Rv2675c Resolved · high auto-curated
H37Rv Rv2675c · MTBC0 mtbc0_002849 ·
250 aa · 3013497–3014249 (-) ·
RefSeq NP_217191.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | class I SAM-dependent methyltransferase |
| Revised (this work) | Class I SAM-dependent methyltransferase. Pfam: Methyltransf_23 (PF13489.13), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19), Methyltransf_12 (PF08242.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y1G8
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Methyltransferase domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Thiopurine S-methyltransferase (TPMT) |
| Orthologous group | COG0500 |
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 | 0.443 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.72% of strains (1048) · 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 |
|---|---|---|---|---|
Methyltransf_23 | PF13489.13 | 8.7e-07 | 43–153 | Methyltransferase domain |
Methyltransf_31 | PF13847.13 | 7.3e-15 | 53–158 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 1.7e-15 | 54–149 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 4.9e-13 | 55–153 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 1.9e-07 | 55–152 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemE (uroporphyrinogen decarboxylase), high confidence from genomic context alone (score 820 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2678c hemE |
uroporphyrinogen decarboxylase | 828 | 820 ctx | neighborhood:773 |
Rv2676c hemQ hyp |
hypothetical protein | 787 | 786 ctx | neighborhood:773 |
Rv2677c hemY |
protoporphyrinogen oxidase | 786 | 786 ctx | neighborhood:776 |
Rv2679 echA15 |
enoyl-CoA hydratase EchA15 | 566 | 566 ctx | neighborhood:560 |
Rv2751 hyp |
hypothetical protein | 520 | 521 ctx | cooccurence:510 |
Rv3707c hyp |
hypothetical protein | 443 | 444 ctx | cooccurence:440 |
Rv2743c hyp |
hypothetical protein | 401 | 401 |
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): Methyltransf_23 PF13489.13 (E=9e-07), Methyltransf_31 PF13847.13 (E=7e-15), Methyltransf_25 PF13649.13 (E=2e-15), Methyltransf_11 PF08241.19 (E=5e-13), Methyltransf_12 PF08242.19 (E=2e-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 NP_217191.1)
- Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_23 (PF13489.13), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19), Methyltransf_12 (PF08242.19)
- 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
COG0500 - Curated reference: UniProt I6Y1G8 (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 —
7 functional partner(s); context anchor
hemE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002849|Rv2675c| MTAQFDPADPTRFEEMYRDDRVAHGLPAATPWDIGGPQPVVQQLVALGAIRGEVLDPGTGPGHHAIYYAAKGYAATGIDGSVAAIERARDNARKAGVSVNFQVGDATTLDGLDGRFDTVVDCAFYHTFSTAPELQRCYVRALRRASKPGARLYMFEFGEHNVNGFSMPRSLSEDDFRQVLPVGGWEITYLGTTTYQVNLSVEALELMAARNPDMADQVRCVLERFRAIKPWLVGGRVHAPFWEVHATRVD