Rv2239c Family assigned · medium
H37Rv Rv2239c · MTBC0 - ·
158 aa · 2511176–2511652 (-) ·
RefSeq NP_216755.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | S-adenosyl-methionine (SAM)-dependent methyltransferase fold. RefSeq leaves it 'hypothetical protein' (Pfam DUF3052). The AlphaFold model superposes on an O-methyltransferase bound to the product SAH (PDB 8bif; Foldseek prob 1.0, E 2e-5, TM 0.55). STRING context: peroxiredoxin ahpE (Rv2238c). A SAM-MTase fold assignment; the acceptor substrate is not determined. |
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 |
P9WLG9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2239c |
UniProt still lists this protein as Uncharacterized protein Rv2239c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF3052) |
| Orthologous group | 2B57P |
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 | 0.31 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 |
|---|---|---|---|---|
DUF3052 | PF11253.14 | 1.4e-55 | 29–152 | Protein of unknown function (DUF3052) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 81.5 (confident). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
7ux6-assembly1_A |
1.00 | 0.52 | 1.2e-04 sig | 7ux6-assembly1_A Crystal structure of MfnG, an L- and D-tyrosine O-methyltransferase from the marformycin biosynthesis pathway of Streptomyces drozdowiczii, with SAH bound at 1.35 A resolution (P212121 - form I) |
7ux6-assembly1_B |
1.00 | 0.53 | 3.5e-04 sig | 7ux6-assembly1_B Crystal structure of MfnG, an L- and D-tyrosine O-methyltransferase from the marformycin biosynthesis pathway of Streptomyces drozdowiczii, with SAH bound at 1.35 A resolution (P212121 - form I) |
5gm2-assembly2_K |
1.00 | 0.51 | 5.4e-04 sig | 5gm2-assembly2_K Crystal structure of methyltransferase TleD complexed with SAH and teleocidin A1 |
5gm2-assembly3_O |
1.00 | 0.47 | 3.7e-04 sig | 5gm2-assembly3_O Crystal structure of methyltransferase TleD complexed with SAH and teleocidin A1 |
3e8s-assembly1_A-2 |
1.00 | 0.48 | 5.4e-04 sig | 3e8s-assembly1_A-2 Crystal structure of Putative SAM Dependent Methyltransferase in Complex with SAH (NP_744700.1) from PSEUDOMONAS PUTIDA KT2440 at 2.10 A resolution |
5gm2-assembly2_L |
1.00 | 0.47 | 7.0e-04 sig | 5gm2-assembly2_L Crystal structure of methyltransferase TleD complexed with SAH and teleocidin A1 |
5gm2-assembly3_N |
1.00 | 0.47 | 4.5e-04 sig | 5gm2-assembly3_N Crystal structure of methyltransferase TleD complexed with SAH and teleocidin A1 |
3vc2-assembly11_K |
1.00 | 0.48 | 9.1e-04 sig | 3vc2-assembly11_K Crystal structure of geranyl diphosphate C-methyltransferase from Streptomyces coelicolor A3(2) in complex with Mg2+, geranyl diphosphate, and S-adenosyl-L-homocysteine |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ahpE (peroxiredoxin), high confidence from genomic context alone (score 912 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) |
|---|---|---|---|---|
Rv2238c ahpE |
peroxiredoxin | 972 | 912 ctx | neighborhood:882 textmining:699 |
Rv2240c hyp |
hypothetical protein | 977 | 831 ctx | neighborhood:829 textmining:870 |
Rv2699c hyp |
hypothetical protein | 751 | 752 ctx | cooccurence:751 |
Rv2882c frr |
ribosome recycling factor | 734 | 734 | coexpression:734 |
Rv1626 pdtaR |
two-component system transcriptional regulator | 732 | 732 | coexpression:732 |
Rv1630 rpsA |
30S ribosomal protein S1 | 731 | 731 | coexpression:731 |
Rv2867c |
GCN5-like N-acetyltransferase | 717 | 718 ctx | cooccurence:716 |
Rv2050 rbpA |
RNA polymerase-binding protein RbpA | 713 | 714 ctx | cooccurence:712 |
Rv2112c dop |
pup deamidase/depupylase | 663 | 664 ctx | cooccurence:659 |
Rv2708c hyp |
hypothetical protein | 661 | 661 ctx | cooccurence:658 |
Rv1460 sufR |
transcriptional regulator | 659 | 660 ctx | cooccurence:659 |
Rv3676 crp |
cAMP receptor protein | 650 | 650 ctx | cooccurence:645 |
Rv2572c aspS |
aspartate--tRNA ligase | 634 | 634 ctx | cooccurence:632 |
Rv2989 |
transcriptional regulator | 614 | 615 ctx | cooccurence:613 |
Rv3015c hyp |
hypothetical protein | 614 | 614 ctx | cooccurence:614 |
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
- Foldseek -> O-methyltransferase + SAH (8bif), prob 1.0, E 2e-5
- Pfam DUF3052
- STRING anchor ahpE/Rv2238c
- Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.
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_216755.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3052 (PF11253.14)
- 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
2B57P - Curated reference: UniProt P9WLG9 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 81.5, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
44 functional partner(s); context anchor
ahpE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2239c| MPIATVCTWPAETEGGSTVVAADHASNYARKLGIQRDQLIQEWGWDEDTDDDIRAAIEEACGGELLDEDTDEVIDVVLLWWRDGDGDLVDTLMDAIGPLAEDGVIWVVTPKTGQPGHVLPAEIAEAAPTAGLMPTSSVNLGNWSASRLVQPKSRAGKR