Rv2258c Resolved · high auto-curated
H37Rv Rv2258c · MTBC0 mtbc0_002401 ·
353 aa · 2556996–2558057 (-) ·
RefSeq NP_216774.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | class I SAM-dependent methyltransferase |
| Revised (this work) | Class I SAM-dependent methyltransferase. Pfam: WHD_Rv2258c (PF21320.4), Methyltransf_23 (PF13489.13), MTS (PF05175.21), PrmA (PF06325.20), PCMT (PF01135.26), Methyltransf_31 (PF13847.13), Ubie_methyltran (PF01209.25), Methyltransf_2 (PF00891.25), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), 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 |
O53532
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | S-adenosylmethionine-dependent methyltransferase Rv2258c |
| EC (curated) |
EC 2.1.1.-
|
| Curated function | Probable methyltransferase that may target bulky nonpolar molecules with aromatic rings. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| eggNOG description | Methyltransferase |
| Orthologous group | COG2230 |
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 | 0.89 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 8 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (657) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
WHD_Rv2258c | PF21320.4 | 9.8e-37 | 22–96 | Rv2258c-like winged HTH domain |
Methyltransf_23 | PF13489.13 | 1.6e-16 | 160–335 | Methyltransferase domain |
MTS | PF05175.21 | 3.9e-07 | 161–275 | Methyltransferase small domain |
PrmA | PF06325.20 | 1.3e-05 | 167–273 | Ribosomal protein L11 methyltransferase (PrmA) |
PCMT | PF01135.26 | 1.7e-05 | 169–281 | Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT) |
Methyltransf_31 | PF13847.13 | 5.2e-23 | 170–285 | Methyltransferase domain |
Ubie_methyltran | PF01209.25 | 5.1e-08 | 170–276 | ubiE/COQ5 methyltransferase family |
Methyltransf_2 | PF00891.25 | 2.3e-05 | 170–281 | O-methyltransferase domain |
Methyltransf_25 | PF13649.13 | 9.7e-19 | 175–269 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 2.9e-18 | 177–271 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 7.9e-16 | 177–272 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mscR (S-nitrosomycothiol reductase MscR), high confidence from genomic context alone (score 706 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2257c hyp |
hypothetical protein | 878 | 879 ctx | neighborhood:872 |
Rv2259 mscR |
S-nitrosomycothiol reductase MscR | 706 | 706 ctx | neighborhood:692 |
Rv2260 hyp |
hypothetical protein | 705 | 705 ctx | neighborhood:692 |
Rv2256c hyp |
hypothetical protein | 513 | 514 ctx | neighborhood:511 |
Rv3711c dnaQ |
DNA polymerase III subunit epsilon | 580 | 79 | textmining:564 |
Rv0707 rpsC |
30S ribosomal protein S3 | 688 | 58 | textmining:683 |
Rv0704 rplB |
50S ribosomal protein L2 | 518 | 58 | textmining:510 |
Rv2890c rpsB |
30S ribosomal protein S2 | 755 | 47 | textmining:754 |
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: transcriptional regulator
- MTBC0 PGAP product: class I SAM-dependent methyltransferase
- Pfam (hmmscan --cut_ga): WHD_Rv2258c PF21320.4 (E=1e-36), Methyltransf_23 PF13489.13 (E=2e-16), MTS PF05175.21 (E=4e-07), PrmA PF06325.20 (E=1e-05), PCMT PF01135.26 (E=2e-05), Methyltransf_31 PF13847.13 (E=5e-23), Ubie_methyltran PF01209.25 (E=5e-08), Methyltransf_2 PF00891.25 (E=2e-05), Methyltransf_25 PF13649.13 (E=1e-18), Methyltransf_12 PF08242.19 (E=3e-18), Methyltransf_11 PF08241.19 (E=8e-16)
- (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_216774.1)
- Domains: Pfam-A via hmmscan --cut_ga — WHD_Rv2258c (PF21320.4), Methyltransf_23 (PF13489.13), MTS (PF05175.21), PrmA (PF06325.20), PCMT (PF01135.26), Methyltransf_31 (PF13847.13), Ubie_methyltran (PF01209.25), Methyltransf_2 (PF00891.25), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), 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
COG2230 - Curated reference: UniProt O53532 (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 —
8 functional partner(s); context anchor
mscR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002401|Rv2258c| MSGALETTEEFGNRFVAAIDSAGLAILVSVGHQTGLLDTMAGLPPATSMEIAEAAGLEERYVREWLGGMTTGQIVEYDAGSSTYSLPAHRAGMLTRAAGPDNLAVIAQFVSLLGEVEQKVIRCFREGGGVPYSEYPRFHKLMAEMSGMVFDAALIDVVLPLVDGLPDRLRSGADVADFGCGSGRAVKLMAQAFGASRFTGIDFSDEAVAAGTEEAARLGLANATFERHDLAELDKVGAYDVITVFDAIHDQAQPARVLQNIYRALRPGGVLLMVDIKASSQLEDNVGVPLSTYLYTTSLMHCMTVSLALDGAGLGTVWGRQLATSMLADAGFTDVTVAEIESDVLNNYYIARK