cobU Resolved · high auto-curated
H37Rv Rv0254c · MTBC0 mtbc0_000270 ·
174 aa · 306207–306731 (-) ·
RefSeq NP_214768.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase |
| Revised (this work) | Bifunctional adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase. Pfam: CobU (PF02283.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53676
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Adenosylcobinamide kinase |
| EC (curated) |
EC 2.7.1.156, EC 2.7.7.62
|
| Curated function | Catalyzes ATP-dependent phosphorylation of adenosylcobinamide and addition of GMP to adenosylcobinamide phosphate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobU |
| eggNOG description | cobinamide kinase |
| Orthologous group | COG2087 |
| EC number |
EC 2.7.1.156, EC 2.7.7.62
|
| KEGG orthology |
K02231
|
| 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 | 0.13 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (381) · 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 |
|---|---|---|---|---|
CobU | PF02283.23 | 4.8e-48 | 3–174 | Cobinamide kinase / cobinamide phosphate guanyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobT (nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2207 cobT |
nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase | 996 | 994 ctx | neighborhood:461 fusion:899 cooccurence:768 coexpression:557 textmining:421 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 995 | 990 ctx | neighborhood:461 cooccurence:772 database:900 textmining:539 |
Rv0255c cobQ1 |
cobyric acid synthase | 998 | 989 ctx | neighborhood:757 fusion:640 cooccurence:769 coexpression:525 textmining:845 |
Rv2236c cobD |
cobalamin biosynthesis transmembrane protein CobD | 998 | 988 ctx | cooccurence:764 coexpression:459 database:900 textmining:845 |
Rv2849c cobO |
cob(I)alamin adenosyltransferase | 998 | 967 ctx | cooccurence:636 database:900 textmining:965 |
Rv1314c |
cob(I)yrinic acid a,c-diamide adenosyltransferase | 933 | 908 | database:900 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 931 | 879 ctx | cooccurence:624 coexpression:649 textmining:457 |
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase | 877 | 707 | coexpression:407 textmining:600 |
Rv0256c PPE2 |
PPE family protein PPE2 | 891 | 693 ctx | neighborhood:690 textmining:660 |
Rv2065 cobH |
precorrin-8X methylmutase | 881 | 673 ctx | cooccurence:427 textmining:654 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 954 | 634 ctx | cooccurence:461 textmining:880 |
Rv2135c hyp |
hypothetical protein | 571 | 546 ctx | cooccurence:419 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 971 | 523 | textmining:943 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 725 | 476 | textmining:498 |
Rv2206 |
transmembrane protein | 461 | 461 ctx | neighborhood:461 |
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: bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase
- MTBC0 PGAP product: bifunctional adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase
- Pfam (hmmscan --cut_ga): CobU PF02283.23 (E=5e-48)
- (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_214768.1)
- Domains: Pfam-A via hmmscan --cut_ga — CobU (PF02283.23)
- 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
COG2087 - Curated reference: UniProt O53676 (TrEMBL, unreviewed; 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
cobT - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000270|Rv0254c|cobU MRILVTGGVRSGKSTHAEALLGDAADVVYVAPGRPAAGSDPDWDARVALHRARRPPTWLTVETADVATALSEARSPVLVDCLGTWLTAIMDGEALWSAATADVYAVLEARLDGLCAALTGLPTAIVVTNEVGLGVVPSHSSGVLFRDLLGTINRRVAAVCDEVHLVIAGRVLKL