rsmD Resolved · high auto-curated

H37Rv Rv2966c · MTBC0 mtbc0_003150 · 188 aa · 3340076–3340642 (-) · RefSeq NP_217482.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methyltransferase
MTBC0 PGAP re-annotation16S rRNA (guanine(966)-N(2))-methyltransferase RsmD
Revised (this work)16S rRNA (guanine(966)-N(2))-methyltransferase RsmD. Pfam: Cons_hypoth95 (PF03602.22), MTS (PF05175.21).

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

Curated reference (UniProt)

UniProt I6XFS7 SwissProt · reviewed · Evidence at protein level
UniProt nameRNA/DNA methyltransferase Rv2966c
EC (curated) EC 2.1.1.-, EC 2.1.1.171
Curated functionSAM-dependent methyltransferase that binds both to RNA and DNA. Specifically methylates the guanine in position 966 of 16S rRNA in the 30S particle. In addition, can methylate and modulate host cellular DNA within an infected mammalian cell, altering the host epigenetic machinery. Binds to specific host DNA sequences and methylates cytosines predominantly in a non-CpG context.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namersmD
eggNOG descriptionMethyltransferase
Orthologous groupCOG0742
EC number EC 2.1.1.171
KEGG orthology K08316

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (156) · 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
Cons_hypoth95PF03602.22 2.1e-462–180 Conserved hypothetical protein 95
MTSPF05175.21 3.9e-0644–135 Methyltransferase small domain

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

Closest characterised functional partner: kdtB (phosphopantetheine adenylyltransferase), high confidence from genomic context alone (score 923 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2965c kdtB phosphopantetheine adenylyltransferase 953 923 ctx neighborhood:636 coexpression:682 textmining:422
Rv2967c pca pyruvate carboxylase 778 752 ctx neighborhood:737
Rv3922c yidD membrane protein insertion efficiency factor 700 695 coexpression:685
Rv2968c integral membrane protein 693 694 ctx neighborhood:689
Rv2969c hyp hypothetical protein 694 682 ctx neighborhood:680
Rv2970c lipN lipase/esterase LipN 675 675 ctx neighborhood:670
Rv1713 engA GTPase Der 513 513
Rv3923c rnpA ribonuclease P protein component 478 479 coexpression:477
Rv2902c rnhB ribonuclease HII 474 475
Rv1225c hyp hypothetical protein 412 413 coexpression:402
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 422 412
Rv3781 rfbE O-antigen/lipopolysaccharide ABC transporter ATP-binding protein RfbE 410 411 coexpression:411
Rv1712 cmk cytidylate kinase 408 409
Rv1692 phosphatase 408 409
Rv2424c transposase 407 407

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: methyltransferase
  • MTBC0 PGAP product: 16S rRNA (guanine(966)-N(2))-methyltransferase RsmD
  • Pfam (hmmscan --cut_ga): Cons_hypoth95 PF03602.22 (E=2e-46), MTS PF05175.21 (E=4e-06)
  • (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_217482.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cons_hypoth95 (PF03602.22), MTS (PF05175.21)
  • 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 COG0742
  • Curated reference: UniProt I6XFS7 (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 — 23 functional partner(s); context anchor kdtB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003150|Rv2966c|rsmD
MTRIIGGVAGGRRIAVPPRGTRPTTDRVRESLFNIVTARRDLTGLAVLDLYAGSGALGLEALSRGAASVLFVESDQRSAAVIARNIEALGLSGATLRRGAVAAVVAAGTTSPVDLVLADPPYNVDSADVDAILAALGTNGWTREGTVAVVERATTCAPLTWPEGWRRWPQRVYGDTRLELAERLFANV