REGION 1..82 HD domain (ECO:0000305|PubMed:27105119) andDOMAIN 509..647 GGDEF (PROSITE-ProRule:PRU00095, ECO:0000305|PubMed:27105119).This is the orthologue in which cyclic oligoadenylate synthesis was demonstrated.
It must not be conflated with Q53W19 (THET8, Thermus thermophilus HB8), where the same
activity is a curator inference coded ECO:0000305. The two reviews cite each organism's
own work; the mnemonics STRTR and THET8 are easy to transpose and the species names
differ by one letter.
The activity is under two layers of control, both demonstrated in this organism. Temporal:
PMID:27105119. Self/non-self:
PMID:27105119. And spatial:
PMID:27105119.
UniProt adds, with experimental evidence from the same paper, that the activity requires
Mn2+, Co2+ or Ni2+ and is not supported by Mg2+, Ca2+ or Zn2+, that it is inhibited by
EDTA, and that activity on dsDNA is low and not stimulated by the complex. The
single-strand specificity plus the demonstrated digestion of circular as well as linear
ssDNA (ECO:0000250|UniProtKB:B6YWB8) is what makes both an endonuclease and an
exonuclease term applicable.
UniProt records for this entry, with ECO:0000269|PubMed:28663439 throughout:
FUNCTION: When associated with the ternary Csm effector complex ... synthesizes cyclic
oligoadenylates (cOA) from ATP, producing cyclic triadenylate (cA3) up to cyclic
hexaadenylate (cA6), which is the active cOA. The enzyme is also able to cyclize pppA3
up to pppA6. ... Synthesis of cOA can occur with AMP plus ATP, 2'dATP or 3'dATP (but no
other nucleotides), and requires a free 3'-OH ribose moiety.CATALYTIC ACTIVITY: Reaction=6 ATP = cyclic hexaadenylate + 6 diphosphate;
Xref=Rhea:RHEA:58276 ... Evidence={ECO:0000269|PubMed:28663439}
The free-3'-OH requirement is itself the chemical signature that distinguishes this
reaction from the metazoan 2'-5'-OAS reaction, which links the 2'-OH.
UniProt's MUTAGEN features (both ECO:0000269|PubMed:27105119 and
ECO:0000269|PubMed:28663439) are the cleanest evidence that one protein carries two
independent catalytic centres:
MUTAGEN 16: D->A: Dramatically decreased ssDNase activity. Wild-type synthesis of cOA.
MUTAGEN 575..576: DD->AA: Wild-type ssDNase activity. No synthesis of cOA.
That reciprocal pattern is why this review records two separate core functions rather
than one composite activity.
UniProt SUBUNIT, ECO:0000269 from all three papers: "Part of the Csm effector complex that
includes at least Cas10(1), Csm2(3), Csm3(5), Csm4(1), Csm5(1) and mature crRNA", with
Cas10 and Csm4 capping one end of the Csm3 filament.
Note what that last result does and does not show: it establishes that the system
restricts phage, and it attributes the restriction in that assay to the Csm3 RNase. It is
not a demonstration that Cas10 is required for immunity in vivo, so GO:0051607 is coded
IC here rather than IMP.
Identical to the Thermus case and argued at length in
genes/THET8/cas10/cas10-notes.md: GO has no term for cyclic oligoadenylate synthase
activity, GO:0001730 2'-5'-oligoadenylate synthetase activity is the metazoan OAS enzyme
and is the wrong term, and the right placement is as a sibling of GO:0106408 diadenylate
cyclase activity and GO:0052621 diguanylate cyclase activity under GO:0016779
nucleotidyltransferase activity. The same proposed_new_terms entry appears in both cas10
reviews; this one carries the experimental support (ECO:0000269 / IDA), the Thermus one the
inferred support (ECO:0000305 / ISS).
NEW. Unlike the Thermus entry these are coded IDA, because