Rv2172c Resolved · high auto-curated
H37Rv Rv2172c · MTBC0 mtbc0_002306 ·
301 aa · 2459638–2460543 (-) ·
RefSeq NP_216688.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | mycobacterial-type methylenetetrahydrofolate reductase |
| Revised (this work) | Mycobacterial-type methylenetetrahydrofolate reductase. Pfam: MTHFR_2 (PF19345.6). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53506
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| eggNOG description | methylenetetrahydrofolate reductase (NAD(P)H) activity |
| Orthologous group | COG0685 |
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 | 0.673 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 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 |
|---|---|---|---|---|
MTHFR_2 | PF19345.6 | 8.7e-157 | 2–295 | Mycobacterial methylenetetrahydrofolate reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: idsA2 (geranylgeranyl pyrophosphate synthetase IdsA), high confidence from genomic context alone (score 736 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) |
|---|---|---|---|---|
Rv2124c metH |
methionine synthase | 990 | 977 | coexpression:964 textmining:583 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 855 | 767 | coexpression:726 textmining:405 |
Rv3015c hyp |
hypothetical protein | 841 | 765 | coexpression:723 |
Rv2173 idsA2 |
geranylgeranyl pyrophosphate synthetase IdsA | 749 | 736 ctx | neighborhood:706 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 762 | 730 | coexpression:677 |
Rv1079 metB |
cystathionine gamma-synthase | 760 | 728 | coexpression:675 |
Rv1392 metK |
S-adenosylmethionine synthetase | 774 | 705 | coexpression:681 |
Rv3793 embC |
arabinosyltransferase C | 634 | 634 ctx | cooccurence:634 |
Rv0817c lmeA hyp |
hypothetical protein | 620 | 620 ctx | cooccurence:620 |
Rv3859c gltB |
glutamate synthase large subunit | 667 | 616 ctx | neighborhood:544 |
Rv1610 |
membrane protein | 579 | 579 ctx | cooccurence:577 |
Rv3795 embB |
arabinosyltransferase B | 576 | 576 ctx | cooccurence:575 |
Rv3707c hyp |
hypothetical protein | 572 | 572 ctx | cooccurence:572 |
Rv0431 |
tuberculin-like peptide | 567 | 568 ctx | cooccurence:565 |
Rv2360c hyp |
hypothetical protein | 563 | 563 ctx | cooccurence:562 |
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: mycobacterial-type methylenetetrahydrofolate reductase
- Pfam (hmmscan --cut_ga): MTHFR_2 PF19345.6 (E=9e-157)
- (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_216688.1)
- Domains: Pfam-A via hmmscan --cut_ga — MTHFR_2 (PF19345.6)
- 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
COG0685 - Curated reference: UniProt O53506 (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 —
57 functional partner(s); context anchor
idsA2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002306|Rv2172c| MTLNTIALELVPPNLEGGKERAIEDARKVVQYSAASGLDGRIRHVMMPGMIAEDDDRPIPMQPKLDVLDFWSIIKPELAGVHGLCTQVTAFMDEPSLHRRLVDLSDAGMEGIVFVGVPRTMQDGEGSGVAPTDALSLYRQLVANRGVIVIPTRDGEQGRLNFKCSRGATYGMTQLLYSDAIVGFLREFARTTEHRPEILLSFGFVPKVETRIGLINWLIQDPGNAAVADEQAFVQKLAGSEPARRRRLMVDLYKRVLDGVADLGFPLSIHLEATYGVSAAAFETFAEMLAYWSPAEPGKPD