Table S1 (Shah et al. 2018, preprint PDF)

CRISPR-Cas Type III accessory protein families

List of putative accessory gene clusters conserved near Type III genetic modules which passed the Type III association score cut-off (>24). All annotated accessory protein sequences are available in Shah2018.TypeIIIaccessory.faa. For each putative accessory protein family, the cluster id, the size (i.e. number of members per cluster), and the calculated Type III association score are listed. An example (gene-) locus id is also provided for reference. Names are provided for accessory protein families identified in earlier studies (Haft et al. 2005; Vestergaard et al. 2014; Makarova et al. 2015). Thirty nine of 76 putative accessory protein families are newly identified. Links to sequence alignments, gene and genome maps are provided as well as profile-profile alignment results against Pfam and PDB. A rudimentary functional prediction is given in the last two columns.

cluster	name	score	size	length	example	links	comment	description
1	Csx1/Csm6	73.88	116	446	J114_15030	ALN Gene Pfam PDB	CARF+HEPN	N-ter CARF, C-ter HEPN toxin
2	Csx1	69.25	94	464	Thet_1098	ALN Gene Pfam PDB	CARF+HEPN	N-ter CARF, C-ter HEPN toxin
3	Csm6	62.33	69	347	NIES39_J03350	ALN Gene Pfam PDB	CARF+RelE	N-ter CARF, C-ter RelE toxin
5	Cas11/Csx19	59.36	64	179	Athe_0139	ALN Gene Pfam PDB	core gene (SS)
6	Csx1	58.51	61	461	aq_378	ALN Gene Pfam PDB	CARF+HEPN	N-ter CARF, C-ter HEPN toxin
7	WYL/Csx1	42.59	51	335	THEYE_A0059	ALN Gene Pfam PDB	CARF+WYL	N-ter CARF, C-ter WYL
9	Csx1	37.91	49	399	PTH_1930	ALN Gene Pfam PDB	CARF+Nuclease	N-ter CARF, C-ter putative endonuclease
11	Csx15/20/peptidase	35.59	41	129	Vpar_1818	ALN Gene Pfam PDB	peptidase	peptidase associated with CRISPR3 in Synecocystis. Suggests an unknown step, may be a proteolytic maturation of some Cas protein
17	Cas_RecF	24.7	31	331	Tneu_0569	ALN Gene Pfam PDB	SMC ATPase	ABC AAA ATPase cassette found in SMC type DNA repair proteins. Called CasRecF in Vestergaard et al. 2014
23	Csx1	4.61	20	378	LS215_0610	ALN Gene Pfam PDB	found elsewhere	CARF protein also found elsewhere on the genome far from Type III modules
25	Csx3	55.83	18	100	THEYE_A0067	ALN Gene Pfam PDB	Csx3 (CARF)
27	Csx18	50.07	17	94	sll7069	ALN Gene Pfam PDB	adaptation associated	found in cyanobacterial Type III systems that have an adaptation module
28	Csx21	66.76	17	229	Cyan7425_0157	ALN Gene Pfam PDB	Type III-D associated	possible C-terminal RNA binding domain. Associated exclusively with Type III-D systems
29	CorA	45.91	14	572	CLB_2115	ALN Gene Pfam PDB	CorA-like	C-ter. CorA-like Mg2+ transporter domain. N-ter. domain unknown. Associated with Type III-B modules in bacteria and archaea.
33	Csa3	10.47	13	215	Pcal_0266	ALN Gene Pfam PDB	Type I-A associated	CARF-HTH or Csa3 normally associated with Type I-A systems as a transcriptional repressor or activator
35	Csx3	61.07	12	310	CYB_0599	ALN Gene Pfam PDB	Csx3-AAA
36	WYL	50.71	11	451	Mic7113_2620	ALN Gene Pfam PDB	HTH-WYL	N-ter. DNA binding domain and C-ter WYL domain that may be involved in regulation (mainly cyanobacteria)
37	Csx26	56.62	11	125	M1627_1089	ALN Gene Pfam PDB	HNH nuclease	restriction endonuclease/HNH endonuclease
38	C3a38	54.35	10	277	CLOAM0849	ALN Gene Pfam PDB	unknown	Unknown structure/function
42	Cas11/Csx19	74.4	9	140	FSU_2045	ALN Gene Pfam PDB	core gene (SS)	CasT3 - specific for bacterial type III-A/III-B systems
43	C3a43	58.83	9	492	Ferpe_1557	ALN Gene Pfam PDB	Lon protease	likely ATP-dependent protease domain at N-ter. (Lon family). Large unknown C-terminal domain.
45	PD-DExK	28.54	9	288	Dd586_3238	ALN Gene Pfam PDB	possible nuclease	Possible nuclease-related domain at C-terminal end
47	protease	27.09	9	103	YN1551_2381	ALN Gene Pfam PDB	peptidase	peptidase like cluster 11. The finding of peptidases as part of the accessory proteome, both in achaea and in some baceria points at an unknown step. Possible proteolytic maturation or activation of some Cas protein.
50	Csx1	61.07	8	277	Cpha266_2053	ALN Gene Pfam PDB	TM+CARF	N-ter trans membrane, C-ter CARF
55	C3a55	44.44	7	283	Riv7116_3423	ALN Gene Pfam PDB	ABC permease	likely oligonucleotide ABC transporter permease
57	HerA	20.46	7	583	Vdis_1158	ALN Gene Pfam PDB	Type III coevolved	HerA helicase normally involved in DNA repair, but this version of it has coevolved with crenarchaeal Type III modules
58	NurA	33.01	7	348	Cmaq_1511	ALN Gene Pfam PDB	Type III coevolved	NurA-like nuclease: ssDNA endonuclease and 5'-3' exonuclease on ss or dsDNA
59	C3a59	55.84	7	178	Nos7107_2826	ALN Gene Pfam PDB	Trans-membrane (TM)	transmembrane, unknown structure/function
64	C3a64	43.07	7	78	M1627_1085	ALN Gene Pfam PDB	Unknown	unknown structure/function
67	C3a67	40.03	6	388	Cagg_1075	ALN Gene Pfam PDB	AAA-Csx3	Csx3 at C-terminus; looks like nucleotidyl phosphokinase at N-terminus
69	C3a69	29.69	6	125	B005_5545	ALN Gene Pfam PDB	unknown	unknown structure-function
76	C3a76	39	6	96	Ssol_2352	ALN Gene Pfam PDB	unknown	unknown structure-function
77	Csx16	29.73	6	99	NE0116	ALN Gene Pfam PDB	a.k.a. cas_VVA1548
80	C3a80	27.48	6	1184	Metvu_1289	ALN Gene Pfam PDB	AAA+ ATPase	AAA+ ATPase, DUF499 family, unknown function
81	Csx1	-9.48	6	179	M1425_0870	ALN Gene Pfam PDB	Type I associated	small CARF protein often also associated with Type I systems
83	cas_RFas	88.69	6	157	VMUT_1493	ALN Gene Pfam PDB	cluster 17 associated	unknown structure-function, always associated with Cas-RecF, cluster 17
84	cas_RFas	66.57	6	128	VMUT_1494	ALN Gene Pfam PDB	cluster 17 associated	possible RNA recognition motif (RRM) at N-ter. Always associated with Cas-RecF, cluster 17
87	Cmr7	74.65	6	185	LS215_0814	ALN Gene Pfam PDB	Cmr7	Cmr7 (Sulfolobus)
93	C3a93	30.57	5	155	Thit_1351	ALN Gene Pfam PDB	poss. AAA ATPase	likely AAA+ ATPase
96	Mvol_0529-fam	42.25	5	125	CLB_2116	ALN Gene Pfam PDB	DNA binding C-ter.	possible DNA binding C-ter. domain
104	Csx1	39.74	5	466	PYCH_07970	ALN Gene Pfam PDB	CARF+PIN	N-ter CARF, C-ter PIN toxin
107	Csx1	84.37	5	680	TTHB155	ALN Gene Pfam PDB	CARF	large CARF protein with interspersed stretches of sequence that have no significant domain matches
108	cas_RFas	78.8	5	180	Tneu_0568	ALN Gene Pfam PDB	cluster 17 associated	unknown structure-function, always associated with Cas-RecF, cluster 17
116	C3a116	57.92	4	257	AZL_010430	ALN Gene Pfam PDB	cluster 29 associated	unknown structure-function, always associated with CorA, cluster 29
121	Csx23	62.04	4	168	CFF8240_1673	ALN Gene Pfam PDB	unknown	unknown structure-function
123	C3a123	37.09	4	211	Cagg_1060	ALN Gene Pfam PDB	unknown	unknown structure/function
124	C3a124	44.42	4	433	Cyan10605_3519	ALN Gene Pfam PDB	unknown	SYNPCC7002_F0039 has an SMC_N domain pointing at a function in DNA metabolism and recombination such as recN, recF. The gbk entry for SYNPCC7002_F003 states that Slr7100 is a homolog, which seems unlikely. However, the latter is CRISPR3-associated.
139	C3a139	28.91	4	1158	Metvu_1226	ALN Gene Pfam PDB	HKD+Snf2	N-ter. HKD family nuclease fused to C-ter. Snf2-like helicase domain which has no helicase activity
146	C3a146	68.43	4	177	SSO1421	ALN Gene Pfam PDB	DNA binding HTH	Likely HTH domain, DNA biinding protein
152	C3a152	25.85	3	143	Anacy_5891	ALN Gene Pfam PDB	Type III-C specific	Type III-C specific. Likely N-ter. RRM (RNA recognition motif; unknown function
156	C3a156	28.1	3	330	NIES39_M01150	ALN Gene Pfam PDB	oxidoreductase	methylenetetrahydromethanopterin reductase
159	C3a159	27.06	3	304	Calkr_2554	ALN Gene Pfam PDB	methyl transferase	N-ter. methyl transferase domain
162	C3a162	40.43	3	181	Calni_1607	ALN Gene Pfam PDB	unknown	unknown structure-function
166	C3a166	32.1	3	181	Chy400_2477	ALN Gene Pfam PDB	poss. crRNA proc.	possible crRNA maturation ribonuclease, instead of Cas6
168	C3a168	31.1	3	374	MYO_4810	ALN Gene Pfam PDB	unknown	slr7083 in S.6803. Single k.o. for this gene. Belongs to CRISPR3.
173	Csx21	70	3	107	Adeg_0988	ALN Gene Pfam PDB	unknown	unknown structure-function
174	C3a174	74.3	3	309	Adeg_0798	ALN Gene Pfam PDB	nucleotidyl trans.	nucleotidyl transferase. Could be involved as the toxin in the Type IV toxin-antitoxin antiphage mechanism. See PMID: 24465005 for details.
178	C3a178	37.97	3	120	Fisuc_1555	ALN Gene Pfam PDB	putative invertase	putative transposase or invertase
181	C3a181	25.55	3	275	Kcr_0450	ALN Gene Pfam PDB	diadenylate cyclase	diadenylate cyclase (c-di-AMP synthetase), DisA, possible involved in signalling
186	C3a186	28.77	3	469	ANT_24470	ALN Gene Pfam PDB	C-3',4' desaturase	C-3',4' desaturase CrtD
187	C3a187	39	3	624	Syn7502_02851	ALN Gene Pfam PDB	NERD+UvrD	DNA/RNA helicase + (exo)nuclease at C-terminus
189	C3a189	50.73	3	1053	Hoch_1322	ALN Gene Pfam PDB	kinase	catalytic domain of bacterial serine/threonine kinases(STKs)
193	C3a193	43.78	3	1067	Thebr_0949	ALN Gene Pfam PDB	poss. alt. Cas3	looks like a variant of Cas3 for Type III
194	C3a194	26.83	3	477	TepRe1_0131	ALN Gene Pfam PDB	AA transporter	Amino acid transporter or permease
196	C3a196	46.29	3	96	Runsl_4349	ALN Gene Pfam PDB	unknown	unknown structure-function
198	C3a198	40.67	3	532	K649_15110	ALN Gene Pfam PDB	TPR-repeat	tetratricopeptide repeat
205	C3a205	67.5	3	387	MLP_11360	ALN Gene Pfam PDB	unknown	unknown structure-function
206	C3a206	29.39	3	535	B005_5542	ALN Gene Pfam PDB	TAP-like protein	TAP-like protein; family of peptidases and hydrolases
211	cas_RFas	51.67	3	187	Pogu_1163	ALN Gene Pfam PDB	unknown	unknown structure-function
212	C3a212	39.67	3	338	RoseRS_0371	ALN Gene Pfam PDB	SNc+LTD	N-ter. endonuclease domain with a C-ter. lamin tail domain (LTD)
214	C3a214	30.16	3	639	Rcas_3915	ALN Gene Pfam PDB	GlgB	1,4 alpha glucan-branching enzyme, GlgB
216	C3a216	25.6	3	77	SSA_1254	ALN Gene Pfam PDB	adaptation associated	associated with Type III systems that have an adaptation module. Shows sequence similarity with Cas1 in other bacteria.
222	C3a222	44	3	39	Vpar_1800	ALN Gene Pfam PDB	unknown	unknown structure-function
223	C3a223	43.33	3	84	YG5714_0635	ALN Gene Pfam PDB	unknown	unknown structure-function
227	PrimPol	36.73	3	577	Thein_1350	ALN Gene Pfam PDB	adaptation polymerase	N-ter. tetratricopeptide, C-ter. likely primase/polymerase domain. Linked to adaptation. Possible reverse transcriptase repair
230	C3a230	28.76	3	145	TT_P0114	ALN Gene Pfam PDB	RecX family protein	likely RecX recombination regulator