cobIJ Resolved · high auto-curated
H37Rv Rv2066 · MTBC0 mtbc0_002200 ·
508 aa · 2351788–2353314 (+) ·
RefSeq NP_216582.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase |
|---|---|
| MTBC0 PGAP re-annotation | precorrin-2 C(20)-methyltransferase |
| Revised (this work) | Precorrin-2 C(20)-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 |
P9WGB3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cobalamin biosynthesis protein CobIJ [Includes: Precorrin-2 C(20)-methyltransferase |
| EC (curated) |
EC 2.1.1.130, EC 2.1.1.131
|
| Curated function | Methylates precorrin-2 at the C-20 position to produce precorrin-3A. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobIJ |
| eggNOG description | Belongs to the precorrin methyltransferase family |
| Orthologous group | COG1010 |
| EC number |
EC 2.1.1.130, EC 2.1.1.131
|
| KEGG orthology |
K05934, K13540
|
| KEGG pathways |
map00860, map01100
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.345 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 11 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 |
|---|---|---|---|---|
TP_methylase | PF00590.26 | 1.1e-41 | 6–219 | Tetrapyrrole (Corrin/Porphyrin) Methylases |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobM (precorrin-4 C(11)-methyltransferase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 999 | 1000 ctx | cooccurence:765 coexpression:999 database:900 textmining:554 |
Rv2065 cobH |
precorrin-8X methylmutase | 999 | 1000 ctx | neighborhood:881 fusion:897 cooccurence:774 coexpression:982 textmining:554 |
Rv2070c cobK |
precorrin-6A reductase | 999 | 1000 ctx | cooccurence:773 coexpression:999 textmining:554 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 999 | 1000 ctx | neighborhood:544 cooccurence:774 coexpression:997 textmining:850 |
Rv0255c cobQ1 |
cobyric acid synthase | 999 | 999 ctx | fusion:726 cooccurence:469 coexpression:990 textmining:596 |
Rv2064 cobG |
precorrin-3B synthase | 998 | 997 ctx | neighborhood:876 cooccurence:760 database:900 textmining:529 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 991 | 982 | coexpression:963 textmining:554 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 991 | 969 ctx | neighborhood:544 database:900 textmining:745 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 987 | 964 ctx | neighborhood:544 database:900 textmining:660 |
Rv2423 hyp |
hypothetical protein | 965 | 943 | coexpression:932 textmining:418 |
Rv2062c cobN |
cobalamin biosynthesis protein CobN | 969 | 926 ctx | neighborhood:672 cooccurence:759 textmining:608 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 959 | 912 ctx | cooccurence:755 coexpression:463 textmining:554 |
Rv2850c |
magnesium chelatase | 858 | 838 ctx | neighborhood:544 cooccurence:648 |
Rv2063A mazF7 |
mRNA interferase MazF7 | 792 | 792 ctx | neighborhood:792 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 940 | 786 ctx | cooccurence:647 textmining:734 |
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: bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase
- MTBC0 PGAP product: precorrin-2 C(20)-methyltransferase
- Pfam (hmmscan --cut_ga): TP_methylase PF00590.26 (E=1e-41)
- (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_216582.1)
- 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
COG1010 - Curated reference: UniProt P9WGB3 (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 —
67 functional partner(s); context anchor
cobM - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002200|Rv2066|cobIJ MSARGTLWGVGLGPGDPELVTVKAARVIGEADVVAYHSAPHGHSIARGIAEPYLRPGQLEEHLVYPVTTEATNHPGGYAGALEDFYADATERIATHLDAGRNVALLAEGDPLFYSSYMHLHTRLTRRFNAVIVPGVTSVSAASAAVATPLVAGDQVLSVLPGTLPVGELTRRLADADAAVVVKLGRSYHNVREALSASGLLGDAFYVERASTAGQRVLPAADVDETSVPYFSLAMLPGGRRRALLTGTVAVVGLGPGDSDWMTPQSRRELAAATDLIGYRGYLDRVEVRDGQRRHPSDNTDEPARARLACSLADQGRAVAVVSSGDPGVFAMATAVLEEAEQWPGVRVRVIPAMTAAQAVASRVGAPLGHDYAVISLSDRLKPWDVIAARLTAAAAADLVLAIYNPASVTRTWQVGAMRELLLAHRDPGIPVVIGRNVSGPVSGPNEDVRVVKLADLNPAEIDMRCLLIVGSSQTRWYSVDSQDRVFTPRRYPEAGRATATKSSRHSD