mutT3 Resolved · high auto-curated

H37Rv Rv0413 · MTBC0 - · 217 aa · 499713–500366 (+) · RefSeq NP_214927.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)8-oxo-dGTP diphosphatase
MTBC0 PGAP re-annotation
Revised (this work)8-oxo-dGTP diphosphatase. Pfam: NUDIX (PF00293.35).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WIX9 SwissProt · reviewed · Evidence at protein level
UniProt namePutative 8-oxo-dGTP diphosphatase 3
EC (curated) EC 3.6.1.55
Curated functionMay be involved in the GO system responsible for removing an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine, 8-oxo-dGTP) from DNA and the nucleotide pool. 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with almost equal efficiency thus leading to A.T to G.C transversions. MutT specifically degrades 8-oxo-dGTP to the monophosphate (By similarity).

UniProt still lists this protein as Putative 8-oxo-dGTP diphosphatase 3; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namemutT3
eggNOG descriptionBelongs to the NUDIX hydrolase family
Orthologous groupCOG0494
EC number EC 3.6.1.55
KEGG orthology K03574

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 1.45 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 missense, 0 nonsense, 0 frameshift

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
NUDIXPF00293.35 1.9e-1745–155 NUDIX domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: glnH (glutamine-binding lipoprotein GlnH), medium confidence from genomic context alone (score 644 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3282 hyp hypothetical protein 823 823 ctx fusion:809
Rv0411c glnH glutamine-binding lipoprotein GlnH 644 644 ctx neighborhood:635
Rv0410c pknG serine/threonine-protein kinase PknG 738 640 ctx neighborhood:635
Rv0412c glnX membrane protein 640 640 ctx neighborhood:635
Rv0531 membrane protein 456 457 ctx cooccurence:406
Rv0904c accD3 acetyl-CoAcarboxylase carboxyl transferase subunit beta 427 345
Rv3251c rubA rubredoxin RubA 494 46 textmining:492
Rv0097 oxidoreductase 411 44 textmining:410

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): 8-oxo-dGTP diphosphatase
  • Pfam (hmmscan --cut_ga): NUDIX PF00293.35 (E=2e-17)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_214927.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NUDIX (PF00293.35)
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG COG0494
  • Curated reference: UniProt P9WIX9 (SwissProt, reviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 8 functional partner(s); context anchor glnH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0413|mutT3
MPSCPPAYSEQVRGDGDGWVVSDSGVAYWGRYGAAGLLLRAPRPDGTPAVLLQHRALWSHQGGTWGLPGGARDSHETPEQTAVRESSEEAGLSAERLEVRATVVTAEVCGVDDTHWTYTTVVADAGELLDTVPNRESAELRWVAENEVADLPLHPGFAASWQRLRTAPATVPLARCDERRQRLPRTIQIEAGVFLWCTPGDADQAPSPLGRRISSLL