mutT4 Resolved · high auto-curated
H37Rv Rv3908 · MTBC0 mtbc0_004142 ·
248 aa · 4417701–4418447 (+) ·
RefSeq NP_218425.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mutator protein MutT |
|---|---|
| MTBC0 PGAP re-annotation | NUDIX hydrolase |
| Revised (this work) | NUDIX hydrolase. 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 |
P9WIX7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative mutator protein MutT4 |
| EC (curated) |
EC 3.6.1.-
|
| 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 (By similarity). In vitro has dATPase rather than 8-oxo-dGTPase activity. |
UniProt still lists this protein as Putative mutator protein MutT4; 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 name | mutT4 |
| eggNOG description | Belongs to the NUDIX hydrolase family |
| Orthologous group | COG0494 |
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 | 0.377 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
NUDIX | PF00293.35 | 2.8e-20 | 88–188 | NUDIX domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: murJ (peptidoglycan biosynthesis protein), high confidence from genomic context alone (score 884 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3909 hyp |
hypothetical protein | 939 | 888 ctx | neighborhood:881 textmining:478 |
Rv3910 murJ |
peptidoglycan biosynthesis protein | 884 | 884 ctx | neighborhood:881 |
Rv3912 rsmA |
anti-sigma-M factor RsmA | 812 | 805 ctx | neighborhood:804 |
Rv3911 sigM |
ECF RNA polymerase sigma factor SigM | 730 | 731 ctx | neighborhood:724 |
Rv3907c pcnA |
poly(A) polymerase PcnA | 689 | 689 ctx | neighborhood:679 |
Rv3906c hyp |
hypothetical protein | 674 | 674 ctx | neighborhood:669 |
Rv3913 trxB2 |
thioredoxin reductase | 625 | 607 ctx | neighborhood:549 |
Rv3914 trxC |
thioredoxin TrxC | 570 | 553 ctx | neighborhood:549 |
Rv3915 cwlM |
peptidoglycan hydrolase | 534 | 534 ctx | neighborhood:449 |
Rv3676 crp |
cAMP receptor protein | 436 | 427 | |
Rv2985 mutT1 |
8-oxo-dGTP diphosphatase | 427 | 212 | |
Rv2214c ephD |
oxidoreductase EphD | 570 | 93 | textmining:546 |
Rv2412 rpsT |
30S ribosomal protein S20 | 683 | 85 | textmining:668 |
Rv1316c ogt |
methylated-DNA--protein-cysteine methyltransferase | 821 | 76 | textmining:815 |
Rv0134 ephF |
epoxide hydrolase EphF | 531 | 76 | textmining:514 |
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: mutator protein MutT
- MTBC0 PGAP product: NUDIX hydrolase
- Pfam (hmmscan --cut_ga): NUDIX PF00293.35 (E=3e-20)
- (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_218425.1)
- 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 P9WIX7 (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 —
20 functional partner(s); context anchor
murJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004142|Rv3908|mutT4 MSDGEQAKSRRRRGRRRGRRAAATAENHMDAQPAGDATPTPATAKRSRSRSPRRGSTRMRTVHETSAGGLVIDGIDGPRDAQVAALIGRVDRRGRLLWSLPKGHIELGETAEQTAIREVAEETGIRGSVLAALGRIDYWFVTDGRRVHKTVHHYLMRFLGGELSDEDLEVAEVAWVPIRELPSRLAYADERRLAEVADELIDKLQSDGPAALPPLPPSSPRRRPQTHSRARHADDSAPGQHNGPGPGP