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Browse anti-prokaryotic immune system genes

The list of 84 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) CLAN001 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) CLAN002 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) CLAN003 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) CLAN002 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 CLAN004 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 CLAN005 Salmonella phage S149 Silas et al., 2023 Trigger programmed cell death (PCD) by P4 prophage.
KlcA APIS007 restriction-modification (RM) CLAN006 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 CLAN007 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) CLAN008 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) CLAN009 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) CLAN010 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) CLAN011 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) CLAN012 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) CLAN013 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) CLAN014 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) CLAN015 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) CLAN016 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) CLAN017 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 CLAN018 Escherichia phage Mu Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
Abc2 APIS020 RecBCD CLAN019 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) CLAN020 Salmonella phage P22 Silas et al., 2023 Superinfection exclusion.
adfA APIS022 toxin-antitoxin (TA) CLAN021 RB69 of E. coli PMID:35725776 Gene adfA(gp61.2) is encoded as a DarT (TA system) inhibitor.
gp5.9 APIS023 RecBCD CLAN022 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 CLAN023 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 CLAN024 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 CLAN025 Salmonella phage SPFM20 Silas et al., 2023 Broad-spectrum counter-defense.
DSAD1 APIS027 defence-associated sirtuin (DSR) CLAN026 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 CLAN023 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) CLAN027 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) CLAN028 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 CLAN029 Enterobacteria phage phi80 PMID:15518820 Superinfection exclusion, inactivates FhuA receptor.
Lar APIS033 restriction-modification (RM) CLAN030 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 CLAN031 Klebsiella phage vB_KpnM_KpV79 Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
orf148 APIS035 broad-spectrum counter-defense CLAN032 Escherichia phage OSYSP Silas et al., 2023 Broad-spectrum counter-defense.
gnarl3 APIS036 O-antigen-based barrier CLAN033 Escherichia phage Mangalitsa Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
IpI APIS090 restriction-modification (RM) CLAN034 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) CLAN035 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 CLAN036 Lambda of E. coli PMID:24086157 The protein Gam inhibits the host RecBCD exonuclease activity thus allowing efficient rolling-circle replication.
Rad APIS094 Retron CLAN037 Escherichia phage SP15 Azam et al., 2023 Rad inhibited retron function by degrading noncoding RNA, the precursor of msDNA.
ugi APIS101 DNA repair CLAN040 Bacillus phage AR9 PMID: 6776115 Uracil-DNA-glycosylase inhibitor.
NTases APIS103 CBASS, Pycsar and CRISPR–Cas (type III) CLAN042 Bacillus phage BCP1 PMID:36952342 A family of bacteriophage nucleotidyltransferases (NTases) that synthesize competitor cyclic dinucleotide (CDN) ligands and inhibit TIR NADase effectors activated via a linked STING CDN sensor domain (TIR-STING). 
narp2_nampt APIS104 NAD+ reconstitution pathway (NARP) CLAN043 Vibrio phage KVP40 Osterman et al., 2024 Nicotinamide phosphoribosyltransferase activity (Nampt), capable of producing NMN from PRPP and nicotinamide.
dam APIS107 restriction-modification (RM) CLAN045 Escherichia phage T4 PMID:6307815 DNA adenine methylases methylate adenine residues in specific sequences, the methylation site of the host Escherichia coli dam+ methylase. Methylation protects the site against cleavage by the MboI restriction nuclease.
ardc APIS108 restriction-modification (RM) CLAN046 Enterobacterales PMID:10686096 This anti-restriction protein is able in vitro to protect the single-stranded DNA against the activity of type II restriction endonuclease HhaI.
mom APIS111 restriction-modification (RM) CLAN047 Escherichia phage Mu PMID:2934296 Methylcarbamoylase for DNA modification.
antiDnd_p0020 APIS113 Dnd CLAN048 Vibrio phage 44E38.1 PMID:35760840 Two genes (p0020 and p0021) provide resistance to the Dnd system (anti-Dnd), p0020 encodes a protein with a phosphoadenosine phosphosulphate reductase (PAPS) domain and a DNA N-6-adenine-methyltransferase (Dam) domain.
mga47 APIS117 toxin-antitoxin (TA) CLAN050 Escherichia phage SECphi18 PMID:35725776 DNA polymerase
Ulx APIS119 restriction-modification (RM) CLAN051 Escherichia phage P1 PMID:28509398 Ulx is a protein included in the P1 antirestriction system. It acts as a chaperone or packaging factor to increase the amount of DarB incorporated into the virion.
U56 APIS125 toxin-antitoxin (TA) CLAN052 Escherichia phage Ukendt PMID:38788717 Retron-Eco1 inhibitor
Lidtsur-6 APIS129 AVAST (Antiviral STAND) CLAN053 Escherichia phage Lidtsur PMID:35951700 Lidtsur-6, Lidtsur-17 and Forsur-7 were active in phage plaque assays and restored phage propagation on Avs-containing E. coli.
RacC APIS130 Retron CLAN054 prophage of Escherichia coli str. K-12 substr. MG1655 PMID:35850148 RacC is a Rac prophage gene, function as retron TA blocker. It directly blocks RcaT toxicity, inhibit the toxin of abortive infection systems.
vcrx091 APIS131 CRISPR-Cas evasion by DNA repair CLAN055 Vibrio cholerae PMID:32556263 CRISPR–Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats
MpaR APIS132 SOS response CLAN041 prophage of Listeria monocytogenes 10403S PMID:31754112 MpaR plays a critical role in the de-repression (induction) of the two phage elements and is sufficient for ϕ10403S induction.
vcrx092 APIS133 CRISPR-Cas evasion by DNA repair CLAN056 Vibrio cholerae PMID:32556263 CRISPR–Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats
hia5 APIS136 restriction-modification (RM) CLAN045 Haemophilus influenzae PMID:22102579 hin1523, nma1821 and hia5 are all DNA adenine N6-methyltransferases. Plasmid DNA overexpressing these novel DNA methyltransferases was resistant to cleavage by many restriction enzymes sensitive to adenine methylation.
hin1523 APIS136 restriction-modification (RM) CLAN045 Haemophilus influenzae Rd KW20 PMID:22102579 hin1523, nma1821 and hia5 are all DNA adenine N6-methyltransferases. Plasmid DNA overexpressing these novel DNA methyltransferases was resistant to cleavage by many restriction enzymes sensitive to adenine methylation.
nma1821 APIS136 restriction-modification (RM) CLAN045 Neisseria meningitidis PMID:22102579 hin1523, nma1821 and hia5 are all DNA adenine N6-methyltransferases. Plasmid DNA overexpressing these novel DNA methyltransferases was resistant to cleavage by many restriction enzymes sensitive to adenine methylation.
Hdf APIS143 restriction-modification (RM) CLAN028 Escherichia phage P1 PMID:28509398 A key member in the P1 Dar antirestriction system. The absence of either Hdf or DarA results in failure to incorporate any of the other antirestriction proteins.
OrbA APIS148 bacteriophage exclusion (BREX) CLAN058 Vibrio phage ICP1 PMID:34326207 Clinical phage ICP1 overcomes cocirculating SXT ICEs through acquisition of epigenetic RM as well as an anti-BREX protein, OrbA.
Atd1 APIS150 TIR-STING CLAN044 Pseudoalteromonas phage PH357 PMID:36952342 Functional screen identifies Atd1, a phage MazG-like suppressor of TIR-STING cell suicide
dmt APIS152 restriction-modification (RM) CLAN045 Escherichia phage P1 PMID:14715260 DNA methyltransferase (M.EcoP1I) encoded by prophage P1, may protect the phage genome from restriction by type III restriction enzymes and thus could be considered as an anti-restriction system.
antiDnd_p0021 APIS153 Dnd CLAN059 Vibrio phage 44E38.1 PMID:35760840 Two genes (p0020 and p0021) provide resistance to the Dnd system (anti-Dnd), p0021 encodes a protein of unknown function.
narp1_adps APIS160 NAD+ reconstitution pathway (NARP) CLAN057 Escherichia phage JohannRWettstein Osterman et al., 2024 Phage enzyme ADPR-PP synthetase (Adps).
Lidtsur-17 APIS164 AVAST (Antiviral STAND) CLAN061 Escherichia phage Lidtsur PMID:35951700 Lidtsur-17 inhibits SeAvs3 nuclease activity in vitro.
Ddra APIS165 restriction-modification (RM) CLAN062 Escherichia phage P1 PMID:28509398 It's included in the P1 restriction system. The proteins Hdf, DarA and DdrA are required for the protection of phage DNA from restriction by the EcoA Type I R-M system.
vcrx089 APIS166 restriction-modification (RM) CLAN039 Vibrio cholerae PMID:32556263 vcrx089 and vcrx090 promote resistance against type I restriction-modification.
narp2_nmnat APIS170 NAD+ reconstitution pathway (NARP) CLAN049 Vibrio phage KVP40 Osterman et al., 2024 Nicotinamide mononucleotide adenylyltransferase (Nmnat), capable of generating NAD+ by conjugating AMP to NMN.
AriS APIS178 SOS response CLAN060 prophage of Listeria monocytogenes 10403S PMID:35443160 LMRG_02920 (AriS) encodes in prophage L. monocytogenes strain 10403S. It acts as a RecA inhibitor and inhibits the bacterial SOS response.
Ddrb APIS179 restriction-modification (RM) CLAN063 Escherichia phage P1 PMID:28509398 It's included in the P1 restriction system. The presence of DdrB results in reduced antirestriction activity, presumably by negatively affecting DarB but the mechanism is not known.
psib APIS180 SOS response CLAN064 Escherichia coli PMID:19818715 PsiB protein works as an SOS inhibitor that binds to RecA to inhibit its activities.
vcrx093 APIS185 CRISPR-Cas evasion by DNA repair CLAN038 Vibrio cholerae PMID:32556263 CRISPR–Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats
Forsur-7 APIS193 AVAST (Antiviral STAND) CLAN053 Escherichia phage forsur PMID:35951700 Forsur-7 inhibits SeAvs3 nuclease activity in vitro to a lesser degree.
AdfN APIS195 toxin-antitoxin (TA) CLAN065 Escherichia phage T4 PMID:39026772 Anti-DarT factor NADAR (AdfN), removes ADP-ribose modifications from phage DNA during infection thereby enabling replication in DarTG1-containing bacteria. AdfN, like DarG1, is in the NADAR superfamily of ADP-ribosylglycohydrolases.
narp1_namat APIS197 NAD+ reconstitution pathway (NARP) CLAN043 Escherichia phage JohannRWettstein Osterman et al., 2024 Phage enzyme Nicotinamide ADPR-transferase (Namat)
ArdB ArdB restriction-modification (RM) CLAN006 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.
ardk ardk restriction-modification (RM) CLAN068 Plasmid pKM101 PMID: 8393008 ArdK and ArdR likely serve as ardKR-dependent regulatory system that controls the expression of ArdA and ArdB.
ardr ardr restriction-modification (RM) CLAN069 Plasmid pKM101 PMID: 8393008 ArdK and ArdR likely serve as ardKR-dependent regulatory system that controls the expression of ArdA and ArdB.
ardu ardu restriction-modification (RM) CLAN003 Shuttle vector pI3 PMID:10966401 The gene was from contructed E. coli-D. radiodurans shuttle vector,pI3, and trikingly similar to the known plasmid-encoded antirestriction proteins like ArdA.
gp54 gp54 superinfection exclusion CLAN070 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.
pCARD pCARD Gasdermin CLAN066 Acinetobacter phage 133 PMID:37398489 A phage CARD-only (pCARD) protein with a predicted CARD-like structure that can inhibit the CARD-containing bacterial gasdermin system.
psia psia SOS response CLAN071 Enterobacteriaceae Samuel and Burstein, 2023 SOS-inhibitor.
Stp Stp restriction-modification (RM) CLAN072 T4 of E. coli PMID:7791212 Stp has been implicated with activation of the anticodon nuclease and inhibition of EcoprrI restriction.
vcrx090 vcrx090 restriction-modification (RM) CLAN073 Vibrio cholerae PMID:32556263 vcrx089 and vcrx090 promote resistance against type I restriction-modification.
ADG.17 ADG.17 toxin-antitoxin (TA) CLAN067 Sulfolobus monocaudavirus SMV1 PMID:38698035 ADG.17 and its homologs in archaea viruses act as antitoxins to inhibit host toxin Doc. It's the first example of an inhibitor of an archaeal toxin-antitoxin immune system.