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Browse anti-prokaryotic immune system protein families

The list of 201 APIS protein families built from close homologs of 84 seed proteins in four virome/phage DBs

APIS families APIS genes Immune system CLAN ID Phages/MGEs References Description
APIS001 Apyc1 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.
APIS002 vs.4 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.
APIS003 ArdA 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.
APIS004 Acb2 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.
APIS005 Gad1 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.
APIS006 abc1 RecBCD CLAN005 Salmonella phage S149 Silas et al., 2023 Trigger programmed cell death (PCD) by P4 prophage.
APIS007 KlcA 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.
APIS008 Gad2 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.
APIS009 Ral 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.
APIS010 Ocr 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.
APIS011 gp4.5 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.
APIS012 tifA 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.
APIS013 Dmd 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.
APIS014 PinA 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.
APIS015 IpII 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.
APIS016 Acb1 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.
APIS017 Alt 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.
APIS018 Arn 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.
APIS019 gnarl2 O-antigen-based barrier CLAN018 Escherichia phage Mu Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
APIS020 Abc2 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.
APIS021 SieA restriction-modification (RM) CLAN020 Salmonella phage P22 Silas et al., 2023 Superinfection exclusion.
APIS022 adfA toxin-antitoxin (TA) CLAN021 RB69 of E. coli PMID:35725776 Gene adfA(gp61.2) is encoded as a DarT (TA system) inhibitor.
APIS023 gp5.9 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.
APIS024 Tad1 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.
APIS025 Had1 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.
APIS026 orf126 broad-spectrum counter-defense CLAN025 Salmonella phage SPFM20 Silas et al., 2023 Broad-spectrum counter-defense.
APIS027 DSAD1 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.
APIS029 Tad2 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.
APIS030 DarB 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.
APIS031 DarA 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.
APIS032 Cor superinfection exclusion CLAN029 Enterobacteria phage phi80 PMID:15518820 Superinfection exclusion, inactivates FhuA receptor.
APIS033 Lar 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.
APIS034 gnarl1 O-antigen-based barrier CLAN031 Klebsiella phage vB_KpnM_KpV79 Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
APIS035 orf148 broad-spectrum counter-defense CLAN032 Escherichia phage OSYSP Silas et al., 2023 Broad-spectrum counter-defense.
APIS036 gnarl3 O-antigen-based barrier CLAN033 Escherichia phage Mangalitsa Silas et al., 2023 Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
APIS037 CLAN006
APIS038 CLAN006
APIS039 CLAN006
APIS040 CLAN030
APIS041 CLAN001
APIS042 CLAN020
APIS043 CLAN023 Pasteurella phage Pm86
APIS044 CLAN001 Bacillus phage W.Ph.
APIS045 CLAN023
APIS046 CLAN004
APIS047 CLAN032
APIS048 CLAN002 Ralstonia phage YO108_2
APIS049 CLAN005
APIS050 CLAN032
APIS051 CLAN003
APIS052 CLAN023
APIS053 CLAN004
APIS054 CLAN001
APIS055 CLAN006 Pseudomonas phage Churro
APIS056 CLAN007
APIS057 CLAN004
APIS058 CLAN001
APIS059 CLAN007 Pseudoalteromonas phage HM1
APIS060 CLAN001
APIS061 CLAN023
APIS062 CLAN001
APIS063 CLAN003
APIS064 CLAN001
APIS065 CLAN004 Shewanella sp. phage 1/4
APIS066 CLAN001
APIS067 CLAN003
APIS068 CLAN004
APIS069 CLAN006
APIS070 CLAN023
APIS071 CLAN004
APIS072 CLAN003
APIS073 CLAN001
APIS074 CLAN032
APIS075 CLAN032 Pectobacterium phage A38
APIS076 CLAN001
APIS077 CLAN009 Proteus phage PM 116
APIS078 CLAN010 Morganella phage vB_MmoP_MP2
APIS079 CLAN023 Pseudomonas phage Skulduggery
APIS080 CLAN010 Klebsiella phage VLCpiA3d
APIS081 CLAN028
APIS082 CLAN032
APIS083 CLAN004 Clostridioides phage ES-S-0107-01
APIS084 CLAN010 Pectobacterium phage phiPccP-1
APIS085 CLAN009 Escherichia phage T7
APIS086 CLAN011 Escherichia phage vB_EcoM_CE1
APIS087 CLAN009 Shigella phage ESh23
APIS088 CLAN004
APIS089 CLAN007
APIS090 IpI 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.
APIS091 HOS17_gp01 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.
APIS092 Gam RecBCD CLAN036 Lambda of E. coli PMID:24086157 The protein Gam inhibits the host RecBCD exonuclease activity thus allowing efficient rolling-circle replication.
APIS093 CLAN035 Pantoea phage vB_PagP-SK1
APIS094 Rad Retron CLAN037 Escherichia phage SP15 Azam et al., 2023 Rad inhibited retron function by degrading noncoding RNA, the precursor of msDNA.
APIS095 CLAN038
APIS096 CLAN039
APIS097 CLAN003
APIS098 CLAN003
APIS099 CLAN038
APIS100 CLAN006
APIS101 ugi DNA repair CLAN040 Bacillus phage AR9 PMID: 6776115 Uracil-DNA-glycosylase inhibitor.
APIS102 CLAN041
APIS103 NTases 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). 
APIS104 narp2_nampt NAD+ reconstitution pathway (NARP) CLAN043 Vibrio phage KVP40 Osterman et al., 2024 Nicotinamide phosphoribosyltransferase activity (Nampt), capable of producing NMN from PRPP and nicotinamide.
APIS105 CLAN039
APIS106 CLAN044
APIS107 dam 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.
APIS108 ardc 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.
APIS109 CLAN038
APIS110 CLAN039
APIS111 mom restriction-modification (RM) CLAN047 Escherichia phage Mu PMID:2934296 Methylcarbamoylase for DNA modification.
APIS112 CLAN038
APIS113 antiDnd_p0020 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.
APIS114 CLAN048
APIS115 CLAN049
APIS116 CLAN037
APIS117 mga47 toxin-antitoxin (TA) CLAN050 Escherichia phage SECphi18 PMID:35725776 DNA polymerase
APIS118 CLAN044
APIS119 Ulx 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.
APIS120 CLAN038
APIS121 CLAN042
APIS122 CLAN042
APIS123 CLAN038
APIS124 CLAN028
APIS125 U56 toxin-antitoxin (TA) CLAN052 Escherichia phage Ukendt PMID:38788717 Retron-Eco1 inhibitor
APIS126 CLAN044
APIS127 CLAN039
APIS128 CLAN003
APIS129 Lidtsur-6 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.
APIS130 RacC 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.
APIS131 vcrx091 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
APIS132 MpaR 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.
APIS133 vcrx092 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
APIS134 CLAN039
APIS135 CLAN028
APIS136 hia5 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.
APIS136 hin1523 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.
APIS136 nma1821 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.
APIS137 CLAN042
APIS138 CLAN057
APIS139 CLAN039
APIS140 CLAN053
APIS141 CLAN049
APIS142 CLAN037
APIS143 Hdf 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.
APIS144 CLAN042
APIS145 CLAN057
APIS146 CLAN003
APIS147 CLAN003
APIS148 OrbA 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.
APIS149 CLAN056
APIS150 Atd1 TIR-STING CLAN044 Pseudoalteromonas phage PH357 PMID:36952342 Functional screen identifies Atd1, a phage MazG-like suppressor of TIR-STING cell suicide
APIS151 CLAN049
APIS152 dmt 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.
APIS153 antiDnd_p0021 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.
APIS154 CLAN038
APIS155 CLAN042
APIS156 CLAN060
APIS157 CLAN039
APIS158 CLAN049
APIS159 CLAN003
APIS160 narp1_adps NAD+ reconstitution pathway (NARP) CLAN057 Escherichia phage JohannRWettstein Osterman et al., 2024 Phage enzyme ADPR-PP synthetase (Adps).
APIS161 CLAN045
APIS162 CLAN044
APIS163 CLAN042
APIS164 Lidtsur-17 AVAST (Antiviral STAND) CLAN061 Escherichia phage Lidtsur PMID:35951700 Lidtsur-17 inhibits SeAvs3 nuclease activity in vitro.
APIS165 Ddra 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.
APIS166 vcrx089 restriction-modification (RM) CLAN039 Vibrio cholerae PMID:32556263 vcrx089 and vcrx090 promote resistance against type I restriction-modification.
APIS167 CLAN052
APIS168 CLAN042
APIS169 CLAN038
APIS170 narp2_nmnat 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.
APIS171 CLAN039
APIS172 CLAN038
APIS173 CLAN038
APIS174 CLAN057
APIS175 CLAN039
APIS176 CLAN003
APIS177 CLAN038
APIS178 AriS 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.
APIS179 Ddrb 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.
APIS180 psib SOS response CLAN064 Escherichia coli PMID:19818715 PsiB protein works as an SOS inhibitor that binds to RecA to inhibit its activities.
APIS181 CLAN041
APIS182 CLAN039
APIS183 CLAN039
APIS184 CLAN039
APIS185 vcrx093 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
APIS186 CLAN039
APIS187 CLAN003
APIS188 CLAN038
APIS189 CLAN042
APIS190 CLAN039
APIS191 CLAN037
APIS192 CLAN045
APIS193 Forsur-7 AVAST (Antiviral STAND) CLAN053 Escherichia phage forsur PMID:35951700 Forsur-7 inhibits SeAvs3 nuclease activity in vitro to a lesser degree.
APIS194 CLAN003
APIS195 AdfN 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.
APIS196 CLAN038
APIS197 narp1_namat NAD+ reconstitution pathway (NARP) CLAN043 Escherichia phage JohannRWettstein Osterman et al., 2024 Phage enzyme Nicotinamide ADPR-transferase (Namat)
APIS198 CLAN039
APIS199 CLAN038
APIS200 CLAN066