Browse anti-prokaryotic immune system genes

The list of 41 experimentally verified APIS genes

APIS genes APIS families Immune system CLAN ID Phages/MGEs References Description
Apyc1 APIS001 pyrimidine cyclase system for antiphage resistance (Pycsar) CLAN030 Bsp38 of Bacillus subtilis PMID:35395152 SBSphiJ Apyc1 efficiently hydrolyses a wide range of cyclic mononucleotides; 273 Acb1 and 107 Apyc1 phage proteins were identified.
vs.4 APIS002 cyclic oligonucleotide-based antiphage signaling system (CBASS) CLAN018 T4 of E. coli PMID:36848932 Vs.4 antagonized cGAS signaling by binding tightly to cGAMP (dissociation constant of approximately 30 nM) and sequestering it; Bioinformatic analyses identified 198 homologues of Vs.4 in diverse phages; belongs to PHROG 717.
ArdA APIS003 restriction-modification (RM) CLAN004 plasmid pKM101 of E. coli PMID:2989658 DNA mimetics, i.e. structurally and electrostatically imitate the B-form of DNA and thus function as competitive inhibitors of restriction enzymes.
Acb2 APIS004 cyclic oligonucleotide-based antiphage signaling system (CBASS) CLAN018 PaMx33 of Pseudomonas aeruginosa PMID:36750095 Anti-CBASS protein ("Acb2") that forms a hexamer with three 3',3'-cGAMP molecules and reduces phospholipase activity.
Gad1 APIS005 Gabija CLAN001 phi3T of B. subtilis Yirmiya et al., 2023 Antine et al., 2023 Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage.
abc1 APIS006 RecBCD CLAN014 Salmonella phage S149 Silas et al., 2023 Trigger programmed cell death (PCD) by P4 prophage.
KlcA APIS007 restriction-modification (RM) CLAN003 IncP-1b plasmid of Bordetella pertussis PMID:20007596 ArdB and KlcA act as anti-restriction proteins and inhibit the four main families of Type I RM systems in vivo.
Gad2 APIS008 Gabija CLAN002 SPbetaL7 of B. subtilis Yirmiya et al., 2023 Alphafold2 predicted that Gad2 is an enzyme with a nucleotidyltransferase protein domain, suggesting that it inhibits Gabija via a mechanism of action different than Gad1.
Ral APIS009 restriction-modification (RM) CLAN013 Lambda of E. coli PMID:3023633 Ral of phage λ can activate the activity of the MTase and thereby accelerate protection of the phage DNA.
Ocr APIS010 restriction-modification (RM);bacteriophage exclusion (BREX) CLAN020 T7 of E. coli PMID:32338761 329108 12235377 11804597 Ocr physically associates with BrxX methyltransferase to neutralizes their ability to both methylate and exclude incoming phage DNA. Ocr structurally mimics the DNA phosphate backbone and interacts directly with EcoKI (both the MTase and REase domain of this type I R–M enzyme), thereby interfering with the activity of this system.
gp4.5 APIS011 toxin-antitoxin (TA) CLAN023 T7 of E. coli PMID:23478446 Protein gp4.5 allows T7 to block Lon (protease) from degrading antitoxins (the SanTA system in E. coli), including SanaA, thereby preventing liberation of SanaT. However, beyond a possible interaction between gp4.5 and Lon in uninfected cells, this speculative model remains untested.
tifA APIS012 toxin-antitoxin (TA) CLAN022 T4 of E. coli PMID:35924892 Original gene 61.4, experimentally evolved T4 phage to overcome a phage-defensive toxin-antitoxin system (toxIN) in E. coli. Through recombination, T4 rapidly acquires segmental amplifications of a previously uncharacterized gene, now named tifA, encoding an inhibitor of the toxin, ToxN.
Dmd APIS013 toxin-antitoxin (TA) CLAN027 T4 of E. coli PMID:22403819 T4 produces Dmd, an antitoxin that inhibits E. coli RnlA and LsoA toxins. Dmd differs from the RnlB or LsoB antitoxins, suggesting it evolved independently, which is highlighted by its different toxin neutralization mechanism.
PinA APIS014 toxin-antitoxin (TA) CLAN026 T4 of E. coli PMID:9417110 PinA encoded by T4 was discovered 20 years ago, it could help T4 block TA defense systems that require Lon, but in vivo function for pinA has not been reported.
IpII APIS015 restriction-modification (RM) CLAN010 T4 of E. coli Silas et al., 2023 T4 internal-protein, a T2-restricting defense system was disabled by IpII. IpII restored T2 and T6 plaquing but did not further enhance T4 infection.
Acb1 APIS016 cyclic oligonucleotide-based antiphage signaling system (CBASS) CLAN019 T4 of E. coli PMID:35395152 Acb1 rapidly degrades the CBASS signals 3′3′-cGAMP, cUA and cAAA, but does not cleave cGG.
Alt APIS017 toxin-antitoxin (TA) CLAN024 T4 of E. coli PMID:26395283 T4 protein Alt (an ADP-ribosyltransferase) is injected with phage DNA, which chemically modifies the MazF toxin. ADP-ribosylated MazF has reduced cleavage activity, enabling the survival of the phage.
Arn APIS018 restriction-modification (RM) CLAN011 T4 of E. coli PMID:25118281 T4 phage protein Arn (Anti restriction nuclease) was identified as an inhibitor of the restriction enzyme McrBC.
gnarl2 APIS019 O-antigen-based barrier CLAN035 Escherichia phage Mu Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
Abc2 APIS020 RecBCD CLAN016 Salmonella phage P22 PMID:10669596 36533901 Bacteriophage P22 Abc2 protein binds to the RecBCD enzyme from E. coli to promote phage growth and recombination; the RecBCD-Abc2 structure shows that Abc2 binds to the Chi-recognition domains of the RecC subunit in a position that might enable it to mediate the loading of phage recombinases onto its single-stranded DNA products.
SieA APIS021 restriction-modification (RM) CLAN005 Salmonella phage P22 Silas et al., 2023 Superinfection exclusion.
adfA APIS022 toxin-antitoxin (TA) CLAN025 RB69 of E. coli PMID:35725776 Gene adfA(gp61.2) is encoded as a DarT (TA system) inhibitor.
gp5.9 APIS023 RecBCD CLAN017 T7 of E. coli PMID:36533901 Gp5.9 completely inhibits RecBCD by preventing it from binding to DNA. The RecBCD-gp5.9 structure shows that gp5.9 acts by substrate mimicry, binding predominantly to the RecB arm domain and competing sterically for the DNA binding site.
Tad1 APIS024 Thoeris CLAN031 SBSphiJ7 of B. subtilis PMID:36174646 Tad1 proteins are not an enzymes, but are 'sponges' that bind and sequester the immune signaling molecule (cyclic ADP-ribose or gcADPR) produced by TIR-domain proteins, thus decoupling phage sensing from immune effector activation and rendering Thoeris inactive.
Had1 APIS025 Hachiman CLAN037 SBSphiJ4 of B. subtilis Yirmiya et al., 2023 Had1 (Hachiman anti-defense 1) is a Hachiman-inhibiting family of phage proteins. The mechanism of Hachiman defense is unknown.
orf126 APIS026 broad-spectrum counter-defense CLAN029 Salmonella phage SPFM20 Silas et al., 2023 Broad-spectrum counter-defense.
DSAD1 APIS027 defence-associated sirtuin (DSR) CLAN038 SPbeta phages of B. subtilis PMID:36192536 DSAD1 is a phage anti-DSR2 protein that binds and inhibits Defence-associated sirtuins (DSR2). In bacteria, N-terminal sirtuin (SIR2) domains within DSR2 were shown to participate in defence systems including prokaryotic argonautes (pAgo), Thoeris, AVAST, defence-associated sirtuin (DSR), etc.
Tad2 APIS029 Thoeris CLAN031 Bacillus phage SPO1 Yirmiya et al., 2023 Tad2 is a "sponge" that sequesters the immune signaling molecules produced by Thoeris TIR-domain proteins in response to phage.
DarB APIS030 restriction-modification (RM) CLAN009 P1 of E. coli PMID:3029954 Bind to phage DNA, thereby masking type I R–M recognition sites and preventing degradation of phage DNA.
DarA APIS031 restriction-modification (RM) CLAN006 P1 of E. coli PMID:3029954 Bind to phage DNA, thereby masking type I R–M recognition sites and preventing degradation of phage DNA.
Cor APIS032 superinfection exclusion CLAN032 Enterobacteria phage phi80 PMID:15518820 Superinfection exclusion, inactivates FhuA receptor.
Lar APIS033 restriction-modification (RM) CLAN007 Escherichia phage vB_EcoP_24B PMID:7476171 Lar is functionally similar to RaI, is able to alleviate restriction and enhance modification by EcoKI. And the nucleotide sequences of their genes share 47% identity, indicating a common origin.
gnarl1 APIS034 O-antigen-based barrier CLAN036 Klebsiella phage vB_KpnM_KpV79 Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
orf148 APIS035 broad-spectrum counter-defense CLAN028 Escherichia phage OSYSP Silas et al., 2023 Broad-spectrum counter-defense.
gnarl3 APIS036 O-antigen-based barrier CLAN034 Escherichia phage Mangalitsa Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
IpI APIS090 restriction-modification (RM) CLAN008 T4 of E. coli PMID:17188297 18037438 Restriction endonuclease inhibitor IpI blocks the ancestral two-component type IV R-M system and represents a third generation bacteriophage defense against restriction nucleases of the Gmr type.
HOS17_gp01 APIS091 restriction-modification (RM);bacteriophage exclusion (BREX) CLAN015 T3 of E. coli Andriianov et al., 2023 T3 encodes a SAMase that circumvents the SAM-dependent Type I R-M defence of the host E. coli through cleavage of S-adenosyl-methionine (SAM). SAMase also allows T3 to evade BREX defence.
Gam APIS092 RecBCD CLAN021 Lambda of E. coli PMID:24086157 The protein Gam inhibits the host RecBCD exonuclease activity thus allowing efficient rolling-circle replication.
ArdB ArdB restriction-modification (RM) CLAN003 plasmid pKM101 of E. coli PMID:8393008 Like ArdA, ArdB efficiently inhibits restriction by members of the three known families of type I systems of E. coli and only slightly affects the type II enzyme, EcoRI.
gp54 gp54 superinfection exclusion CLAN033 Mycobacterium phage Tweety PMID:28067906 A tetrapeptide repeat protein that acts as a highly effective counter-defense system by preventing activation of (p)ppGpp synthesis encoded by Phrann prophage-mediated defense system.
Stp Stp restriction-modification (RM) CLAN012 T4 of E. coli PMID:7791212 Stp has been implicated with activation of the anticodon nuclease and inhibition of EcoprrI restriction.