Table 1.
Classification of CARF and SAVED domains
| Group | Number of proteins* | Frequent fusions with enzymatic domains | CRISPR-CAS link | Taxonomic spread | Closest PFAM | CDD HHpred∧ | Comments |
|---|---|---|---|---|---|---|---|
| CARF1 | 329 | HEPN | CAS-III-A mostly | Mostly, bacteria | PF09659 | cd09699 | Known as Csm6 family |
| CARF2 | 239 | HEPN, mCpol | CAS-III | Archaea and bacteria | PF09455 | cd09732 | Known as Csx1 family; some lost HEPN |
| CARF3 | 436 | No | CAS-I mostly | Mostly, archaea and some bacteria | PF09002 | cd09655 | Known as Csa3 (or CasR) family |
| CARF4 | 400 | PD-D/ExK, csx16, AAA ATPase | partially | Mostly, bacteria | PF09002 | cd09723 | Some fused to other CARF4 domains; known as Can1 |
| CARF5 | 128 | ADA | CAS-III | Archaea and bacteria | PF09623 | cd09686 | |
| CARF6 | 167 | STK_AAA | No | Mostly bacteria, some Thaumarchaeota | PF06956 | cd09655 | Two fused CARF domains, often in defense islands, sometimes encoded within T7 transposon |
| CARF7 | 154 | RelE, CYTH, HD | CAS-III | Bacteria and some archaea, mostly, Crenarchaeota | PF09651 | cd09694 | Established ring nuclease Crn1 |
| CARF8 | 50 | csx16 | CAS-III | Archaea and bacteria | cd09747 | Membrane associated (2–4 segments) | |
| CARF9 | 183 | HEPN | CAS-III | Archaeal and bacterial thermophiles | PF09455 | cd09728 | Known as Csx1 family |
| SAVED1 | 176 | HNH or PD-D/ExK | No | Mostly, bacteria | PF18145 | Linked to 2′-5′ oligoA synthetase | |
| SAVED2 | 119 | peptidase M48, CHAT, nucleosidase | No | Bacteria only | PF18145 | 2TM or 3TM, linked to 2′-5′ oligoA synthetase | |
| SAVED3 | 122 | PD-D/ExK | Partially | Bacteria only | PF18179 | Some have 2TM (typically not fused with other domains); linked to 2′-5′ oligoA synthetase and often to ubiquitin system components: ubiquitin activating E1 and E2 family enzymes and JAB protease | |
| SAVED4 | 33 | LON | CAS-III | Mostly, bacteria | PF18145 | Mostly membrane, some don’t have LON domain | |
| SAVED5 | 27 | TIR, JAB | Partially | Mostly, bacteria | PF18145 | Some linked to 2′-5′ oligoA synthetase | |
| SAVED6 | 14 | No | Partially (CAS-III-D) | Actinobacteria | PF18145 | ||
| SAVED7 | 35 | No | No | Bacteria only | PF18145 | Mostly membrane | |
| RtcR | 1925 | ||||||
| RtcR | AAA | No | Proteobacteria only | PF06956 | cd09723 | Linked to RNA cyclase RtcA, RNA ligase RtcB, TROVE domain, stomatin-like proteins | |
| PspF1 | AAA | No | Bacteria only | PF06956 | cd09723 | Defense island context, often encoded within Tn7 transposon | |
| PspF2 | AAA | No | Bacteria only | PF06956 | cd09723 | Defense island context | |
| CARF_m1 | 54 | PIN | Partially | Archaea only (Crenarchaeota) | Only those with PIN domain are encoded in the loci with type III systems | ||
| CARF_m2 | 2 | LON | No | Mostly Planctomycetes | cd09747 | ||
| CARF_m3 | 47 | PIN | Partially type III | Archaea (Thermoprotei only) | cd09723 | ||
| CARF_m4 | 5 | No | CAS-III | Archaea (Thermoprotei only) | cd09694 | ||
| CARF_m5 | 5# | No | No | Asgard archaea | PF09002 | cd09723 | |
| CARF_m6 | 4 | unk_domain | No | Haloferax only | cd09655 | ||
| CARF_m7 | 4 | Nitrilase | CAS-III | Archaea (Methanosarcinales only) | cd09747 | ||
| CARF_m9 | 9 | No | No | Mostly, cyanobacteria | cd09723 | Membrane associated, several either fused or encoded next to linked to mCpol | |
| CARF_m10 | 3 | HEPN | CAS-III-D | Bacteria | cd09699 | ||
| CARF_m11 | 15 | HEPN, CorA | CAS-III-D | Actinobacteria only | cd09742 | ||
| CARF_m12 | 7 | PIN | No | Archaea (Desulfurococcales only) | cd09723 | Often co-occurred with type I-A CRISPR–Cas system | |
| CARF_m13 | 37 | No | Partially type III | Archaea (Thermoprotei only) | cd09723 | Established ring nuclease Crn1 |
Note: * – in prok1903 (redundant); # – five distinct CARF proteins from Asgard archaea, not represented among complete genomes; ∧ – best hit in HHpred with probability >90% (however, many homologous CDD profiles have very close probability values, so relationships are approximate).