Rv2067c Resolved · high auto-curated
H37Rv Rv2067c · MTBC0 mtbc0_002201 ·
407 aa · 2353260–2354483 (-) ·
RefSeq NP_216583.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | class I SAM-dependent methyltransferase |
| Revised (this work) | Class I SAM-dependent methyltransferase. Pfam: Methyltransf_9 (PF08003.18), Methyltransf_25 (PF13649.13), Methyltransf_31 (PF13847.13), Methyltransf_12 (PF08242.19), Methyltransf_11 (PF08241.19), Methyltransf_23 (PF13489.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WLL9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | S-adenosyl-L-methionine-dependent methyltransferase Rv2067c |
| EC (curated) |
EC 2.1.1.360
|
| Curated function | Involved in epigenetic reprogramming of the human host cells for the benefit of intracellular survival of the pathogen. Trimethylates 'Lys-79' of human histone H3 forming the so called H3K79me3 mark in the THP-1 macrophages upon M.tuberculosis infection. Acts specifically on free non-nucleosomal histone H3. Alters gene expression of the macrophage post-infection by adding the H3K79me3 mark on genes involved in defense response to increase pathogenesis. Represses methyltransferase DOT1L resulting in reduction of DOT1L-specific nucleosomal H3K79me3 mark and thus in reduced expression of pro-infl. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Methyltransferase domain |
| Orthologous group | COG0500 |
| Gene Ontology (20) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0008150, GO:0008152, GO:0008168, GO:0008757 +8 more
|
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 | 0.368 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 7 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.22% of strains (321) · clonal |
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 |
|---|---|---|---|---|
Methyltransf_9 | PF08003.18 | 1.4e-05 | 58–155 | Protein of unknown function (DUF1698) |
Methyltransf_25 | PF13649.13 | 2.2e-12 | 59–153 | Methyltransferase domain |
Methyltransf_31 | PF13847.13 | 3.7e-12 | 59–156 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 9.0e-16 | 62–155 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 1.5e-13 | 62–156 | Methyltransferase domain |
Methyltransf_23 | PF13489.13 | 1.8e-07 | 62–157 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: blaC (beta-lactamase), high confidence from genomic context alone (score 777 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) |
|---|---|---|---|---|
Rv2068c blaC |
beta-lactamase | 778 | 777 ctx | neighborhood:772 |
Rv2423 hyp |
hypothetical protein | 776 | 777 ctx | cooccurence:773 |
Rv3899c hyp |
hypothetical protein | 748 | 748 ctx | cooccurence:748 |
Rv3435c |
transmembrane protein | 740 | 741 ctx | cooccurence:737 |
Rv3887c eccD2 |
ESX-2 secretion system protein EccD | 708 | 709 ctx | cooccurence:707 |
Rv2079 hyp |
hypothetical protein | 678 | 678 ctx | cooccurence:676 |
Rv1359 |
transcriptional regulator | 668 | 669 ctx | cooccurence:667 |
Rv3166c hyp |
hypothetical protein | 668 | 668 ctx | cooccurence:667 |
Rv0048c |
membrane protein | 668 | 668 ctx | cooccurence:668 |
Rv1795 eccD5 |
ESX-5 type VII secretion system protein EccD | 624 | 624 ctx | cooccurence:622 |
Rv2939 papA5 |
phthiocerol/phthiodiolone dimycocerosyl transferase | 607 | 607 ctx | cooccurence:603 |
Rv3843c |
transmembrane protein | 598 | 598 ctx | cooccurence:597 |
Rv2387 hyp |
hypothetical protein | 567 | 567 ctx | cooccurence:565 |
Rv1816 |
HTH-type transcriptional regulator | 565 | 566 ctx | cooccurence:560 |
Rv0977 PE_PGRS16 |
PE-PGRS family protein PE_PGRS16 | 563 | 563 ctx | cooccurence:563 |
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: class I SAM-dependent methyltransferase
- Pfam (hmmscan --cut_ga): Methyltransf_9 PF08003.18 (E=1e-05), Methyltransf_25 PF13649.13 (E=2e-12), Methyltransf_31 PF13847.13 (E=4e-12), Methyltransf_12 PF08242.19 (E=9e-16), Methyltransf_11 PF08241.19 (E=1e-13), Methyltransf_23 PF13489.13 (E=2e-07)
- (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_216583.1)
- Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_9 (PF08003.18), Methyltransf_25 (PF13649.13), Methyltransf_31 (PF13847.13), Methyltransf_12 (PF08242.19), Methyltransf_11 (PF08241.19), Methyltransf_23 (PF13489.13)
- 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
COG0500 - Curated reference: UniProt P9WLL9 (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 —
46 functional partner(s); context anchor
blaC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002201|Rv2067c| MTDDHPRADIVSRQYHRWLYPHPIADLEAWTTANWEWFDPVHSHRILWPDREYRPDLDILIAGCGTNQAAIFAFTNRAAKVVAIDISRPALDHQQYLKDKHGLANLELHLLPIEELATLGRDFDLVVSTGVLHHLADPRAGMKELAHCLRRDGVVAAMLYGKYGRIGVELLGSVFRDLGLGQDDASIKLAKEAISLLPTYHPLRNYLTKARDLLSDSALVDTFLHGRQRSYTVEECVDLVTSAGLVFQGWFHKAPYYPHDFFVPNSEFYAAVNTLPEVKAWSVMERLETLNATHLFMACRRDRPKEQYTIDFSTVAALDYVPLMRTRCGVSGTDMFWPGWRMAPSPAQLAFLQQVDGRRTIREIAGCVARTGEPSGGSLADLEEFGRKLFQSLWRLDFVAVALPASG