Rv3015c Resolved · high auto-curated
H37Rv Rv3015c · MTBC0 mtbc0_003204 ·
337 aa · 3395960–3396973 (-) ·
RefSeq NP_217531.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | methionine synthase |
| Revised (this work) | Methionine synthase. Pfam: Meth_synt_2 (PF01717.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YAW3
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cobalamin-independent methionine synthase MetE C-terminal/archaeal domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| eggNOG description | Methionine synthase |
| Orthologous group | COG0620 |
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 | 0.658 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
Meth_synt_2 | PF01717.25 | 8.5e-82 | 4–328 | Cobalamin-independent synthase, Catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lpqA (lipoprotein LpqA), high confidence from genomic context alone (score 783 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) |
|---|---|---|---|---|
Rv3016 lpqA |
lipoprotein LpqA | 782 | 783 ctx | neighborhood:782 |
Rv2172c hyp |
hypothetical protein | 841 | 765 | coexpression:723 |
Rv3014c ligA |
DNA ligase A | 748 | 748 ctx | neighborhood:740 |
Rv1392 metK |
S-adenosylmethionine synthetase | 736 | 701 | coexpression:644 |
Rv1433 ldtMt3 hyp |
hypothetical protein | 659 | 659 ctx | cooccurence:658 |
Rv0192 hyp |
hypothetical protein | 635 | 635 ctx | cooccurence:635 |
Rv0116c ldtA |
L,D-transpeptidase LdtA | 627 | 627 ctx | cooccurence:627 |
Rv2867c |
GCN5-like N-acetyltransferase | 624 | 624 ctx | cooccurence:624 |
Rv2239c hyp |
hypothetical protein | 614 | 614 ctx | cooccurence:614 |
Rv2518c ldtB |
L,D-transpeptidase LdtB | 611 | 611 ctx | cooccurence:609 |
Rv0483 lprQ |
lipoprotein LprQ | 590 | 575 ctx | cooccurence:575 |
Rv2124c metH |
methionine synthase | 875 | 574 | coexpression:516 textmining:720 |
Rv3268 hyp |
hypothetical protein | 574 | 574 ctx | cooccurence:569 |
Rv3256c hyp |
hypothetical protein | 573 | 557 ctx | cooccurence:556 |
Rv3248c sahH |
adenosylhomocysteinase | 586 | 531 | coexpression:504 |
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: methionine synthase
- Pfam (hmmscan --cut_ga): Meth_synt_2 PF01717.25 (E=8e-82)
- (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_217531.1)
- Domains: Pfam-A via hmmscan --cut_ga — Meth_synt_2 (PF01717.25)
- 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
COG0620 - Curated reference: UniProt I6YAW3 (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 —
51 functional partner(s); context anchor
lpqA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003204|Rv3015c| MSVFATATGIGSWPGTAAREAAQVVVGELAGALAYLTELPARGVGADMLGRAGGLLVDVAIDTVPRGYRIAARPGAVTRRAASLLDEDMDALEEAWETAGLRGCGRAVKVQAPGPVTLVAGLELANGHRAITDPGAVRDLAASLAEGVAAHRAALARRLDTPVVVQFDEPSLPAALGGRLTGVTALSPVAPLDETVAEALLDTCIAAVDADVALHSCSPDLPWDLLQRSRISAVSVDASTLQAADLDAVAAFVESGRTVVLGLVPVTAPERAPSMEEVAAAAVAVTDRLGVPRSALRDRLGVSPACGLANATGQWARTAVGLARDVAEAFARDPEAI