cobK Resolved · high auto-curated
H37Rv Rv2070c · MTBC0 mtbc0_002204 ·
244 aa · 2356104–2356838 (-) ·
RefSeq NP_216586.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | precorrin-6A reductase |
|---|---|
| MTBC0 PGAP re-annotation | cobalt-precorrin-6A reductase |
| Revised (this work) | Cobalt-precorrin-6A reductase. Pfam: CbiJ (PF02571.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP89
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Precorrin-6A reductase |
| EC (curated) |
EC 1.3.1.54
|
| Curated function | Catalyzes the reduction of the macrocycle of precorrin-6X into precorrin-6Y. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobK |
| eggNOG description | reductase |
| Orthologous group | COG2099 |
| EC number |
EC 1.3.1.106, EC 1.3.1.54
|
| KEGG orthology |
K05895
|
| 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) pseudogene candidate
| pN/pS | 0.767 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 17.66% of strains (25647) · 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 |
|---|---|---|---|---|
CbiJ | PF02571.21 | 1.1e-73 | 3–238 | Precorrin-6x reductase CbiJ/CobK |
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:773 coexpression:999 textmining:554 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 999 | 999 ctx | neighborhood:881 cooccurence:774 coexpression:665 database:900 textmining:850 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 998 | 994 ctx | neighborhood:881 cooccurence:740 coexpression:818 textmining:753 |
Rv2065 cobH |
precorrin-8X methylmutase | 986 | 949 ctx | cooccurence:774 coexpression:753 textmining:746 |
Rv0255c cobQ1 |
cobyric acid synthase | 912 | 885 | coexpression:799 |
Rv2073c |
oxidoreductase | 805 | 805 ctx | neighborhood:796 |
Rv2074 |
pyridoxamine 5'-phosphate oxidase | 764 | 764 ctx | neighborhood:731 |
Rv2064 cobG |
precorrin-3B synthase | 910 | 759 ctx | cooccurence:744 textmining:644 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 898 | 758 ctx | cooccurence:664 textmining:598 |
Rv2062c cobN |
cobalamin biosynthesis protein CobN | 960 | 749 ctx | cooccurence:704 textmining:851 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 789 | 725 | coexpression:654 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 743 | 664 ctx | cooccurence:526 |
Rv2850c |
magnesium chelatase | 484 | 484 | |
Rv2423 hyp |
hypothetical protein | 525 | 462 | coexpression:431 |
Rv1487 hyp |
hypothetical protein | 441 | 441 | coexpression:423 |
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-6A reductase
- MTBC0 PGAP product: cobalt-precorrin-6A reductase
- Pfam (hmmscan --cut_ga): CbiJ PF02571.21 (E=1e-73)
- (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_216586.1)
- Domains: Pfam-A via hmmscan --cut_ga — CbiJ (PF02571.21)
- 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
COG2099 - Curated reference: UniProt P9WP89 (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 —
33 functional partner(s); context anchor
cobIJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002204|Rv2070c|cobK MTRVLLLGGTAEGRALAKELHPHVEIVSSLAGRVPNPALPIGPVRIGGFGGVEGLRGWLREERIDAVVDATHPFAVTITAHAAQVCGELGLPYLVLARPPWDPGTAIIAVSDIEAADVVAEQGYSRVFLTTGRSGIAAFANSDAWFLIRVVTAPDGTALPRRHKLVLSRGPYGYHDEFALLREQRIDALVTKNSGGKMTRAKLDAAAALGISVVMIARPLLPAGVAAVDSVHRAAMWVAGLPSR