Rv2423 Resolved · high auto-curated

H37Rv Rv2423 · MTBC0 mtbc0_002580 · 348 aa · 2743865–2744911 (+) · RefSeq NP_216939.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationclass I SAM-dependent methyltransferase
Revised (this work)Class I SAM-dependent methyltransferase. Pfam: MTS (PF05175.21), Methyltransf_23 (PF13489.13), TehB (PF03848.21), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19).

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

Curated reference (UniProt)

UniProt P71925 TrEMBL · unreviewed · Evidence at protein level
UniProt nameMethyltransferase domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
eggNOG descriptionMethyltransferase type 12
Orthologous groupCOG2242

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 1.283 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (372) · 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
MTSPF05175.21 5.4e-05139–250 Methyltransferase small domain
Methyltransf_23PF13489.13 1.8e-07143–258 Methyltransferase domain
TehBPF03848.21 4.2e-05148–248 Tellurite resistance protein TehB
Methyltransf_25PF13649.13 3.8e-09150–245 Methyltransferase domain
Methyltransf_11PF08241.19 2.4e-05151–250 Methyltransferase domain

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

Closest characterised functional partner: Rv3435c (transmembrane protein), high confidence from genomic context alone (score 768 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2066 cobIJ bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase 965 943 coexpression:932 textmining:418
Rv2067c hyp hypothetical protein 776 777 ctx cooccurence:773
Rv3899c hyp hypothetical protein 772 772 ctx cooccurence:771
Rv3435c transmembrane protein 767 768 ctx cooccurence:767
Rv3166c hyp hypothetical protein 765 765 ctx cooccurence:756
Rv2079 hyp hypothetical protein 764 764 ctx cooccurence:763
Rv0048c membrane protein 752 753 ctx cooccurence:751
Rv3887c eccD2 ESX-2 secretion system protein EccD 747 747 ctx cooccurence:747
Rv0977 PE_PGRS16 PE-PGRS family protein PE_PGRS16 734 734 ctx cooccurence:734
Rv3843c transmembrane protein 722 723 ctx cooccurence:722
Rv2939 papA5 phthiocerol/phthiodiolone dimycocerosyl transferase 718 718 ctx cooccurence:718
Rv1359 transcriptional regulator 715 715 ctx cooccurence:715
Rv1904 hyp hypothetical protein 708 709 ctx cooccurence:708
Rv1795 eccD5 ESX-5 type VII secretion system protein EccD 706 706 ctx cooccurence:706
Rv2065 cobH precorrin-8X methylmutase 727 691 coexpression:673

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: hypothetical protein
  • MTBC0 PGAP product: class I SAM-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): MTS PF05175.21 (E=5e-05), Methyltransf_23 PF13489.13 (E=2e-07), TehB PF03848.21 (E=4e-05), Methyltransf_25 PF13649.13 (E=4e-09), Methyltransf_11 PF08241.19 (E=2e-05)
  • (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_216939.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MTS (PF05175.21), Methyltransf_23 (PF13489.13), TehB (PF03848.21), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19)
  • 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 COG2242
  • Curated reference: UniProt P71925 (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 — 80 functional partner(s); context anchor Rv3435c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002580|Rv2423|
MDNLPIESAESTRLAKAAMTRRFYTRSVVKGEITLPAVPSMIDEYVTMCAGLFAGVGRKFSDEELAHLRAVLQGQLAEAYAASQRSTIVISYNAPMGPTLHYQVRAQWRTVAQEYENWIATREPPLFGTEPDARVWALANEAADPTTHRVLEIGAGTGRNALALARRGHPVDVVEMTPKFADIIRSDAERDSLDVRVIMRDVFSTMDDLRQDYQLMVLSEVVPDFRTTQQLRNLFELAAQCLAPGARLVFNAFLANGDYAPDQAAREFGQQMYTGMCTRAEMSAAAAGLPLELVADDSVYDYEKTHLPPGAWPPTSWYADWIRGLDVFTTNVESCPIEMRWLVFQRRR