Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phosphoenolpyruvate carboxykinase |
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| MTBC0 PGAP re-annotation | phosphoenolpyruvate carboxykinase (GTP) |
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| Revised (this work) | Phosphoenolpyruvate carboxykinase (GTP). Pfam: PEPCK_N (PF17297.8), PEPCK_GTP (PF00821.24). |
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Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIH3
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Phosphoenolpyruvate carboxykinase [GTP] |
|---|
| EC (curated) |
EC 4.1.1.32
|
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| Curated function | Involved in the gluconeogenesis, in growth on fatty acids and is important for initiation of infection in the macrophages. Catalyzes the GTP-dependent conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
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| Preferred name | pckG |
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| eggNOG description | Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle |
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| Orthologous group | COG1274 |
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| EC number |
EC 4.1.1.32
|
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| KEGG orthology |
K01596
|
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| KEGG pathways |
map00010, map00020, map00620, map01100, map01110, map01120, map01130, map03320, map04068, map04151, map04152, map04910, map04920, map04922, map04931, map04964
|
|---|
| KEGG modules |
M00003
|
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| Gene Ontology (59) |
GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006873, GO:0006875, GO:0006879, GO:0006950 +47 more
|
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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 |
1.078 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 7 missense, 0 nonsense, 0 frameshift
|
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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 |
|---|
PEPCK_N | PF17297.8 |
1.1e-101 | 22–241 |
Phosphoenolpyruvate carboxykinase N-terminal domain |
PEPCK_GTP | PF00821.24 |
1.8e-172 | 245–604 |
Phosphoenolpyruvate carboxykinase C-terminal P-loop domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA |
959 |
944 |
coexpression:730 database:800 |
Rv2967c pca |
pyruvate carboxylase |
980 |
906 |
database:900 textmining:806 |
Rv1617 pykA |
pyruvate kinase |
956 |
904 |
database:900 textmining:563 |
Rv1240 mdh |
malate dehydrogenase |
953 |
903 |
database:900 textmining:539 |
Rv2852c mqo |
malate:quinone oxidoreductase |
925 |
903 |
database:900 |
Rv0896 gltA2 |
citrate synthase 1 |
925 |
902 |
database:900 |
Rv0889c citA |
citrate synthase 2 |
924 |
902 |
database:900 |
Rv1131 prpC |
methylcitrate synthase PrpC |
944 |
901 |
database:900 textmining:460 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK |
934 |
900 |
database:900 |
Rv1023 eno |
enolase |
918 |
900 |
database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB |
902 |
890 |
coexpression:474 database:800 |
Rv3667 acs |
acetyl-CoAsynthetase |
855 |
831 |
database:800 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component |
845 |
811 |
database:800 |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase |
817 |
809 |
database:800 |
Rv0234c gabD1 |
succinate-semialdehyde dehydrogenase |
817 |
809 |
database:800 |
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: phosphoenolpyruvate carboxykinase
- MTBC0 PGAP product: phosphoenolpyruvate carboxykinase (GTP)
- Pfam (hmmscan --cut_ga): PEPCK_N PF17297.8 (E=1e-101), PEPCK_GTP PF00821.24 (E=2e-172)
- (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_214725.1)
- Domains: Pfam-A via hmmscan --cut_ga — PEPCK_N (PF17297.8), PEPCK_GTP (PF00821.24)
- 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
COG1274
- Curated reference: UniProt
P9WIH3
(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 —
56 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000225|Rv0211|pckA
MTSATIPGLDTAPTNHQGLLSWVEEVAELTQPDRVVFTDGSEEEFQRLCDQLVEAGTFIRLNPEKHKNSYLALSDPSDVARVESRTYICSAKEIDAGPTNNWMDPGEMRSIMKDLYRGCMRGRTMYVVPFCMGPLGAEDPKLGVEITDSEYVVVSMRTMTRMGKAALEKMGDDGFFVKALHSVGAPLEPGQKDVAWPCSETKYITHFPETREIWSYGSGYGGNALLGKKCYSLRIASAMAHDEGWLAEHMLILKLISPENKAYYFAAAFPSACGKTNLAMLQPTIPGWRAETLGDDIAWMRFGKDGRLYAVNPEFGFFGVAPGTNWKSNPNAMRTIAAGNTVFTNVALTDDGDVWWEGLEGDPQHLIDWKGNDWYFRETETNAAHPNSRYCTPMSQCPILAPEWDDPQGVPISGILFGGRRKTTVPLVTEARDWQHGVFIGATLGSEQTAAAEGKVGNVRRDPMAMLPFLGYNVGDYFQHWINLGKHADESKLPKVFFVNWFRRGDDGRFLWPGFGENSRVLKWIVDRIEHKAGGATTPIGTVPAVEDLDLDGLDVDAADVAAALAVDADEWRQELPLIEEWLQFVGEKLPTGVKDEFDALKERLG
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