Rv3528c Family assigned · low auto-curated · to review
H37Rv Rv3528c · MTBC0 mtbc0_003744 ·
237 aa · 3988156–3988869 (-) ·
RefSeq NP_218045.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 7pga-assembly2_D Chimeric carminomycin-4-O-methyltransferase (DnrK) with regions (prob 1.00, TM 0.55). Structure-based, putative. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Curated reference (UniProt)
| UniProt |
I6YGE4
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Methyltransferase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 290BN |
|---|
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 | 0.507 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 5 missense, 2 nonsense, 2 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 0.32% of strains (467) · convergent |
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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 95.5 (very high). 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 |
|---|---|---|---|---|
7pga-assembly2_D |
1.00 | 0.55 | 1.0e-09 sig | 7pga-assembly2_D Chimeric carminomycin-4-O-methyltransferase (DnrK) with regions from 10-hydroxylase RdmB and 10-decarboxylase TamK |
7d8d-assembly1_A |
1.00 | 0.58 | 2.2e-08 sig | 7d8d-assembly1_A The crystal structure of ScNTM1 in complex with SAH and Rps25a hexapeptide |
5ufm-assembly1_A |
1.00 | 0.59 | 1.8e-08 sig | 5ufm-assembly1_A Crystal structure of Burkholderia thailandensis 1,6-didemethyltoxoflavin-N1-methyltransferase with bound 1,6-didemethyltoxoflavin and S-adenosylhomocysteine |
5jr3-assembly1_A |
1.00 | 0.55 | 5.1e-09 sig | 5jr3-assembly1_A Crystal structure of carminomycin-4-O-methyltransferase DnrK in complex with SAH and 4-methylumbelliferone |
7pga-assembly1_A |
1.00 | 0.49 | 3.1e-09 sig | 7pga-assembly1_A Chimeric carminomycin-4-O-methyltransferase (DnrK) with regions from 10-hydroxylase RdmB and 10-decarboxylase TamK |
5eeg-assembly1_A |
1.00 | 0.54 | 4.5e-08 sig | 5eeg-assembly1_A Crystal structure of carminomycin-4-O-methyltransferase DnrK in complex with tetrazole-SAH |
9j56-assembly1_A |
1.00 | 0.55 | 4.2e-08 sig | 9j56-assembly1_A Functional Investigation of the SAM-Dependent Methyltransferases Rdmb in Anthracycline Biosynthesis |
9fcs-assembly2_B |
1.00 | 0.62 | 1.9e-07 sig | 9fcs-assembly2_B CysG(N-16)-H122N mutant in complex with SAH from Kitasatospora cystarginea |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3779 |
transmembrane protein | 553 | 50 | textmining:549 |
Rv0495c hyp |
hypothetical protein | 440 | 50 | textmining:435 |
Rv3527 hyp |
hypothetical protein | 441 | 47 | textmining:438 |
Rv1084 hyp |
hypothetical protein | 803 | 41 | textmining:803 |
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: hypothetical protein
- Foldseek best: 7pga-assembly2_D Chimeric carminomycin-4-O-methyltransferase (DnrK) with regions (prob 1.00, E=1e-09, TM=0.55)
- (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_218045.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
290BN - Curated reference: UniProt I6YGE4 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 95.5, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 4 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003744|Rv3528c| MMLDRLRQGGYWLVRGKINLIDRAFTSCRIESFADLGAVWGVEGAYTFRALDKYPVKEAVLVDGRITPTVAARANSYPQLRVIEGNFGDQEIADKVGNVDALFLFDVLLHQVSPDWDTILDMYAKNVRCLLIYNQQWIGSTTTVRLLDLGEKHYFRNVPHSKLNKAYRDLFQKLDKKHPDHDKPWRDIPDIWQWGITDADLESKASELGFKLLYKEDCRGFGWLPNIQNRAFLFARQ