cobH Resolved · high auto-curated
H37Rv Rv2065 · MTBC0 mtbc0_002199 ·
208 aa · 2351165–2351791 (+) ·
RefSeq NP_216581.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | precorrin-8X methylmutase |
|---|---|
| MTBC0 PGAP re-annotation | precorrin-8X methylmutase |
| Revised (this work) | Precorrin-8X methylmutase. Pfam: CbiC (PF02570.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP87
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Precorrin-8X methylmutase |
| EC (curated) |
EC 5.4.99.61
|
| Curated function | Catalyzes the conversion of precorrin-8X to hydrogenobyrinate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobH |
| eggNOG description | Precorrin-8X methylmutase |
| Orthologous group | COG2082 |
| EC number |
EC 5.4.99.60, EC 5.4.99.61
|
| KEGG orthology |
K06042
|
| 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 | 0.092 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 13 synonymous, 2 missense, 1 nonsense, 3 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 0.59% of strains (852) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
CbiC | PF02570.21 | 4.9e-68 | 10–204 | Precorrin-8X methylmutase |
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 | neighborhood:881 fusion:897 cooccurence:774 coexpression:982 textmining:554 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 999 | 999 ctx | cooccurence:774 coexpression:972 database:900 textmining:578 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 997 | 994 ctx | fusion:547 cooccurence:767 coexpression:408 database:900 textmining:653 |
Rv2064 cobG |
precorrin-3B synthase | 998 | 992 ctx | neighborhood:876 fusion:806 cooccurence:665 textmining:818 |
Rv0255c cobQ1 |
cobyric acid synthase | 977 | 970 ctx | fusion:589 cooccurence:650 coexpression:778 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 979 | 959 ctx | cooccurence:772 coexpression:799 textmining:511 |
Rv2070c cobK |
precorrin-6A reductase | 986 | 949 ctx | cooccurence:774 coexpression:753 textmining:746 |
Rv2062c cobN |
cobalamin biosynthesis protein CobN | 935 | 897 ctx | neighborhood:633 cooccurence:696 textmining:400 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 900 | 870 ctx | cooccurence:732 coexpression:458 |
Rv2063A mazF7 |
mRNA interferase MazF7 | 867 | 867 ctx | neighborhood:867 |
Rv2063 mazE7 |
antitoxin MazE7 | 772 | 772 ctx | neighborhood:770 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 890 | 720 ctx | cooccurence:448 coexpression:446 textmining:626 |
Rv2423 hyp |
hypothetical protein | 727 | 691 | coexpression:673 |
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 881 | 673 ctx | cooccurence:427 textmining:654 |
Rv2849c cobO |
cob(I)alamin adenosyltransferase | 850 | 493 ctx | cooccurence:404 textmining:717 |
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-8X methylmutase
- MTBC0 PGAP product: precorrin-8X methylmutase
- Pfam (hmmscan --cut_ga): CbiC PF02570.21 (E=5e-68)
- (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_216581.1)
- Domains: Pfam-A via hmmscan --cut_ga — CbiC (PF02570.21)
- 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
COG2082 - Curated reference: UniProt P9WP87 (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 —
42 functional partner(s); context anchor
cobIJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002199|Rv2065|cobH MLDYLRDAAEIYRRSFAVIRAEADLARFPADVARVVVRLIHTCGQVDVAEHVAYTDDVVARAGAALAAGAPVLCDSSMVAAGITTSRLPADNQIVSLVADPRATELAARRQTTRSAAGVELCAERLPGAVLAIGNAPTALFRLLELVDEGAPPPAAVLGGPVGFVGSAQAKEELIERPRGMSYLVVRGRRGGSAMAAAAVNAIASDRE