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Table 1
Protein components of CASS
	Family	Subfamily^A	Phyletic distribution^B	Comments

1	COG1518	COG1518 (cas1)	All	Putative novel nuclease/integrase; Mostly α-helical protein
2	COG1343	COG1343 (cas2), COG3512, ygbF-like; MTH324-like; y1723_N-like;	All	Small protein related to VapD, fused to helicase (COG1203) in y1723-like proteins
3	COG1203	COG1203 (cas3)	All	DNA helicase; Most proteins have fusion to HD nuclease
4	RecB-like nuclease	COG1468 (cas4), COG4343	All	RecB-like nuclease; Contains three-cysteine C-terminal cluster
5	RAMP	COG1688, COG1769, COG1583, COG1567, COG1336, COG1367, COG1604, COG1337, COG1332, COG5551, BH0337-like, MJ0978-like, YgcH-like, y1726-like, y1727-like	All	Belong to "RAMP" superfamily, possibly RNA-binding protein, structurally related to a duplicated ferredoxin fold (PDB: 1WJ9)
6	COG1857	COG1857, COG3649, YgcJ-like, y1725-like	All	α/β protein; probable enzymatic activity, possibly, a nuclease
7	HD-like nuclease	COG1203 (N-terminus), COG2254	All	HD-like nuclease
8	BH0338	BH0338-like MTH1090-like	All, mostly archaea and FIRM	Large Zn-finger-containing proteins, possibly, nucleases (nuclease activity has been reported for MTH1090 [75].
9	ygcL	ygcL	Bacteria, mostly PROTEO	Large Zn-finger containing proteins;
10	COG1353	COG1353, MTH326-like, alr1562, slr7011	All, mostly Archaea	Putative novel polymerase; Multidomain protein with permuted HD nuclease domain, palm domain, polymerase-thumb-like domain and Zn-ribbon; MTH326-like has inactivated polymerase catalytic domain; alr1562 and slr7011 – predicted only on the basis of size, presence of HD domain, and location with RAMPs in one operon
11	COG1517/HTH	COG2462	Archaea	Former COG2462; Fusion of COG1517-like domain to HTH-type transcriptional regulator; Possible regulator of the system expression in archaea
12	COG1421	COG1421	All, mostly Archaea	~150 aa protein; Has a few motifs similar to ygcK-like; mostly α-helical protein
13	ygcK	ygcK-like	Bacteria, mostly PROTEO	~180 aa protein; has a few motifs similar to COG1421; mostly α-helical protein
14	COG3337	COG3337	All, mostly Archaea	~110 aa; mostly α-helical protein
15	COG1517	COG1517 COG4006	All, mostly Archaea	Some are fused to HTH domain (see COG1517/HTH), some proteins have the domain duplication; structure is available (1XMX); domain appears to have a Rossmann-like fold.
16	COG3513	COG3513	Bacteria, mostly PROTEO	Huge protein; contains McrA/HNH-nuclease related domain and RuvC-like nuclease domain
17	PH0918	PH0918-like	All, mostly Archaea	Specific for Pyrococcus and Thermococcus. The pair ST0031/SSO1401 and AF1873, most likely, belong to the same family because have similar length and located in the identical place in an operon but due to low conservation are not alignable
18	AF1870	AF1870-like	Archaea	Former COG3574; ~150 aa protein.
19	AF0070	AF0070-like	Archaea	~420 aa protein, no prediction
20	y1724	y1724-like	Bacteria, mostly PROTEO	~450 aa protein, no prediction
21	SPy1049	Spy1049-like	Bacteria, mostly FIRM	~220 aa protein, no prediction
22	TTE2665	TTE2665-like	Bacteria, mostly CHLOR	~130 aa protein, no prediction
23	LA3191	LA3191-like	Few bacteria	~650 aa, no prediction

^A– Subfamilies are named by the corresponding COG number or by a protein ID ^B– All indicates that the family is widespread in all major prokaryotic lineages; PROTEO – proteobacteria; FIRM – firmicutes; CHLOR – Chlorobia
Makarova et al. Biology Direct 2006 1:7 doi:10.1186/1745-6150-1-7

Table 1