Browse anti-prokaryotic immune system protein families

The list of 92 APIS protein families built from close homologs of 41 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)	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.
APIS002	vs.4	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.
APIS003	ArdA	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.
APIS004	Acb2	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.
APIS005	Gad1	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.
APIS006	abc1	RecBCD	CLAN014	Salmonella phage S149	Silas et al., 2023	Trigger programmed cell death (PCD) by P4 prophage.
APIS007	KlcA	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.
APIS008	Gad2	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.
APIS009	Ral	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.
APIS010	Ocr	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.
APIS011	gp4.5	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.
APIS012	tifA	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.
APIS013	Dmd	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.
APIS014	PinA	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.
APIS015	IpII	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.
APIS016	Acb1	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.
APIS017	Alt	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.
APIS018	Arn	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.
APIS019	gnarl2	O-antigen-based barrier	CLAN035	Escherichia phage Mu	Silas et al., 2023	Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
APIS020	Abc2	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.
APIS021	SieA	restriction-modification (RM)	CLAN005	Salmonella phage P22	Silas et al., 2023	Superinfection exclusion.
APIS022	adfA	toxin-antitoxin (TA)	CLAN025	RB69 of E. coli	PMID:35725776	Gene adfA(gp61.2) is encoded as a DarT (TA system) inhibitor.
APIS023	gp5.9	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.
APIS024	Tad1	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.
APIS025	Had1	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.
APIS026	orf126	broad-spectrum counter-defense	CLAN029	Salmonella phage SPFM20	Silas et al., 2023	Broad-spectrum counter-defense.
APIS027	DSAD1	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.
APIS029	Tad2	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.
APIS030	DarB	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.
APIS031	DarA	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.
APIS032	Cor	superinfection exclusion	CLAN032	Enterobacteria phage phi80	PMID:15518820	Superinfection exclusion, inactivates FhuA receptor.
APIS033	Lar	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.
APIS034	gnarl1	O-antigen-based barrier	CLAN036	Klebsiella phage vB_KpnM_KpV79	Silas et al., 2023	Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
APIS035	orf148	broad-spectrum counter-defense	CLAN028	Escherichia phage OSYSP	Silas et al., 2023	Broad-spectrum counter-defense.
APIS036	gnarl3	O-antigen-based barrier	CLAN034	Escherichia phage Mangalitsa	Silas et al., 2023	Putative O-antigen modifiers, interfere with O-antigen biosynthesis.
APIS037			CLAN003
APIS038			CLAN003
APIS039			CLAN003
APIS040			CLAN007
APIS041			CLAN030
APIS042			CLAN005
APIS043			CLAN031	Pasteurella phage Pm86
APIS044			CLAN030	Bacillus phage W.Ph.
APIS045			CLAN031
APIS046			CLAN001
APIS047			CLAN028
APIS048			CLAN018	Ralstonia phage YO108_2
APIS049			CLAN014
APIS050			CLAN028
APIS051			CLAN004
APIS052			CLAN031
APIS053			CLAN001
APIS054			CLAN030
APIS055			CLAN003	Pseudomonas phage Churro
APIS056			CLAN002
APIS057			CLAN001
APIS058			CLAN030
APIS059			CLAN002	Pseudoalteromonas phage HM1
APIS060			CLAN030
APIS061			CLAN031
APIS062			CLAN030
APIS063			CLAN004
APIS064			CLAN030
APIS065			CLAN001	Shewanella sp. phage 1/4
APIS066			CLAN030
APIS067			CLAN004
APIS068			CLAN001
APIS069			CLAN003
APIS070			CLAN031
APIS071			CLAN001
APIS072			CLAN004
APIS073			CLAN030
APIS074			CLAN028
APIS075			CLAN028	Pectobacterium phage A38
APIS076			CLAN030
APIS077			CLAN020	Proteus phage PM 116
APIS078			CLAN023	Morganella phage vB_MmoP_MP2
APIS079			CLAN031	Pseudomonas phage Skulduggery
APIS080			CLAN023	Klebsiella phage VLCpiA3d
APIS081			CLAN006
APIS082			CLAN028
APIS083			CLAN001	Clostridioides phage ES-S-0107-01
APIS084			CLAN023	Pectobacterium phage phiPccP-1
APIS085			CLAN020	Escherichia phage T7
APIS086			CLAN022	Escherichia phage vB_EcoM_CE1
APIS087			CLAN020	Shigella phage ESh23
APIS088			CLAN001
APIS089			CLAN002
APIS090	IpI	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.
APIS091	HOS17_gp01	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.
APIS092	Gam	RecBCD	CLAN021	Lambda of E. coli	PMID:24086157	The protein Gam inhibits the host RecBCD exonuclease activity thus allowing efficient rolling-circle replication.
APIS093			CLAN015	Pantoea phage vB_PagP-SK1