cobS Resolved · high auto-curated
H37Rv Rv2208 · MTBC0 mtbc0_002344 ·
249 aa · 2498650–2499399 (+) ·
RefSeq NP_216724.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | adenosylcobinamide-GDP ribazoletransferase |
|---|---|
| MTBC0 PGAP re-annotation | adenosylcobinamide-GDP ribazoletransferase |
| Revised (this work) | Adenosylcobinamide-GDP ribazoletransferase. Pfam: CobS (PF02654.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP91
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Adenosylcobinamide-GDP ribazoletransferase |
| EC (curated) |
EC 2.7.8.26
|
| Curated function | Joins adenosylcobinamide-GDP and alpha-ribazole to generate adenosylcobalamin (Ado-cobalamin). Also synthesizes adenosylcobalamin 5'-phosphate from adenosylcobinamide-GDP and alpha-ribazole 5'-phosphate (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobS |
| eggNOG description | Joins adenosylcobinamide-GDP and alpha-ribazole to generate adenosylcobalamin (Ado-cobalamin). Also synthesizes adenosylcobalamin 5'-phosphate from adenosylcobinamide-GDP and alpha-ribazole 5'-phosphate |
| Orthologous group | COG0368 |
| EC number |
EC 2.7.8.26
|
| KEGG orthology |
K02233
|
| 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 | 1.288 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 |
|---|---|---|---|---|
CobS | PF02654.21 | 2.6e-44 | 8–240 | Cobalamin-5-phosphate synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobT (nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase), high confidence from genomic context alone (score 992 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2207 cobT |
nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase | 995 | 992 ctx | neighborhood:882 cooccurence:772 coexpression:467 database:500 textmining:500 |
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 995 | 990 ctx | neighborhood:461 cooccurence:772 database:900 textmining:539 |
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase | 991 | 982 | coexpression:963 textmining:554 |
Rv2849c cobO |
cob(I)alamin adenosyltransferase | 996 | 974 ctx | cooccurence:676 database:900 textmining:888 |
Rv2228c |
multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase | 962 | 944 | database:900 |
Rv1314c |
cob(I)yrinic acid a,c-diamide adenosyltransferase | 920 | 908 | database:900 |
Rv0255c cobQ1 |
cobyric acid synthase | 946 | 900 ctx | cooccurence:772 coexpression:508 textmining:485 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 872 | 814 ctx | cooccurence:770 |
Rv2206 |
transmembrane protein | 787 | 787 ctx | neighborhood:786 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 964 | 784 ctx | cooccurence:730 textmining:843 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 819 | 764 ctx | cooccurence:563 coexpression:410 |
Rv1487 hyp |
hypothetical protein | 749 | 750 | coexpression:749 |
Rv1570 bioD |
ATP-dependent dethiobiotin synthetase BioD | 776 | 747 | coexpression:746 |
Rv2231c cobC |
aminotransferase | 768 | 729 | database:500 |
Rv2070c cobK |
precorrin-6A reductase | 789 | 725 | coexpression:654 |
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: adenosylcobinamide-GDP ribazoletransferase
- MTBC0 PGAP product: adenosylcobinamide-GDP ribazoletransferase
- Pfam (hmmscan --cut_ga): CobS PF02654.21 (E=3e-44)
- (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_216724.1)
- Domains: Pfam-A via hmmscan --cut_ga — CobS (PF02654.21)
- 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
COG0368 - Curated reference: UniProt P9WP91 (SwissProt, reviewed; Inferred from homology)
- 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 —
37 functional partner(s); context anchor
cobT - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002344|Rv2208|cobS MMRSLATAFAFATVIPTPGSATTPMGRGPMTALPVVGAALGALAAAIAWAGAQVFGPSSPLSGMLTVAVLLVVTRGLHIDGVADTADGLGCYGPPQRALAVMRDGSTGPFGVAAVVLVIALQGLAFATLTTVGIAGITLAVLSGRVTAVLVCRRSVPAAHGSTLGSRVAGTQPAPVVAAWLAVLLAVSVPAGPRPWQGPIAVLVAVTAGAALAAHCVHRFGGVTGDVLGSAIELSTTVSAVTLAGLARL