id: Q31PW6 gene_symbol: Synpcc7942_0873 locus_tag: Synpcc7942_0873 taxon: id: NCBITaxon:1140 label: Synechococcus elongatus PCC 7942 = FACHB-805 status: COMPLETE description: >- The KBase gene-annotate dashboard (Dark Protein Atlas) LLM call for S. elongatus CP088958.1_900 is "DUF4062 domain-containing protein, putative NACHT-family NTPase." (tier B). Its one GO term is GO:0017111 ribonucleoside triphosphate phosphatase activity (NTPase). The dashboard sequence is identical to PCC 7942 Synpcc7942_0873 (Q31PW6) over its full 362 residues, so the call is scored on Q31PW6. The DUF4062 part of the call is correct. The NTPase part is wrong. Its only basis is the STRING orthogroup label COG5635 ("Predicted NTPase, NACHT family domain"). The protein has no Walker A or Walker B motif and no NACHT or P-loop domain. Among DUF4062 proteins of 450 aa or less, only 1.3% carry a P-loop domain, compared with 86% of longer ones. The NTPase label therefore comes from multidomain DUF4062-NACHT relatives through the shared DUF4062 domain. The DUF4062 domain itself is a TIR-like NAD+ hydrolase (PMID:42146377), and the query keeps its conserved catalytic Glu (Glu83). The predicted activity is thus the wrong kind of hydrolase: an NADase, not an NTPase. The dashboard model did not see this evidence; the preprint postdates the evidence it was given. Dashboard verdict saved: wrong, the author's decision, concurring with a second dashboard reviewer who independently found no NTPase link in CDD or InterPro and read the predicted structure as a TIR domain plus a winged helix. An "overreach" verdict was considered, since the DUF4062 clause is correct and the NTPase extension is hedged and attributed to the COG5635 description, but was not adopted. On either reading the step too far is the same: a propagated orthogroup label became the headline of the annotation, although the STRING block supplying it states the matched homolog's annotation is withheld and is to be used as corroborating context rather than a primary annotation source, and although InterProScan on the query returned DUF4062 alone at 22.7% coverage. The GO term is a separate and harder error: the extractor turned a hedged family name into an unqualified activity term while recording that the trace had rejected ATPase activity. Corrected annotation: "DUF4062 (TIR-like) domain protein, probable NAD+ hydrolase; putative antiphage defence effector; no NTPase domain". source_documents: - genes/SYNE7/Synpcc7942_0873/Synpcc7942_0873-dashboard-prediction-evidence/dashboard_call.json - genes/SYNE7/Synpcc7942_0873/Synpcc7942_0873-dashboard-prediction-evidence/dashboard_page.txt - genes/SYNE7/Synpcc7942_0873/Synpcc7942_0873-bioinformatics/RESULTS.md references: - id: file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-dashboard-prediction-evidence/dashboard_page.txt title: gene-annotate dashboard review page for CP088958.1_900 findings: - statement: The NTPase assignment rests only on the STRING orthogroup label. supporting_text: >- Tier B: the identical STRING homolog provides a named NTPase-family assignment, supporting a qualified family-level annotation alongside the query's DUF4062 domain. - statement: The GO extractor mapped the word NTPase to GO:0017111. supporting_text: >- the term 'NTPase' directly maps to 'ribonucleoside triphosphate phosphatase activity' (GO:0017111) - id: file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-bioinformatics/RESULTS.md title: >- Synpcc7942_0873 (Q31PW6): NTPase motifs, DUF4062 domain context and the conserved Glu findings: - statement: The protein has no Walker A or Walker B motif. supporting_text: >- The query has no Walker A motif (GxxxxGK[ST]: 0 hits; relaxed [GA]xxxxGK[ST]: 0 hits; any GK[ST]: 0 hits) and no Walker B motif (hhhhD[DE]: 0 hits). - statement: COG5635's NTPase label describes the long multidomain members. supporting_text: >- COG5635 groups the short stand-alone DUF4062 proteins with these multidomain NACHT proteins, so its NTPase label describes the long members, not this one. - id: PMID:42146377 title: TIR-like NADases act in bacterial immunity and the RNA vault. findings: - statement: DUF4062 is a TIR-like NADase. supporting_text: >- we show that domain of unknown function 4062 (DUF4062) is a widespread family of TIR-like NADases that hydrolyze NAD+ to ADP-ribose and nicotinamide - statement: In human DUF4062 proteins the NTPase is a separate NACHT domain next to DUF4062. supporting_text: >- In human NWD1, NWD2, TEP1, and NPHP3, the DUF4062 domain lies adjacent to a NACHT ATPase predictions: - source_method: gene-annotate dashboard LLM annotation (Dark Protein Atlas) source_version: '2026-10-30 snapshot' predicted_term: id: GO:0017111 label: ribonucleoside triphosphate phosphatase activity predicted_term_type: GO_MF review: assessment: NPI confidence_score: 0 error_type: DOMAIN_ARCHITECTURE_MISMATCH summary: >- The prediction is refuted by the protein's own architecture. NTP hydrolysis by NACHT and other P-loop NTPases needs a Walker A (GxxxxGK[ST]) and a Walker B motif. Q31PW6 has neither, and it has no NACHT or P-loop domain. Its only domain is DUF4062 (6-146), followed by a coiled coil and an unassigned C-terminal region. The call took "NTPase" from the COG5635 orthogroup name. That name fits the long DUF4062-NACHT members, such as TEP1, where the NACHT ATPase is a separate domain next to DUF4062. P-loop domains occur in 86% of DUF4062 proteins over 450 aa but in only 1.3% of those of 450 aa or less. This is a multidomain donor's activity transferred through a shared domain that does not hydrolyse NTPs. The DUF4062 domain is instead a TIR-like NAD+ hydrolase (PMID:42146377), and Q31PW6 keeps its conserved Glu83. The term is absent from GOA, which has no annotations for Q31PW6. supported_by: - reference_id: file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-bioinformatics/RESULTS.md supporting_text: >- The query has no Walker A motif (GxxxxGK[ST]: 0 hits; relaxed [GA]xxxxGK[ST]: 0 hits; any GK[ST]: 0 hits) and no Walker B motif (hhhhD[DE]: 0 hits). - reference_id: file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-bioinformatics/RESULTS.md supporting_text: >- DUF4062 proteins of 450 aa or less, like this 362-aa protein, almost never carry an NTPase domain. - reference_id: PMID:42146377 supporting_text: >- In human NWD1, NWD2, TEP1, and NPHP3, the DUF4062 domain lies adjacent to a NACHT ATPase - reference_id: file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-dashboard-prediction-evidence/dashboard_page.txt supporting_text: >- Tier B: the identical STRING homolog provides a named NTPase-family assignment, supporting a qualified family-level annotation alongside the query's DUF4062 domain.