cobD Resolved · high auto-curated
H37Rv Rv2236c · MTBC0 mtbc0_002376 ·
313 aa · 2534592–2535533 (-) ·
RefSeq NP_216752.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cobalamin biosynthesis transmembrane protein CobD |
|---|---|
| MTBC0 PGAP re-annotation | cobalamin biosynthesis protein |
| Revised (this work) | Cobalamin biosynthesis protein. Pfam: CobD_Cbib (PF03186.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP93
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cobalamin biosynthesis protein CobD |
| Curated function | Converts cobyric acid to cobinamide by the addition of aminopropanol on the F carboxylic group. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cobD |
| eggNOG description | Converts cobyric acid to cobinamide by the addition of aminopropanol on the F carboxylic group |
| Orthologous group | COG1270 |
| EC number |
EC 6.3.1.10
|
| KEGG orthology |
K02227
|
| KEGG pathways |
map00860, map01100
|
| KEGG modules |
M00122
|
| Gene Ontology (7) |
GO:0005575, GO:0005576, 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)
| pN/pS | 0.615 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
CobD_Cbib | PF03186.19 | 2.6e-90 | 14–292 | CobD/Cbib protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobU (bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase), high confidence from genomic context alone (score 988 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 998 | 988 ctx | cooccurence:764 coexpression:459 database:900 textmining:845 |
Rv0255c cobQ1 |
cobyric acid synthase | 994 | 981 ctx | cooccurence:774 database:900 textmining:734 |
Rv2849c cobO |
cob(I)alamin adenosyltransferase | 995 | 972 ctx | cooccurence:684 database:900 textmining:842 |
Rv1314c |
cob(I)yrinic acid a,c-diamide adenosyltransferase | 915 | 908 | database:900 |
Rv2065 cobH |
precorrin-8X methylmutase | 900 | 870 ctx | cooccurence:732 coexpression:458 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 899 | 869 ctx | cooccurence:771 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 872 | 814 ctx | cooccurence:770 |
Rv2207 cobT |
nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase | 852 | 806 ctx | cooccurence:761 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 977 | 794 ctx | cooccurence:564 coexpression:404 textmining:896 |
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase | 940 | 786 ctx | cooccurence:647 textmining:734 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 835 | 785 ctx | cooccurence:749 |
Rv2237 hyp |
hypothetical protein | 779 | 779 ctx | neighborhood:778 |
Rv2070c cobK |
precorrin-6A reductase | 743 | 664 ctx | cooccurence:526 |
Rv3859c gltB |
glutamate synthase large subunit | 544 | 544 ctx | neighborhood:544 |
Rv2231c cobC |
aminotransferase | 544 | 480 |
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: cobalamin biosynthesis transmembrane protein CobD
- MTBC0 PGAP product: cobalamin biosynthesis protein
- Pfam (hmmscan --cut_ga): CobD_Cbib PF03186.19 (E=3e-90)
- (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_216752.1)
- Domains: Pfam-A via hmmscan --cut_ga — CobD_Cbib (PF03186.19)
- 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
COG1270 - Curated reference: UniProt P9WP93 (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 —
22 functional partner(s); context anchor
cobU - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002376|Rv2236c|cobD MFASTWQTRAVGVLIGCLLDVVFGDPKRGHPVALFGRAAAKLEQITYRDGRVAGAVHVGLLVGAVGLLGAALQRLPGRCWPVAATATATWAALGGTSLARTGRQISDLLERDDVEAARRLLPSLCGRDPAQLGGPGLTRAALESVAENTADAQVVPLLWAASSGVPAVLGYRAINTLDSMIGYRSPRYLRFGWAAARLDDWANYVGARATAVLVVICAPVVGGSPRGAVRAWRRDAARHPSPNAGVVEAAFAGALDVRLGGPTRYHHELQIRPTLGDGRSPKVADLRRAVVLSRVVQAGAAVLAVMLVYRRRP