Rv3399 Resolved · high auto-curated
H37Rv Rv3399 · MTBC0 - ·
348 aa · 3816129–3817175 (+) ·
RefSeq NP_217916.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | S-adenosylmethionine-dependent methyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | S-adenosylmethionine-dependent methyltransferase. Pfam: LCM (PF04072.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WFH1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative S-adenosyl-L-methionine-dependent methyltransferase Rv3399 |
| EC (curated) |
EC 2.1.1.-
|
| Curated function | Exhibits S-adenosyl-L-methionine-dependent methyltransferase activity. |
UniProt still lists this protein as Putative S-adenosyl-L-methionine-dependent methyltransferase Rv3399; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| eggNOG description | Exhibits S-adenosyl-L-methionine-dependent methyltransferase activity |
| Orthologous group | COG3315 |
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 | 0.65 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 8 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 |
|---|---|---|---|---|
LCM | PF04072.21 | 2.9e-70 | 61–244 | Leucine carboxyl methyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: phyA (phytoene synthase), high confidence from genomic context alone (score 880 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3397c phyA |
phytoene synthase | 880 | 880 ctx | neighborhood:508 coexpression:767 |
Rv3398c idsA1 |
multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase | 789 | 789 ctx | neighborhood:567 coexpression:458 |
Rv3400 |
hydrolase | 638 | 638 ctx | neighborhood:633 |
Rv3401 |
glycosyl hydrolase | 620 | 621 ctx | neighborhood:609 |
Rv3396c guaA |
GMP synthase | 507 | 507 ctx | neighborhood:502 |
Rv0401 |
transmembrane protein | 461 | 462 ctx | neighborhood:462 |
Rv0400c fadE7 |
acyl-CoA dehydrogenase FadE7 | 426 | 426 ctx | neighborhood:423 |
Rv2794c pptT |
4'-phosphopantetheinyl transferase | 400 | 401 | |
Rv0155 pntAa |
NAD(P) transhydrogenase subunit alpha PntAa | 415 | 49 | textmining:411 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): S-adenosylmethionine-dependent methyltransferase
- Pfam (hmmscan --cut_ga): LCM PF04072.21 (E=3e-70)
- (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_217916.1)
- Domains: Pfam-A via hmmscan --cut_ga — LCM (PF04072.21)
- 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
COG3315 - Curated reference: UniProt P9WFH1 (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 —
9 functional partner(s); context anchor
phyA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3399| MARPMGKLPSNTRKCAQCAMAEALLEIAGQTINQKDLGRSGRMTRTDNDTWDLASSVGATATMIATARALASRAENPLINDPFAEPLVRAVGIDLFTRLASGELRLEDIGDHATGGRWMIDNIAIRTKFYDDFFGDATTAGIRQVVILAAGLDTRAYRLPWPPGTVVYEIDQPAVIKFKTRALANLNAEPNAERHAVAVDLRNDWPTALKNAGFDPARPTAFSAEGLLSYLPPQGQDRLLDAITALSAPDSRLATQSPLVLDLAEEDEKKMRMKSAAEAWRERGFDLDLTELIYFDQRNDVADYLAGSGWQVTTSTGKELFAAQGLPPFADDHITRFADRRYISAVLK