mutT2 Resolved · high auto-curated
H37Rv Rv1160 · MTBC0 mtbc0_001249 ·
141 aa · 1295036–1295461 (+) ·
RefSeq NP_215676.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 8-oxo-dGTP diphosphatase |
|---|---|
| MTBC0 PGAP re-annotation | 8-oxo-dGTP diphosphatase MutT |
| Revised (this work) | 8-oxo-dGTP diphosphatase MutT. Pfam: NUDIX (PF00293.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIY1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative 8-oxo-dGTP diphosphatase 2 |
| EC (curated) |
EC 3.6.1.55
|
| Curated function | May 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). In vitro has 8-oxo-dGTPase activity. |
UniProt still lists this protein as Putative 8-oxo-dGTP diphosphatase 2; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | mutT2 |
| eggNOG description | Belongs to the Nudix hydrolase family |
| Orthologous group | COG1051 |
| 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 | 0.745 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (664) · clonal |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
NUDIX | PF00293.35 | 9.4e-17 | 6–125 | NUDIX domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1159A (4a-hydroxytetrahydrobiopterin dehydratase), medium confidence from genomic context alone (score 669 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1159A |
4a-hydroxytetrahydrobiopterin dehydratase | 669 | 669 ctx | neighborhood:622 |
Rv1159 pimE |
polyprenol-phosphate-mannose-dependent alpha-(1-2)-phosphatidylinositol pentamannoside mannosyltransferase | 420 | 420 ctx | fusion:409 |
Rv1161 narG |
nitrate reductase subunit alpha | 469 | 405 ctx | neighborhood:404 |
Rv1164 narI |
nitrate reductase subunit gamma | 418 | 295 | |
Rv2924c fpg |
formamidopyrimidine-DNA glycosylase | 556 | 292 | |
Rv2043c pncA |
pyrazinamidase/nicotinamidase PncA | 413 | 291 | |
Rv3589 mutY |
A/G-specific adenine glycosylase | 490 | 118 | textmining:446 |
Rv3056 dinP |
DNA polymerase IV 2 | 403 | 112 | |
Rv0629c recD |
exonuclease V subunit alpha RecD | 496 | 109 | textmining:459 |
Rv1696 recN |
DNA repair protein RecN | 427 | 73 | textmining:408 |
Rv1629 polA |
DNA polymerase I | 432 | 72 | textmining:413 |
Rv1316c ogt |
methylated-DNA--protein-cysteine methyltransferase | 872 | 70 | textmining:868 |
Rv3908 mutT4 |
mutator protein MutT | 870 | 47 | textmining:870 |
Rv1210 tagA |
DNA-3-methyladenine glycosylase I TagA | 463 | 47 | textmining:460 |
Rv3731 ligC |
DNA ligase C | 433 | 47 | textmining:430 |
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
- Legacy H37Rv annotation: 8-oxo-dGTP diphosphatase
- MTBC0 PGAP product: 8-oxo-dGTP diphosphatase MutT
- Pfam (hmmscan --cut_ga): NUDIX PF00293.35 (E=9e-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_215676.1)
- 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
COG1051 - Curated reference: UniProt P9WIY1 (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 —
16 functional partner(s); context anchor
Rv1159A - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001249|Rv1160|mutT2 MLNQIVVAGAIVRGCTVLVAQRVRPPELAGRWELPGGKVAAGETERAALARELAEELGLEVADLAVGDRVGDDIALNGTTTLRAYRVHLLGGEPRARDHRALCWVTAAELHDVDWVPADRGWIADLARTLNGSAADVHRRC