Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pyruvate carboxylase |
|---|
| MTBC0 PGAP re-annotation | pyruvate carboxylase |
|---|
| Revised (this work) | Pyruvate carboxylase. Pfam: Biotin_carb_N (PF00289.29), CPSase_L_D2 (PF02786.23), Dala_Dala_lig_C (PF07478.19), Biotin_carb_C (PF02785.26), HMGL-like (PF00682.26), PYC_OADA (PF02436.24), Biotin_lipoyl (PF00364.29). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YEU0
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | Pyruvate carboxylase |
|---|
| EC (curated) |
EC 6.4.1.1
|
|---|
| Curated function | Catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|
| Preferred name | pyc |
|---|
| eggNOG description | Catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second |
|---|
| Orthologous group | COG1038 |
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| EC number |
EC 6.4.1.1
|
|---|
| KEGG orthology |
K01958
|
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| KEGG pathways |
map00020, map00620, map00720, map01100, map01120, map01200, map01230
|
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| KEGG modules |
M00173
|
|---|
| Gene Ontology (61) |
GO:0003674, GO:0003824, GO:0004075, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006629, GO:0006631, GO:0006633 +49 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 |
0.357 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
10 synonymous, 10 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 |
|---|
Biotin_carb_N | PF00289.29 |
2.5e-39 | 1–111 |
Biotin carboxylase, N-terminal domain |
CPSase_L_D2 | PF02786.23 |
6.1e-66 | 117–323 |
Carbamoyl-phosphate synthase L chain, ATP binding domain |
Dala_Dala_lig_C | PF07478.19 |
5.1e-06 | 144–291 |
D-ala D-ala ligase C-terminus |
Biotin_carb_C | PF02785.26 |
1.0e-34 | 339–446 |
Biotin carboxylase C-terminal domain |
HMGL-like | PF00682.26 |
2.0e-11 | 681–795 |
HMGL-like |
PYC_OADA | PF02436.24 |
1.7e-59 | 820–1010 |
Conserved carboxylase domain |
Biotin_lipoyl | PF00364.29 |
4.2e-14 | 1068–1125 |
Biotin-requiring enzyme |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1131 prpC |
methylcitrate synthase PrpC |
967 |
935 |
database:900 textmining:512 |
Rv0896 gltA2 |
citrate synthase 1 |
966 |
935 |
database:900 textmining:498 |
Rv0889c citA |
citrate synthase 2 |
961 |
929 |
database:900 textmining:486 |
Rv1617 pykA |
pyruvate kinase |
982 |
927 |
database:900 textmining:774 |
Rv1240 mdh |
malate dehydrogenase |
978 |
926 |
database:900 textmining:726 |
Rv2332 mez |
malate oxidoreductase |
987 |
919 |
database:900 textmining:848 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta |
926 |
917 |
database:900 |
Rv2852c mqo |
malate:quinone oxidoreductase |
935 |
913 |
database:900 |
Rv0211 pckA |
phosphoenolpyruvate carboxykinase |
980 |
906 |
database:900 textmining:806 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK |
914 |
906 |
database:900 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD |
912 |
906 |
database:900 |
Rv1872c lldD2 |
L-lactate dehydrogenase |
911 |
906 |
database:900 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha |
910 |
906 |
database:900 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component |
930 |
902 |
database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA |
939 |
901 |
database:900 textmining:414 |
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: pyruvate carboxylase
- MTBC0 PGAP product: pyruvate carboxylase
- Pfam (hmmscan --cut_ga): Biotin_carb_N PF00289.29 (E=2e-39), CPSase_L_D2 PF02786.23 (E=6e-66), Dala_Dala_lig_C PF07478.19 (E=5e-06), Biotin_carb_C PF02785.26 (E=1e-34), HMGL-like PF00682.26 (E=2e-11), PYC_OADA PF02436.24 (E=2e-59), Biotin_lipoyl PF00364.29 (E=4e-14)
- (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_217483.1)
- Domains: Pfam-A via hmmscan --cut_ga — Biotin_carb_N (PF00289.29), CPSase_L_D2 (PF02786.23), Dala_Dala_lig_C (PF07478.19), Biotin_carb_C (PF02785.26), HMGL-like (PF00682.26), PYC_OADA (PF02436.24), Biotin_lipoyl (PF00364.29)
- 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
COG1038
- Curated reference: UniProt
I6YEU0
(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 —
75 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003151|Rv2967c|pca
MFSKVLVANRGEIAIRAFRAAYELGVGTVAVYPYEDRNSQHRLKADESYQIGDIGHPVHAYLSVDEIVATARRAGADAIYPGYGFLSENPDLAAACAAAGISFVGPSAEVLELAGNKSRAIAAAREAGLPVLMSSAPSASVDELLSVAAGMPFPLFVKAVAGGGGRGMRRVGDIAALPEAIEAASREAESAFGDPTVYLEQAVINPRHIEVQILADNLGDVIHLYERDCSVQRRHQKVIELAPAPHLDAELRYKMCVDAVAFARHIGYSCAGTVEFLLDERGEYVFIEMNPRVQVEHTVTEEITDVDLVASQLRIAAGETLEQLGLRQEDIAPHGAALQCRITTEDPANGFRPDTGRISALRTAGGAGVRLDGSTNLGAEISPYFDSMLVKLTCRGRDLPTAVSRARRAIAEFRIRGVSTNIPFLQAVLDDPDFRAGRVTTSFIDERPQLLTARASADRGTKILNFLADVTVNNPYGSRPSTIYPDDKLPDLDLRAAPPAGSKQRLVKLGPEGFARWLRESAAVGVTDTTFRDAHQSLLATRVRTSGLSRVAPYLARTMPQLLSVECWGGATYDVALRFLKEDPWERLATLRAAMPNICLQMLLRGRNTVGYTPYPEIVTSAFVQEATATGIDIFRIFDALNNIESMRPAIDAVRETGSAIAEVAMCYTGDLTDPGEQLYTLDYYLKLAEQIVDAGAHVLAIKDMAGLLRPPAAQRLVSALRSRFDLPVHLHTHDTPGGQLASYVAAWHAGADAVDGAAAPLAGTTSQPALSSIVAAAAHTEYDTGLSLSAVCALEPYWEALRKVYAPFESGLPGPTGRVYHHEIPGGQLSNLRQQAIALGLGDRFEEIEEAYAGADRVLGRLVKVTPTSKVVGDLALALVGAGVSADEFASDPARFGIPESVLGFLRGELGDPPGGWPEPLRTAALAGRGAARPTAQLAADDEIALSSVGAKRQATLNRLLFPSPTKEFNEHREAYGDTSQLSANQFFYGLRQGEEHRVKLERGVELLIGLEAISEPDERGMRTVMCILNGQLRPVLVRDRSIASAVPAAEKADRGNPGHIAAPFAGVVTVGVCVGERVGAGQTIATIEAMKMEAPITAPVAGTVERVAVSDTAQVEGGDLLVVVS
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