trmU Resolved · high auto-curated
H37Rv Rv3024c · MTBC0 mtbc0_003215 ·
367 aa · 3404095–3405198 (-) ·
RefSeq NP_217540.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | tRNA-specific 2-thiouridylase |
|---|---|
| MTBC0 PGAP re-annotation | tRNA 2-thiouridine(34) synthase MnmA |
| Revised (this work) | TRNA 2-thiouridine(34) synthase MnmA. Pfam: tRNA_Me_trans (PF03054.23), ThiI (PF02568.21), tRNA_Me_trans_M (PF20259.4), tRNA_Me_trans_C (PF20258.5). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJS5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | tRNA-specific 2-thiouridylase MnmA |
| EC (curated) |
EC 2.8.1.13
|
| Curated function | Catalyzes the 2-thiolation of uridine at the wobble position (U34) of tRNA, leading to the formation of s(2)U34. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | mnmA |
| eggNOG description | Catalyzes the 2-thiolation of uridine at the wobble position (U34) of tRNA, leading to the formation of s(2)U34 |
| Orthologous group | COG0482 |
| EC number |
EC 2.8.1.13
|
| KEGG orthology |
K00566
|
| KEGG pathways |
map04122
|
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 | 1.452 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 8 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 |
|---|---|---|---|---|
tRNA_Me_trans | PF03054.23 | 6.5e-76 | 1–196 | tRNA methyl transferase HUP domain |
ThiI | PF02568.21 | 1.8e-04 | 2–34 | Thiamine biosynthesis protein (ThiI) |
tRNA_Me_trans_M | PF20259.4 | 1.6e-20 | 201–268 | tRNA methyl transferase PRC-barrel domain |
tRNA_Me_trans_C | PF20258.5 | 5.9e-17 | 275–353 | Aminomethyltransferase beta-barrel domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: iscS (cysteine desulfurase), high confidence from genomic context alone (score 939 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3025c iscS |
cysteine desulfurase | 953 | 939 ctx | neighborhood:881 coexpression:406 |
Rv3027c |
GCN5-like N-acetyltransferase | 776 | 776 ctx | neighborhood:775 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 683 | 683 ctx | neighborhood:680 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 678 | 679 | coexpression:659 |
Rv3026c hyp |
hypothetical protein | 625 | 625 ctx | neighborhood:623 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 582 | 572 ctx | neighborhood:568 |
Rv1901 cinA |
competence damage-inducible protein CinA | 517 | 518 | |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 683 | 486 | coexpression:401 textmining:410 |
Rv1334 mec |
[CysO | 473 | 473 | |
Rv3023c |
transposase | 473 | 473 ctx | neighborhood:468 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 477 | 453 | |
Rv1691 hyp |
hypothetical protein | 451 | 452 | database:420 |
Rv3923c rnpA |
ribonuclease P protein component | 518 | 446 | coexpression:414 |
Rv2267c stf3 hyp |
hypothetical protein | 446 | 446 | database:420 |
Rv3529c hyp |
hypothetical protein | 446 | 446 | database:420 |
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: tRNA-specific 2-thiouridylase
- MTBC0 PGAP product: tRNA 2-thiouridine(34) synthase MnmA
- Pfam (hmmscan --cut_ga): tRNA_Me_trans PF03054.23 (E=7e-76), ThiI PF02568.21 (E=2e-04), tRNA_Me_trans_M PF20259.4 (E=2e-20), tRNA_Me_trans_C PF20258.5 (E=6e-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_217540.1)
- Domains: Pfam-A via hmmscan --cut_ga — tRNA_Me_trans (PF03054.23), ThiI (PF02568.21), tRNA_Me_trans_M (PF20259.4), tRNA_Me_trans_C (PF20258.5)
- 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
COG0482 - Curated reference: UniProt P9WJS5 (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 —
33 functional partner(s); context anchor
iscS - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003215|Rv3024c|trmU MKVLAAMSGGVDSSVAAARMVDAGHEVVGVHMALSTAPGTLRTGSRGCCSKEDAADARRVADVLGIPFYVWDFAEKFKEDVINDFVSSYARGETPNPCVRCNQQIKFAALSARAVALGFDTVATGHYARLSGGRLRRAVDRDKDQSYVLAVLTAQQLRHAAFPIGDTPKRQIRAEAARRGLAVANKPDSHDICFIPSGNTKAFLGERIGVRRGVVVDADGVVLASHDGVHGFTIGQRRGLGIAGPGPNGRPRYVTAIDADTATVHVGDVTDLDVQTLTGRAPVFTAGAAPSGPVDCVVQVRAHGETVSAVAELIGDALFVQLHAPLRGVARGQTLVLYRPDPAGDEVLGSATIAGASGLSTGGNPGA