cobQ1 Resolved · high auto-curated
H37Rv Rv0255c · MTBC0 - ·
494 aa · 306374–307858 (-) ·
RefSeq YP_177703.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cobyric acid synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Cobyric acid synthase. Pfam: AAA_26 (PF13500.13), CbiA (PF01656.30), GATase_3 (PF07685.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WP95
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cobyric acid synthase |
| Curated function | Catalyzes amidations at positions B, D, E, and G on adenosylcobyrinic A,C-diamide. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobQ |
| eggNOG description | Catalyzes amidations at positions B, D, E, and G on adenosylcobyrinic A,C-diamide. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation |
| Orthologous group | COG1492 |
| EC number |
EC 6.3.5.10
|
| KEGG orthology |
K02232
|
| KEGG pathways |
map00860, map01100
|
| KEGG modules |
M00122
|
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 | 0.479 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 9 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.36% of strains (519) · 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 |
|---|---|---|---|---|
AAA_26 | PF13500.13 | 9.3e-15 | 3–233 | AAA domain |
CbiA | PF01656.30 | 3.7e-24 | 5–234 | CobQ/CobB/MinD/ParA nucleotide binding domain |
GATase_3 | PF07685.21 | 1.8e-43 | 255–429 | CobB/CobQ-like glutamine amidotransferase domain |
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 999 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 | 999 ctx | fusion:726 cooccurence:469 coexpression:990 textmining:596 |
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 998 | 989 ctx | neighborhood:757 fusion:640 cooccurence:769 coexpression:525 textmining:845 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 994 | 981 ctx | cooccurence:774 database:900 textmining:734 |
Rv2849c cobO |
cob(I)alamin adenosyltransferase | 989 | 971 ctx | cooccurence:674 database:900 textmining:648 |
Rv2065 cobH |
precorrin-8X methylmutase | 977 | 970 ctx | fusion:589 cooccurence:650 coexpression:778 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 968 | 958 ctx | fusion:667 cooccurence:766 coexpression:426 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 957 | 944 ctx | cooccurence:724 coexpression:774 |
Rv2231c cobC |
aminotransferase | 952 | 944 ctx | fusion:899 |
Rv1314c |
cob(I)yrinic acid a,c-diamide adenosyltransferase | 918 | 910 | database:900 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 946 | 900 ctx | cooccurence:772 coexpression:508 textmining:485 |
Rv2070c cobK |
precorrin-6A reductase | 912 | 885 | coexpression:799 |
Rv2207 cobT |
nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase | 906 | 878 ctx | cooccurence:767 coexpression:426 |
Rv0256c PPE2 |
PPE family protein PPE2 | 915 | 765 ctx | neighborhood:759 textmining:656 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 885 | 754 | coexpression:513 textmining:553 |
Rv2861c mapB |
methionine aminopeptidase | 544 | 544 ctx | neighborhood:544 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): cobyric acid synthase
- Pfam (hmmscan --cut_ga): AAA_26 PF13500.13 (E=9e-15), CbiA PF01656.30 (E=4e-24), GATase_3 PF07685.21 (E=2e-43)
- (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 YP_177703.1)
- Domains: Pfam-A via hmmscan --cut_ga — AAA_26 (PF13500.13), CbiA (PF01656.30), GATase_3 (PF07685.21)
- 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
COG1492 - Curated reference: UniProt P9WP95 (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 —
48 functional partner(s); context anchor
cobIJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0255c|cobQ1 MSGLLVAGTTSDAGKSAVTAGLCRALARRGVRVAPFKAQNMSNNSMVCRGPDGTGVEIGRAQWVQALAARTTPEAAMNPVLLKPASDHRSHVVLMGKPWGEVASSSWCAGRRALAEAACRAFDALAARYDVVVAEGAGSPAEINLRAGDYVNMGLARHAGLPTIVVGDIDRGGVFAAFLGTVALLAAEDQALVAGFVVNKFRGDSDLLAPGLRDLERVTGRRVYGTLPWHPDLWLDSEDALDLQGRRAAGTGARRVAVVRLPRISNFTDVDALGLEPDLDVVFASDPRALDDADLIVLPGTRATIADLAWLRARDLDRALLVHVAAGKPLLGICGGFQMLGRVIRDPYGIEGPGGQVTEVEGLGLLDVETAFSPHKVLRLPRGEGLGVPASGYEIHHGRITRGDTAEEFLGGARDGPVFGTMWHGSLEGDALREAFLRETLGLAPSGSCFLAARERRLDLLGDLVERHLDVDALLNLARHGCPPTLPFLAPGAP