Synpcc7942_0873

UniProt ID: Q31PW6
Organism: Synechococcus elongatus PCC 7942 = FACHB-805
Review Status: COMPLETE
Aliases:
CP088958.1_900
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Gene Description

Synpcc7942_0873 is an uncharacterized 362-residue protein, predicted cytoplasmic. It has an N-terminal DUF4062 domain (PF13271, residues 6-146), a predicted coiled coil (170-197) and a C-terminal region of about 165 residues with no InterPro or Pfam match. DUF4062 is a TIR-like NAD+ hydrolase that converts NAD+ to ADP-ribose and nicotinamide and needs a conserved catalytic Glu (PMID:42146377, a 2026 preprint). Bacterial members such as Klebsiella Swarozyc are antiphage defence proteins built from the TIR-like domain, helical stalks and a C-terminal auxiliary domain. They are activated by the phage portal and kill the infected cell by depleting NAD+ (abortive infection). Synpcc7942_0873 has the same short layout and keeps the family's conserved Glu as Glu83, in GLSYTEKEY, at the Pfam HMM position of human TEP1 Glu1008, which TEP1 needs for activity. It is therefore a probable NAD+ nucleosidase. This has not been tested, and not every DUF4062 protein is active. Its trigger, its partners and any role in phage defence are unknown. The protein has no P-loop NTPase domain and no Walker A or Walker B motif.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003953 NAD+ nucleosidase activity
ISS
PMID:42146377
TIR-like NADases act in bacterial immunity and the RNA vault... 		NEW
Summary: Synpcc7942_0873 is a probable NAD+ nucleosidase. This is inferred from its DUF4062 TIR-like domain and its retention of the family's conserved catalytic Glu.
Reason: DUF4062 domains of bacterial Swarozyc and human TEP1 hydrolyse NAD+ to ADP-ribose and nicotinamide, and the activity needs a conserved active-site Glu (E97 and E1008; PMID:42146377). The query's DUF4062 domain (Pfam hit 6-146, i-Evalue 1.4e-53) has Glu83 at the family's most conserved Glu position: Pfam HMM state 78, consensus E, and identical in 93% of 375 short bacterial homologs. TEP1 E1008 maps to the same HMM state, in a matching S-x-T-E-x-E motif. The protein also has the short Swarozyc-like layout of TIR-like domain, coiled-coil stalk and C-terminal region. Two points limit the inference. The activity was shown for distant relatives in a preprint, not for this protein. And not every DUF4062 protein is active: human NWD1, NWD2 and NPHP3 were inactive. NAD+ nucleosidase activity (NAD+ + H2O = ADP-ribose + nicotinamide) matches the reported products. No cyclic ADP-ribose products were reported, so the cADPR-generating child term is not used.
Supporting Evidence:
PMID:42146377
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
PMID:42146377
Sequence alignments identified a conserved Glu as a likely catalytic residue, corresponding to the known catalytic site of TIR NADases
file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-bioinformatics/RESULTS.md
Glu83 sits at match state 78, whose consensus is an uppercase (highly conserved) E with emission probability P(E) = 0.602, the highest of any query Glu.
file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-bioinformatics/RESULTS.md
TEP1 E1008 also maps to match state 78, the state of the query's Glu83.

Core Functions

Probable TIR-like NAD+ hydrolase (DUF4062 domain, conserved catalytic Glu83). By analogy with bacterial Swarozyc, it may be a signal-activated NAD+-depleting effector, possibly an antiphage abortive-infection protein. The activating signal and the defence role are untested.

Molecular Function:
NAD+ nucleosidase activity
Supporting Evidence:
  • PMID:42146377
    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
  • file:SYNE7/Synpcc7942_0873/Synpcc7942_0873-bioinformatics/RESULTS.md
    Glu83 is identical in 93% of them, the third most conserved position overall

References

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Suggested Questions for Experts

Q: Does purified Synpcc7942_0873 hydrolyse NAD+ to ADP-ribose and nicotinamide, and does the Glu83Ala mutant abolish this?

Q: Does Synpcc7942_0873 defend S. elongatus against cyanophage, and is it activated by a phage portal protein as Swarozyc is?

Q: Is Synpcc7942_0873 NAD+-specific, or does it also hydrolyse NADP+ as TEP1 does?

Q: Do the neighbouring SNF2/RAD54 helicase and UvrC-like endonuclease genes form a defence island with Synpcc7942_0873?

Suggested Experiments

Experiment: Express and purify Synpcc7942_0873 and its E83A mutant, incubate with NAD+ and NADP+, and analyse products by HPLC, alone and in oligomerizing conditions or with candidate cyanophage portal proteins.

Type: in vitro NADase assay with active-site mutant

Experiment: Express Synpcc7942_0873 (WT and E83A) in a heterologous host or S. elongatus and test for phage defence and NAD+ depletion upon infection.

Type: phage challenge / abortive infection assay

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

gene-annotate dashboard LLM annotation (Dark Protein Atlas) External predictions

View prediction review YAML · Synpcc7942_0873-dashboard-predictions-review.yaml · Review status: COMPLETE

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

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0017111 ribonucleoside triphosphate phosphatase activity GO_MF
NPI — Nonparalog incorrect Review score: 0/2
Prediction method: gene-annotate dashboard LLM annotation (Dark Protein Atlas) · Version: 2026-10-30 snapshot
DOMAIN ARCHITECTURE MISMATCH
Review rationale: 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.
Supporting Evidence:

Deep Research

Claude Code

(Synpcc7942_0873-deep-research-claude-code.md)

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📚 Additional Documentation

Notes

(Synpcc7942_0873-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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