| Feature | Squid ADAR2 (sqADAR2a/b; C1JAR3 corresponds to sqADAR2b) | Human ADAR2 (ADARB1) | ADAT2 / TadA |
|---|---|---|---|
| Domain architecture | sqADAR2b: 2 dsRBDs + C-terminal deaminase domain; sqADAR2a: same plus optional extra dsRBD (3 total) (pqac-00000001, pqac-00000002, pqac-00000013, pqac-00000014) | Canonical ADAR architecture: 2 dsRBDs + C-terminal catalytic deaminase domain (pqac-00000005, pqac-00000009) | ADAT2/3: tRNA-editing heterodimer; ADAT2 catalytic subunit lacks dsRBDs; TadA is a prokaryotic tRNA deaminase without dsRBDs (pqac-00000005, pqac-00000006, pqac-00000008) |
| Zinc-coordinating residues (H, C, C) | Conserved and intact: H458, C516, C580 in squid ADAR2; experimentally recognized as catalytic metal ligands (pqac-00000013) | Conserved ADAR2 ligands: H394, C451, C516 (pqac-00000010, pqac-00000012) | Similar catalytic core in the ADAT/TadA lineage, but in a tRNA-editing scaffold/subfamily rather than dsRNA-binding ADAR scaffold (pqac-00000004, pqac-00000006, pqac-00000012) |
| Catalytic glutamate | Conserved and intact: E460 proton-shuttling residue in squid ADAR2 (pqac-00000013) | E396 catalytic glutamate in human ADAR2 (pqac-00000010, pqac-00000012) | Conserved HxE-type catalytic glutamate is typical of ADAT/TadA chemistry, but supports tRNA deamination rather than ADAR dsRNA editing (pqac-00000004, pqac-00000006) |
| IP6 binding | 22/24 human ADAR2 IP6-contacting positions conserved in squid ADAR2; consistent with ADAR-family catalytic-domain architecture (pqac-00000013) | IP6-binding cavity present and important for ADAR catalytic-domain stability/activity; effectively the ADAR reference state (24/24 in human structure context) (pqac-00000004, pqac-00000010) | ADAT2/3 lacks the ADAR1/ADAR2 IP6-binding cavity; ADAT2/TadA therefore differs structurally from ADARs at this feature (pqac-00000004, pqac-00000010) |
| Substrate specificity | Directly shown active on duplex RNA / mRNA substrates, including squid K+ channel transcripts sqKv1.1A and sqKv1.2A; no evidence of tRNA-specific activity (pqac-00000001, pqac-00000002, pqac-00000014, pqac-00000017, pqac-00000020) | Double-stranded RNA adenosine deaminase acting on dsRNA/mRNA substrates (pqac-00000009, pqac-00000010) | tRNA-specific adenosine deaminase activity at wobble position A34 or related anticodon-loop targets (pqac-00000005, pqac-00000006, pqac-00000008, pqac-00000009) |
| Sequence identity to human ADAR2 | Deaminase domain shares ~61% identity with human ADAR2; dsRBDs ~80% identity, strongly supporting ADAR2 orthology/subfamily placement (pqac-00000013) | Reference protein | Not reported as close ADAR2 orthologs; treated as distinct ancestral/sibling tRNA-editing subfamily rather than ADAR2 orthologs (pqac-00000005, pqac-00000008) |
| Catalytic activity demonstrated | Yes. Recombinant sqADAR2a and sqADAR2b are active on duplex RNA in vitro; sqADAR2a edits more sites than sqADAR2b; in vivo editing also documented in squid nervous system (pqac-00000014, pqac-00000015, pqac-00000017, pqac-00000019, pqac-00000020) | Yes. Human ADAR2 is the structurally and biochemically characterized dsRNA-editing reference enzyme (pqac-00000010, pqac-00000012) | Yes for tRNA editing, but on tRNA substrates and in a different subfamily/context (pqac-00000005, pqac-00000006, pqac-00000008) |
| Failure mode classification | Seed GO term GO:0008251 is a wrong-subfamily / sibling-activity assignment: squid ADAR2 is an ADAR-family dsRNA editor, not an ADAT-family tRNA editor (pqac-00000001, pqac-00000004, pqac-00000008, pqac-00000009) | Not applicable | Correct family for GO:0008251-like tRNA-editing functions; contrasts with squid ADAR2 and localizes the propagation error (pqac-00000005, pqac-00000008, pqac-00000009) |


*Table: This table compares squid ADAR2 with human ADAR2 and ADAT/tRNA deaminases across architecture, catalytic residues, cofactor features, and substrate specificity. It highlights that squid ADAR2 is clearly a dsRNA-editing ADAR enzyme and that the propagated tRNA-specific GO term reflects a wrong-subfamily sibling-activity error.*