are part of the STIR super family) [1].
SEFIR was shown to protect against phage infection through an abortive infection mechanism *via* NAD+ depletion. This is similar to what can be observed in other defense systems containing a TIR domain which shares homology with the SEFIR domain (in eukaryotes, both domains are part of the STIR super family) :ref{doi=10.1016/j.chom.2022.09.017}.
[1] Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).
[2] Novatchkova, M., Leibbrandt, A., Werzowa, J., Neubüser, A., & Eisenhaber, F. (2003). The STIR-domain superfamily in signal transduction, development and immunity. _Trends in biochemical sciences_, _28_(5), 226-229.
