Rv3699 Resolved · high auto-curated
H37Rv Rv3699 · MTBC0 mtbc0_003921 ·
233 aa · 4165992–4166693 (+) ·
RefSeq NP_218216.1
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: TPMT (PF05724.18), 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 |
O69667
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2-heptyl-1-hydroxyquinolin-4(1H)-one methyltransferase |
| EC (curated) |
EC 2.1.1.374
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Methyltransferase |
| 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 6 missense, 0 nonsense, 0 frameshift |
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 |
|---|---|---|---|---|
TPMT | PF05724.18 | 1.2e-13 | 22–186 | Thiopurine S-methyltransferase (TPMT) |
Methyltransf_23 | PF13489.13 | 2.2e-08 | 31–154 | Methyltransferase domain |
Methyltransf_31 | PF13847.13 | 3.1e-13 | 45–169 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 1.8e-15 | 46–144 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 4.0e-12 | 47–148 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 2.5e-10 | 47–145 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: eccD3 (ESX-3 secretion system protein EccD), medium confidence from genomic context alone (score 546 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) |
|---|---|---|---|---|
Rv3698 hyp |
hypothetical protein | 717 | 716 ctx | neighborhood:715 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 545 | 546 ctx | cooccurence:543 |
Rv3697c vapC48 |
ribonuclease VapC48 | 527 | 527 ctx | neighborhood:522 |
Rv3697A vapB48 |
antitoxin VapB48 | 520 | 520 ctx | neighborhood:520 |
Rv2751 hyp |
hypothetical protein | 503 | 504 ctx | cooccurence:499 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 447 | 447 ctx | cooccurence:447 |
Rv3696c glpK |
glycerol kinase | 444 | 443 ctx | neighborhood:435 |
Rv0256c PPE2 |
PPE family protein PPE2 | 420 | 420 ctx | cooccurence:415 |
Rv2687c |
antibiotic ABC transporter permease | 416 | 416 ctx | cooccurence:413 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 413 | 414 ctx | cooccurence:412 |
Rv3896c hyp |
hypothetical protein | 413 | 414 ctx | cooccurence:410 |
Rv2686c |
antibiotic ABC transporter permease | 410 | 410 ctx | cooccurence:407 |
Rv2633c hyp |
hypothetical protein | 404 | 404 | |
Rv3707c hyp |
hypothetical protein | 401 | 402 ctx | cooccurence:400 |
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): TPMT PF05724.18 (E=1e-13), Methyltransf_23 PF13489.13 (E=2e-08), Methyltransf_31 PF13847.13 (E=3e-13), Methyltransf_25 PF13649.13 (E=2e-15), Methyltransf_11 PF08241.19 (E=4e-12), Methyltransf_12 PF08242.19 (E=3e-10)
- (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_218216.1)
- Domains: Pfam-A via hmmscan --cut_ga — TPMT (PF05724.18), 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 O69667 (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 —
14 functional partner(s); context anchor
eccD3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003921|Rv3699| MTDEVMDWDSAYREQGAFEGPPPWNIGEPQPELATLIAAGKVRSDVLDAGCGYAELSLALAADGYTVVGIDLTPTAVAAATKAAEERGLTTASFVQADITEFAAYPAGSAGRFSTVIDSTLFHSLPVDSRDRYLSSVHRAAAPGASYYVLVFAKGAFPAELEVKPNEVDEDELRAAVSKYWKIDEIRPAFIHVNPVTIPPQLAGAPVEFPPYDHDEKGRVKFPAYLLTAHKAG