Rv3322c Resolved · high auto-curated

H37Rv Rv3322c · MTBC0 - · 204 aa · 3708438–3709052 (-) · RefSeq YP_177958.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methyltransferase
MTBC0 PGAP re-annotation
Revised (this work)Methyltransferase. Pfam: Methyltransf_25 (PF13649.13).

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 L7N687 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible methyltransferase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
eggNOG descriptionmethyltransferase
Orthologous groupCOG2890

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 0.297 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (209) · 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)

PfamAccessioni-EvalueResiduesDescription
Methyltransf_25PF13649.13 9.5e-0851–140 Methyltransferase domain

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

Closest characterised functional partner: moaX (MoaD-MoaE fusion protein MoaX), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3323c moaX MoaD-MoaE fusion protein MoaX 885 884 ctx neighborhood:882
Rv3324A Rv3324A, len: 44 aa. Probable pseudogene moaB3,fragment of pterin-4-alpha-carbinolamine dehydratase,equivalent to C-terminus of MT3426|Q8VJ3 843 843 ctx neighborhood:801
Rv3324c moaC3 cyclic pyranopterin monophosphate synthase accessory protein 808 807 ctx neighborhood:801
Rv3320c vapC44 ribonuclease VapC44 566 567 ctx neighborhood:564
Rv3321c vapB44 antitoxin VapB44 565 565 ctx neighborhood:564
Rv3325 Rv3325, (MTV016.25), len: 108 aa. Putative Transposase for IS6110 (fragment). Identical to many other M. tuberculosis IS6110 transposase sub 559 559 ctx neighborhood:559
Rv3326 Probable transposase; Rv3326, (MTV016.26), len: 328 aa. Probable transposase for insertion element IS6110. Identical to many other M. tuberc 559 559 ctx neighborhood:559
Rv3327 transposase fusion protein 460 457 ctx neighborhood:449
Rv0341 iniB isoniazid inducible protein IniB 427 428
Rv2209 integral membrane protein 427 427 ctx cooccurence:422
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 406 406 ctx cooccurence:406
Rv1523 methyltransferase 887 166 textmining:871
Rv3448 eccD4 ESX-4 secretion system protein EccD4 481 156 textmining:411
Rv1895 zinc-binding alcohol dehydrogenase 765 139 textmining:739
Rv1522c mmpL12 transmembrane transport protein MmpL12 804 47 textmining:803

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): methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_25 PF13649.13 (E=1e-07)
  • (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 YP_177958.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_25 (PF13649.13)
  • 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 COG2890
  • Curated reference: UniProt L7N687 (TrEMBL, unreviewed; 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 — 15 functional partner(s); context anchor moaX
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3322c|
MSVQTDPALREHPNRVDWNARYERAGSAHAPFAPVPWLADVLRAGVPDGPVLELASGRSGTALALAAHGRQVTAIDVSDVALLQLDSEAVRRGVADRLNLVQADLGCWEPGETRFALVLSRLFWDAAIFHRACEAVMPGGVLAWESLALSGAEAGTASAKRRVKPGEPACLLPADFTVVHEGQGNCDSAPSRIMIARRSPLPGA