cobM Resolved · high auto-curated
H37Rv Rv2071c · MTBC0 mtbc0_002205 ·
251 aa · 2356835–2357590 (-) ·
RefSeq NP_216587.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | precorrin-4 C(11)-methyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | precorrin-4 C(11)-methyltransferase |
| Revised (this work) | Precorrin-4 C(11)-methyltransferase. Pfam: TP_methylase (PF00590.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGB1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Precorrin-4 C(11)-methyltransferase |
| EC (curated) |
EC 2.1.1.133
|
| Curated function | Catalyzes the methylation of C-11 in precorrin-4 to form precorrin-5. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobM |
| eggNOG description | Belongs to the precorrin methyltransferase family |
| Orthologous group | COG2875 |
| EC number |
EC 2.1.1.133, EC 2.1.1.271
|
| KEGG orthology |
K05936
|
| KEGG pathways |
map00860, map01100
|
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 | 0.232 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (243) · 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 |
|---|---|---|---|---|
TP_methylase | PF00590.26 | 5.5e-47 | 2–209 | Tetrapyrrole (Corrin/Porphyrin) Methylases |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobIJ (bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase | 999 | 1000 ctx | cooccurence:765 coexpression:999 database:900 textmining:554 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 999 | 998 ctx | neighborhood:881 cooccurence:735 coexpression:924 textmining:888 |
Rv2070c cobK |
precorrin-6A reductase | 998 | 994 ctx | neighborhood:881 cooccurence:740 coexpression:818 textmining:753 |
Rv2065 cobH |
precorrin-8X methylmutase | 979 | 959 ctx | cooccurence:772 coexpression:799 textmining:511 |
Rv0255c cobQ1 |
cobyric acid synthase | 957 | 944 ctx | cooccurence:724 coexpression:774 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 940 | 879 ctx | cooccurence:771 coexpression:406 textmining:533 |
Rv2073c |
oxidoreductase | 805 | 805 ctx | neighborhood:796 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 835 | 785 ctx | cooccurence:749 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 819 | 764 ctx | cooccurence:563 coexpression:410 |
Rv2074 |
pyridoxamine 5'-phosphate oxidase | 732 | 732 ctx | neighborhood:731 |
Rv0510 hemC |
porphobilinogen deaminase | 749 | 714 ctx | fusion:414 cooccurence:492 |
Rv2423 hyp |
hypothetical protein | 721 | 684 | coexpression:666 |
Rv2207 cobT |
nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase | 747 | 669 ctx | cooccurence:568 |
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 954 | 634 ctx | cooccurence:461 textmining:880 |
Rv0512 hemB |
delta-aminolevulinic acid dehydratase | 622 | 569 ctx | cooccurence:532 |
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: precorrin-4 C(11)-methyltransferase
- MTBC0 PGAP product: precorrin-4 C(11)-methyltransferase
- Pfam (hmmscan --cut_ga): TP_methylase PF00590.26 (E=6e-47)
- (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_216587.1)
- Domains: Pfam-A via hmmscan --cut_ga — TP_methylase (PF00590.26)
- 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
COG2875 - Curated reference: UniProt P9WGB1 (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 —
35 functional partner(s); context anchor
cobIJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002205|Rv2071c|cobM MTVYFIGAGPGAADLITVRGQRLLQRCPVCLYAGSIMPDDLLAQCPPGATIVDTGPLTLEQIVRKLADADADGRDVARLHSGDPSLYSALAEQCRELDALGIGYEIVPGVPAFAAAAAALKRELTVPGVAQTVTLTRVATLSTPMPPGEDLAALARSRATLVLHLAAAQIDAIVPRLLDGGYRPETPVAVVAFASWPQQRTLRGTLADIAARMHDAKITRTAVIVVGDVLTAEGFTDSYLYSVARHGRYAQ