Browse anti-prokaryotic immune system genes

The list of 149 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) CLAN008 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) CLAN056 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) CLAN005 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) CLAN036 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 CLAN009 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 CLAN037 Salmonella phage S149 Silas et al., 2023 Trigger programmed cell death (PCD) by P4 prophage.
KlcA APIS007 restriction-modification (RM) CLAN011 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 CLAN023 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) CLAN057 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) CLAN017 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) CLAN024 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) CLAN038 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) CLAN058 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) CLAN059 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) CLAN060 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) CLAN061 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) CLAN062 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) CLAN063 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 CLAN064 Escherichia phage Mu Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
Abc2 APIS020 RecBCD CLAN065 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) CLAN039 Salmonella phage P22 Silas et al., 2023 Superinfection exclusion.
adfA APIS022 toxin-antitoxin (TA) CLAN066 RB69 of E. coli PMID:35725776 Gene adfA(gp61.2) is encoded as a DarT (TA system) inhibitor.
gp5.9 APIS023 RecBCD CLAN067 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 CLAN001 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 CLAN068 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 CLAN069 Salmonella phage SPFM20 Silas et al., 2023 Broad-spectrum counter-defense.
DSAD1 APIS027 defence-associated sirtuin (DSR) CLAN070 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 CLAN001 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) CLAN071 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) CLAN040 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 CLAN072 Enterobacteria phage phi80 PMID:15518820 Superinfection exclusion, inactivates FhuA receptor.
Lar APIS033 restriction-modification (RM) CLAN041 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 CLAN073 Klebsiella phage vB_KpnM_KpV79 Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
orf148 APIS035 broad-spectrum counter-defense CLAN018 Escherichia phage OSYSP Silas et al., 2023 Broad-spectrum counter-defense.
gnarl3 APIS036 O-antigen-based barrier CLAN074 Escherichia phage Mangalitsa Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
IpI APIS090 restriction-modification (RM) CLAN075 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) CLAN042 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 CLAN076 Lambda of E. coli PMID:24086157 The protein Gam inhibits the host RecBCD exonuclease activity thus allowing efficient rolling-circle replication.
Rad APIS094 Retron CLAN025 Escherichia phage SP15 Azam et al., 2023 Rad inhibited retron function by degrading noncoding RNA, the precursor of msDNA.
ugi APIS101 DNA repair CLAN077 Bacillus phage AR9 PMID: 6776115 Uracil-DNA-glycosylase inhibitor.
NTases APIS103 CBASS,Pycsar,CRISPR–Cas (type III) CLAN010 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) CLAN026 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) CLAN078 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) CLAN079 Escherichia phage Mu PMID:2934296 Methylcarbamoylase for DNA modification.
antiDnd_p0020 APIS113 Dnd CLAN044 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) CLAN080 Escherichia phage SECphi18 PMID:35725776 DNA polymerase
Ulx APIS119 restriction-modification (RM) CLAN081 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) CLAN045 Escherichia phage Ukendt PMID:38788717 Retron-Eco1 inhibitor
Lidtsur-6 APIS129 AVAST (Antiviral STAND) CLAN031 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 CLAN082 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 CLAN083 Vibrio cholerae PMID:32556263 CRISPR–Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats
MpaR APIS132 SOS response CLAN029 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 CLAN046 Vibrio cholerae PMID:32556263 CRISPR–Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats
hia5 APIS136 restriction-modification (RM) CLAN084 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) CLAN084 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) CLAN084 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) CLAN030 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) CLAN085 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 CLAN019 Pseudoalteromonas phage PH357 PMID:36952342 Functional screen identifies Atd1, a phage MazG-like suppressor of TIR-STING cell suicide
dmt APIS152 restriction-modification (RM) CLAN026 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 CLAN086 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) CLAN027 Escherichia phage JohannRWettstein Osterman et al., 2024 Phage enzyme ADPR-PP synthetase (Adps).
Lidtsur-17 APIS164 AVAST (Antiviral STAND) CLAN087 Escherichia phage Lidtsur PMID:35951700 Lidtsur-17 inhibits SeAvs3 nuclease activity in vitro.
Ddra APIS165 restriction-modification (RM) CLAN088 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) CLAN004 Vibrio cholerae PMID:32556263 vcrx089 and vcrx090 promote resistance against type I restriction-modification.
narp2_nmnat APIS170 NAD+ reconstitution pathway (NARP) CLAN020 Vibrio phage KVP40 Osterman et al., 2024 Nicotinamide mononucleotide adenylyltransferase (Nmnat), capable of generating NAD+ by conjugating AMP to NMN.
AriS APIS178 SOS response CLAN047 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) CLAN089 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 CLAN090 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 CLAN006 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) CLAN031 Escherichia phage forsur PMID:35951700 Forsur-7 inhibits SeAvs3 nuclease activity in vitro to a lesser degree.
AdfN APIS195 toxin-antitoxin (TA) CLAN091 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) CLAN011 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) CLAN111 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) CLAN112 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) CLAN005 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 CLAN114 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 CLAN048 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 CLAN117 Enterobacteriaceae Samuel and Burstein, 2023 SOS-inhibitor.
Stp Stp restriction-modification (RM) CLAN107 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) CLAN119 Vibrio cholerae PMID:32556263 vcrx089 and vcrx090 promote resistance against type I restriction-modification.
ADG.17 ADG.17 toxin-antitoxin (TA) CLAN055 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.
anti_TerI2 anti_TerI2 TerI CLAN110 Listeria monocytogenes 10403S Azulay et al., 2025 Anti-TerI2 counteract TerI during prophage induction to allow virion production.
anti_TerI1 APIS265 TerI CLAN053 Listeria monocytogenes 10403S Azulay et al., 2025 Anti-TerI1 counteract TerI during prophage induction to allow virion production.
T7K APIS276 Retron-Eco9,DarTG1 CLAN017 Escherichia phage T7 Bartolec et al., 2024 The T7 kinase weakens the activity of phage defense systems by phosphorylation, and is likely a broadly-acting phage counter-defense system.
acb4 APIS224 cyclic oligonucleotide-based antiphage signalling system (CBASS) CLAN093 Bacillus phage SPO1 PMID:40845805 Acb4 proteins bind nucleotide signals and inhibit a broad range of CBASS operons.
ZadI-1 APIS293 Zorya type I CLAN097 Pseudomonas phage vB_PaeM_SMS12 PMID:40639337 ZadI-1 inhibits Zorya type I defense, as shown by efficiency of plating, culture collapse,and phage propagation assays
Bdi1 APIS297 Zorya type I,RADAR,Hypnos,Druantia type I CLAN098 Pseudomonas phage PB1 PMID:40639337 Bdi1 and Bdi2 function as multipurpose anti-defense proteins capable of inhibiting four defense systems.
TadIII-1 TadIII-1 Thoeris type III CLAN108 Pseudomonas phage S50 PMID:40639337 TadIII-1 inhibits the anti-phage activity of Thoeris type III by a yet unknown mechanism
DadIII-1 DadIII-1 Druantia type III CLAN105 Pseudomonas phage PA_LZ7 PMID:40639337 DadIII-1 inhibits Druantia type III, most likely through a mechanism specifically targeting the activity of DruH, a protein unique to this Druantia type
Bdi2 Bdi2 Zorya type I,RADAR,Hypnos,Druantia type I CLAN104 Pseudomonas phage JG024 PMID:40639337 Bdi1 and Bdi2 function as multipurpose anti-defense proteins capable of inhibiting four defense systems.
SequestinJ APIS211 Thoeris CLAN001 PMID:41785351 Thoeris anti-defense sponge; sequesters 3′cADPR and blocks ThsA activation
SequestinM APIS245 Thoeris CLAN001 PMID:41785351 Sequestin-family anti-defense protein; inhibits type I Thoeris signaling, most likely by binding 3′cADPR.
SequestinD APIS283 Thoeris CLAN001 PMID:41785351 Thoeris anti-defense sponge; sequesters 3′cADPR and blocks ThsA activation
SequestinE APIS283 Thoeris CLAN001 PMID:41785351 Thoeris anti-defense sponge; sequesters 3′cADPR and blocks ThsA activation
Acb5A APIS287 Type I CBASS CLAN002 PMID:41785351 cleaves cyclic guanosine monophosphate–adenosine monosphosphate (3′3′-cGaMP) and related molecules
LockinE APIS288 Type II Thoeris CLAN003 PMID:41785351 Lockin-family type II Thoeris inhibitor; expected to neutralize the type II Thoeris signal His-ADPR.
LockinA APIS288 Type I Thoeris,Type II Thoeris CLAN003 B. subtilis phage SBSphiJ PMID:41785351 act as nucleotide “sponges,” binding 1′′–3′ glycocyclic adenosine diphosphate–ribose (3′caDPr) and histidine conjugated to aDPr (his- aDPr)
LockinD APIS288 Type I Thoeris,Type II Thoeris CLAN003 PMID:41785351 Lockin-family anti-defense sponge active against both type I and type II Thoeris; likely neutralizes 3′cADPR and His-ADPR immune signals.
SequestinK APIS315 Thoeris CLAN001 PMID:41785351 Sequestin-family Thoeris inhibitor; anti-defense protein that blocks the 3′cADPR → ThsA signaling pathway.
SequestinB APIS315 Thoeris CLAN001 PMID:41785351 Anti-Thoeris Sequestin-family sponge; neutralizes Thoeris signaling by trapping 3′cADPR and blocking downstream NAD-depletion defense.
SequestinL APIS315 Thoeris CLAN001 PMID:41785351 Viral anti-Thoeris sponge; binds/sequesters ADPR-derived Thoeris signal molecules and prevents growth-arrest/cell-death defense.
SequestinH APIS315 Thoeris CLAN001 PMID:41785351 Phage Sequestin homolog; functions as a Thoeris inhibitor by preventing immune-signal activation of the effector.
SequestinF APIS315 Thoeris CLAN001 PMID:41785351 Sequestin-family viral anti-defense protein; inhibits Thoeris by binding the TIR-produced ADPR-derived immune signal.
SequestinI APIS356 Thoeris CLAN001 PMID:41785351 Sequestin-family antidefense protein; neutralizes Thoeris signaling molecules and allows phage escape from Thoeris defense.
LockinB APIS359 Type I Thoeris CLAN003 PMID:41785351 Lockin-family type I Thoeris inhibitor; sponge protein that sequesters 3′cADPR, preventing Thoeris effector activation.
Acb5B APIS361 Type I CBASS CLAN002 PMID:41785351 cleaves cyclic guanosine monophosphate–adenosine monosphosphate (3′3′-cGaMP) and related molecules
SequestinC APIS372 Thoeris CLAN001 PMID:41785351 Small phage anti-defense protein from the Sequestin family; inhibits type I Thoeris by interfering with 3′cADPR-mediated immune activation.
SequestinG APIS373 Thoeris CLAN001 PMID:41785351 Anti-Thoeris sponge protein; blocks Thoeris immune signaling, likely through sequestration of 3′cADPR.
SequestinA APIS378 Thoeris CLAN001 PMID:41785351 Phage-encoded anti-Thoeris sponge protein; binds/sequesters the type I Thoeris immune signal 3′cADPR, preventing activation of the ThsA NADase effector.
LockinC LockinC Type I Thoeris CLAN003 PMID:41785351 Lockin-family sponge protein; inhibits type I Thoeris by trapping 3′cADPR.
dpda APIS204 restriction-modification (RM) CLAN028 Escherichia phage CAjan PMID:31784519 In Enterobacteria phage 9g, dpdA is associated with G+ synthesis. This modification is proposed to play an anti-restriction role because 7-deazaguanine derivatives can block the activity of a wide variety of restriction enzymes
fole APIS281 restriction-modification (RM) CLAN035 Enterobacteria phage 9g PMID:31784519 Enzyme to synthesize deazaguanines in G+ synthesis for anti-RM
qued APIS294 restriction-modification (RM) CLAN049 Enterobacteria phage 9g PMID:31784519 Enzyme to synthesize deazaguanines in G+ synthesis for anti-RM
quee APIS363 restriction-modification (RM) CLAN103 Enterobacteria phage 9g PMID:31784519 Enzyme to synthesize deazaguanines in G+ synthesis for anti-RM
jss1_004 APIS276 Dnd,QatABCD,SIR2+HerA,DUF4297+HerA,CRISPR‒Cas CLAN017 Salmonella phage JSS1 PMID:39506096 JSS1_004 employs N-terminal Ser/Thr/Tyr protein kinase activity to catalyse the multisite phosphorylation of host DndFGH. It also phosphorylates other bacterial immune systems to varying degrees, including CRISPR‒Cas, QatABCD, SIR2+HerA and DUF4297+HerA.
T5.014 APIS355 bNACHT CLAN102 Escherichia phage T5 PMID:37160116 The gene orf015 (T5.014) alter the activity of a wide variety of bNACHT genes and provide evidence for a complicated relationship between phage genes and bNACHT-based host defense systems, where orf008 activates and orf015 inhibits bNACHT proteins.
dap1 APIS292 Lon-mediated antiviral defense CLAN096 Pseudomonas phage PaoP5 PMID:38886583 Dap1 directly binds to phage HNH endonuclease, prohibiting host Lon-mediated HNH degradation and promoting phage genome packaging.
anhur anhur Septu CLAN109 Vibrio phage 1.196.O._10N.286.54.E12 Lopatina et al., 2024 Phage-encoded anti-Septu protein; inhibits the Septu/PtuAB ATPase–nuclease defense system and allows phage escape from Septu-mediated abortive infection.
surt APIS213 AbiU CLAN013 Vibrio phage 1.217.O._10N.261.45.A1 Lopatina et al., 2024 Phage anti-AbiU protein; counteracts AbiU abortive-infection defense and restores phage propagation in AbiU-containing hosts.
svarog APIS282 Septu CLAN095 Vibrio phage 1.066.O._10N.286.46.E8 Lopatina et al., 2024 Anti-Septu phage protein; functionally suppresses Septu defense, likely by interfering with the PtuAB effector module or its activation.
hades hades DRT type I CLAN054 Vibrio phage 1.066.O._10N.286.46.E8 Lopatina et al., 2024 Anti-DRT type I protein; phage-encoded inhibitor of DRT/retron-like defense, preventing type I DRT-mediated restriction or abortive infection.
kali kali DRT type III CLAN115 Vibrio phage 1.139.B._10N.261.48.C6 Lopatina et al., 2024 Anti-DRT type III protein; viral counter-defense factor that suppresses type III DRT activity during phage infection.
enki enki AbiH,Retron type II CLAN113 Vibrio phage 1.080.O._10N.286.48.A4 Lopatina et al., 2024 Broad anti-defense protein reported against AbiH and type II Retron systems; likely helps phage evade abortive-infection/retron-associated immune responses.
nergal nergal Type I CBASS CLAN116 Vibrio phage 1.209.O._10N.222.52.B2 Lopatina et al., 2024 Anti-CBASS type I protein; inhibits cyclic-oligonucleotide-based CBASS defense, probably by blocking signaling or effector activation.
tlaloc tlaloc AbiH CLAN118 Vibrio phage 1.056.O._10N.261.48.C11 Lopatina et al., 2024 Anti-AbiH protein; phage inhibitor of AbiH abortive-infection defense, allowing phage replication despite AbiH activity.
orf72 APIS244 BREX type I CLAN050 Escherichia phage Dru_SM1 Ojima et al., 2024 ORF72 has anti-Brex type I activity, was predicted to be a Plasmid replication region DNA-binding N-term
orf65 APIS307 hhe CLAN099 Escherichia phage Dru_SM1 Ojima et al., 2024 ORF65 shows anti-hhe activity, predicted as a transcriptional regulator protein (SplA).
orf55 APIS312 AVAST type III CLAN022 Escherichia phage Dru_SM1 Ojima et al., 2024 It has anti-AVAST type III activity, was predicted to be a ATP-dependent DNA ligase.
orf46 APIS325 BREX type I CLAN101 Escherichia phage Dru_SM1 Ojima et al., 2024 ORF46 exhibits anti-Brex type I activity, as a trimethylamine methyltransferase corrinoid protein.
orf58 APIS345 Sir2-HerA,DUF4297-HerA CLAN032 Escherichia phage Dru_SM1 Ojima et al., 2024 ORF58 has anti-SIR2+HerA and DUF4297+HerA activity as well as Reron Ec86 sensor activity, was predicted to be a “Mu-like prophage host-nuclease inhibitor protein Gam
orf83 APIS354 AVAST type III CLAN012 Escherichia phage Dru_SM1 Ojima et al., 2024 ORF83 exhibits anti-AVAST type III activity, was predicted to be a “nucleotide-binding protein DprA/Smf involved in DNA uptake”.
Druad1 Druad1 Druantia type I CLAN106 Escherichia phage Dru_SM1 Ojima et al., 2024 ORF71 exhibits anti-Druantia type I activity, was predicted to belong to a family of unknown function (DUF6614).
adfB APIS207 toxin-antitoxin (TA) CLAN092 Vibrio phage ICP1 PMID:39287445 AdfB functions as an antitoxin, abrogating DarT toxicity through direct interactions.
oad1 APIS269 Class 1 OLD nucleases CLAN094 Vibrio phage ICP1 PMID:39829814 OLD anti-defense 1 (Oad1) is a direct inhibitor of Vibrio cholerae-encoded Class 1 OLD family nuclease.
orf35 APIS308 Tmn CLAN100 Escherichia phage SM_S22 PMID:39987292 Deletion of ORF35 from the ΦSMS22 genome resulted in reduced infectivity against E. coli expressing Tmn, suggesting that ORF35 functions as an anti-Tmn
Tad6 APIS240 type I Thoeris CLAN016 PMID:39855193 Tad3, Tad4, and Tad6 each have a conserved loop that blocks the active site pocket and interacts with the catalytic E85 residue of the type I ThsB
Tad7 APIS242 type II Thoeris CLAN033 PMID:39855193 The conserved loop of Tad7 binds the catalytic E99 residue of type II ThsB via a hydrogen bond.
Tad4 APIS258 type I Thoeris CLAN015 PMID:39855193 Tad3, Tad4, and Tad6 each have a conserved loop that blocks the active site pocket and interacts with the catalytic E85 residue of the type I ThsB.
Tad8 APIS270 type II Thoeris CLAN034 PMID:39855193 The conserved loops in Tad8 occupy the pocket within ThsA responsible for His-ADPR binding.
Tad3 APIS351 type I Thoeris CLAN014 PMID:39855193 Tad3, Tad4, and Tad6 each have a conserved loop that blocks the active site pocket and interacts with the catalytic E85 residue of the type I ThsB.
acb3 APIS369 type III CBASS CLAN007 PMID:39855193 Acb3 encodes a conserved loop that is predicted to block the active site of CD-NTases and interact with the nucleotidyltransferase catalytic residues via hydrogen and ionic bonds. 
Tad5 Tad5 type I Thoeris CLAN052 PMID:39855193 Tad5 can interact with E85 and other active site residues in ThsB but does not completely block the active site pocket.
T5Dmp APIS279 Kongming CLAN021 Escherichia phage T5 PMID:39977546 A deoxyribonucleoside 5′-monophosphatase functions as an anti-Kongming factor.
bas26_0202 APIS279 Kongming CLAN021 Escherichia phage GreteKellenberger PMID:39977546 The protein robustly suppressed cell death triggered by Kongming and their respective DNKs, indicating anti-Kongming function.
VPG01_164 APIS286 Kongming CLAN021 Vibrio phage VPG01 PMID:39977546 The protein robustly suppressed cell death triggered by Kongming and their respective DNKs, indicating anti-Kongming function.
dap2 dap2 Lon-mediated antiviral defence CLAN051 Pseudomonas phage PaoP5 Zhao et al., 2025 Dap2 directly binds to the Lon protease to prevent the degradation of the phage-encoded HNH endonuclease.