cofC Resolved · high auto-curated
H37Rv Rv2983 · MTBC0 mtbc0_003168 ·
214 aa · 3360427–3361071 (+) ·
RefSeq NP_217499.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 2-phospho-L-lactate guanylyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | 2-phospho-L-lactate guanylyltransferase |
| Revised (this work) | 2-phospho-L-lactate guanylyltransferase. Pfam: CofC (PF01983.22), NTP_transf_3 (PF12804.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP83
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phosphoenolpyruvate guanylyltransferase |
| EC (curated) |
EC 2.7.7.105
|
| Curated function | Guanylyltransferase that catalyzes the activation of phosphoenolpyruvate (PEP) as enolpyruvoyl-2-diphospho-5'-guanosine, via the condensation of PEP with GTP. It is involved in the biosynthesis of coenzyme F420, a hydride carrier cofactor. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cofC |
| eggNOG description | Guanylyltransferase that catalyzes the activation of 2- phospho-L-lactate (LP) as (2S)-lactyl-2-diphospho-5'-guanosine (LPPG), via the condensation of LP with GTP. Is involved in the biosynthesis of coenzyme F420, a hydride carrier cofactor |
| Orthologous group | COG1920 |
| EC number |
EC 2.7.7.68
|
| KEGG orthology |
K14941
|
| KEGG pathways |
map00680, map01120
|
| KEGG modules |
M00378
|
| Gene Ontology (17) |
GO:0003674, GO:0003824, GO:0006732, GO:0008150, GO:0008152, GO:0009058, GO:0009108, GO:0009987, GO:0016740, GO:0016772, GO:0016779, GO:0043814 +5 more
|
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 | 0.39 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 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 |
|---|---|---|---|---|
CofC | PF01983.22 | 1.7e-12 | 12–166 | Guanylyl transferase CofC like |
NTP_transf_3 | PF12804.14 | 2.7e-08 | 42–160 | MobA-like NTP transferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fbiA (2-phospho-L-lactate transferase), high confidence from genomic context alone (score 979 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3261 fbiA |
2-phospho-L-lactate transferase | 998 | 979 ctx | cooccurence:773 database:900 textmining:948 |
Rv3262 fbiB |
coenzyme F420:L-glutamate ligase | 992 | 784 ctx | cooccurence:742 textmining:965 |
Rv2984 ppk1 |
polyphosphate kinase | 779 | 779 ctx | neighborhood:777 |
Rv3547 ddn |
deazaflavin-dependent nitroreductase | 902 | 731 ctx | cooccurence:723 textmining:651 |
Rv1261c hyp |
hypothetical protein | 774 | 726 ctx | cooccurence:722 |
Rv0132c fgd2 |
F420-dependent glucose-6-phosphate dehydrogenase | 795 | 712 ctx | cooccurence:700 |
Rv3178 |
nitroreductase | 740 | 709 ctx | cooccurence:700 |
Rv1558 hyp |
hypothetical protein | 773 | 702 ctx | cooccurence:694 |
Rv0407 fgd1 |
F420-dependent glucose-6-phosphate dehydrogenase | 970 | 689 ctx | cooccurence:677 textmining:909 |
Rv2951c |
phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase | 699 | 668 ctx | cooccurence:657 |
Rv2985 mutT1 |
8-oxo-dGTP diphosphatase | 653 | 654 ctx | neighborhood:654 |
Rv2982c gpdA2 |
glycerol-3-phosphate dehydrogenase | 634 | 635 ctx | neighborhood:628 |
Rv1855c |
oxidoreductase | 650 | 614 ctx | cooccurence:600 |
Rv1173 fbiC |
FO synthase | 978 | 609 ctx | cooccurence:560 textmining:948 |
Rv0044c |
oxidoreductase | 637 | 600 ctx | cooccurence:584 |
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: 2-phospho-L-lactate guanylyltransferase
- MTBC0 PGAP product: 2-phospho-L-lactate guanylyltransferase
- Pfam (hmmscan --cut_ga): CofC PF01983.22 (E=2e-12), NTP_transf_3 PF12804.14 (E=3e-08)
- (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_217499.1)
- Domains: Pfam-A via hmmscan --cut_ga — CofC (PF01983.22), NTP_transf_3 (PF12804.14)
- 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
COG1920 - Curated reference: UniProt P9WP83 (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 —
29 functional partner(s); context anchor
fbiA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003168|Rv2983|cofC MSGTPDDGDIGLIIAVKRLAAAKTRLAPVFSAQTRENVVLAMLVDTLTAAAGVGSLRSITVITPDEAAAAAAAGLGADVLADPTPEDDPDPLNTAITAAERVVAEGASNIVVLQGDLPALQTQELAEAISAARHHRRSFVADRLGTGTAVLCAFGTALHPRFGPDSSARHRRSGAVELTGAWPGLRCDVDTPADLTAARQLGVGPATARAVAHR