cobB Resolved · high auto-curated
H37Rv Rv2848c · MTBC0 mtbc0_003027 ·
457 aa · 3176814–3178187 (-) ·
RefSeq NP_217364.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cobyrinic acid A,C-diamide synthase |
|---|---|
| MTBC0 PGAP re-annotation | cobyrinate a%2Cc-diamide synthase |
| Revised (this work) | Cobyrinate a%2Cc-diamide synthase. Pfam: CbiA (PF01656.30), AAA_26 (PF13500.13), GATase_3 (PF07685.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP97
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Hydrogenobyrinate a,c-diamide synthase |
| EC (curated) |
EC 6.3.5.9
|
| Curated function | Catalyzes the ATP-dependent amidation of the two carboxylate groups at positions a and c of hydrogenobyrinate, using either L-glutamine or ammonia as the nitrogen source. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobB |
| eggNOG description | Catalyzes the ATP-dependent amidation of the two carboxylate groups at positions a and c of hydrogenobyrinate, using either L-glutamine or ammonia as the nitrogen source |
| Orthologous group | COG1797 |
| EC number |
EC 6.3.5.11, EC 6.3.5.9
|
| KEGG orthology |
K02224
|
| KEGG pathways |
map00860, map01100, map01120
|
| 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) pseudogene candidate
| pN/pS | 0.473 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 5 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 25.78% of strains (37434) · 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 |
|---|---|---|---|---|
CbiA | PF01656.30 | 5.3e-21 | 6–193 | CobQ/CobB/MinD/ParA nucleotide binding domain |
AAA_26 | PF13500.13 | 3.7e-07 | 109–189 | AAA domain |
GATase_3 | PF07685.21 | 6.2e-25 | 256–435 | CobB/CobQ-like glutamine amidotransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobO (cob(I)alamin adenosyltransferase), high confidence from genomic context alone (score 996 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2849c cobO |
cob(I)alamin adenosyltransferase | 999 | 996 ctx | neighborhood:881 cooccurence:611 database:900 textmining:850 |
Rv2065 cobH |
precorrin-8X methylmutase | 997 | 994 ctx | fusion:547 cooccurence:767 coexpression:408 database:900 textmining:653 |
Rv2062c cobN |
cobalamin biosynthesis protein CobN | 982 | 965 ctx | cooccurence:507 database:900 textmining:519 |
Rv2231c cobC |
aminotransferase | 963 | 960 ctx | fusion:900 cooccurence:427 |
Rv0255c cobQ1 |
cobyric acid synthase | 968 | 958 ctx | fusion:667 cooccurence:766 coexpression:426 |
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase | 959 | 912 ctx | cooccurence:755 coexpression:463 textmining:554 |
Rv1314c |
cob(I)yrinic acid a,c-diamide adenosyltransferase | 915 | 908 | database:900 |
Rv2850c |
magnesium chelatase | 988 | 903 ctx | neighborhood:857 textmining:889 |
Rv2207 cobT |
nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase | 922 | 899 ctx | fusion:497 cooccurence:623 coexpression:440 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 940 | 879 ctx | cooccurence:771 coexpression:406 textmining:533 |
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 931 | 879 ctx | cooccurence:624 coexpression:649 textmining:457 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 899 | 869 ctx | cooccurence:771 |
Rv2851c |
GCN5-like N-acetyltransferase | 981 | 860 ctx | neighborhood:857 textmining:870 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 921 | 850 ctx | neighborhood:721 cooccurence:477 textmining:499 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 934 | 822 ctx | cooccurence:699 textmining:647 |
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: cobyrinic acid A,C-diamide synthase
- MTBC0 PGAP product: cobyrinate a%2Cc-diamide synthase
- Pfam (hmmscan --cut_ga): CbiA PF01656.30 (E=5e-21), AAA_26 PF13500.13 (E=4e-07), GATase_3 PF07685.21 (E=6e-25)
- (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_217364.1)
- Domains: Pfam-A via hmmscan --cut_ga — CbiA (PF01656.30), AAA_26 (PF13500.13), 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
COG1797 - Curated reference: UniProt P9WP97 (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
cobO - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003027|Rv2848c|cobB MRVSAVAVAAPASGSGKTTIATGLIGALRQAGHTVAPFKVGPDFIDPGYHALAAGRPGRNLDPVLVGERLIGPLYAHGVAGADIAVIEGVLGLFDGRIGPAGGAPAAGSTAHVAALLGAPVILVVDARGQSHSVAALLHGFSTFDTATRIAGVILNRVGSARHEQVLRQACDQAGVAVLGAIPRTAELELPTRYLGLVTAVEYGRRARLAVQAMTAVVARHVDLAAVIACAGSQAAHPPWDPVIAVGNTARQPATVAIAAGRAFTFGYAEHAEMLRAAGAEVVEFDPLSETLPEGTDAVVLPGGFPEQFTAELSANDTVRRQINELAAAGAPVHAECAGLLYLVSELDGHPMCGVVAGSARFTQHLKLGYRDAVAVVDSALYSVGERVVGHEFHRTAVTFADSYQPAWVYQGQDVDDVRDGAVHSGVHASYLHTHPAATPGAVARFVAHAACNTPRA