prpC Resolved · high auto-curated
H37Rv Rv1131 · MTBC0 mtbc0_001214 ·
393 aa · 1264572–1265753 (+) ·
RefSeq NP_215647.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | methylcitrate synthase PrpC |
|---|---|
| MTBC0 PGAP re-annotation | 2-methylcitrate synthase |
| Revised (this work) | 2-methylcitrate synthase. Pfam: Citrate_synt (PF00285.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y9Q3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2-methylcitrate synthase |
| EC (curated) |
EC 2.3.3.16, EC 2.3.3.5
|
| Curated function | Involved in the catabolism of short chain fatty acids (SCFA) via the tricarboxylic acid (TCA)(acetyl degradation route) and via the 2-methylcitrate cycle I (propionate degradation route). Catalyzes the Claisen condensation of propionyl-CoA and oxaloacetate (OAA) to yield 2-methylcitrate (2-MC) and CoA. Also catalyzes the condensation of oxaloacetate with acetyl-CoA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | prpC |
| eggNOG description | Belongs to the citrate synthase family |
| Orthologous group | COG0372 |
| EC number |
EC 2.3.3.1, EC 2.3.3.5
|
| KEGG orthology |
K01647, K01659
|
| KEGG pathways |
map00020, map00630, map00640, map01100, map01110, map01120, map01130, map01200, map01210, map01230
|
| KEGG modules |
M00009, M00010, M00012, M00740
|
| Gene Ontology (26) |
GO:0003674, GO:0003824, GO:0006082, GO:0006629, GO:0006631, GO:0008150, GO:0008152, GO:0009987, GO:0016740, GO:0016746, GO:0016999, GO:0017144 +14 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 | 0.262 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 4 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 |
|---|---|---|---|---|
Citrate_synt | PF00285.27 | 8.7e-126 | 31–377 | Citrate synthase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prpD (2-methylcitrate dehydratase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1130 prpD |
2-methylcitrate dehydratase | 999 | 998 ctx | neighborhood:881 cooccurence:674 coexpression:929 database:500 textmining:906 |
Rv1475c acn |
iron-regulated aconitate hydratase | 995 | 993 ctx | cooccurence:489 coexpression:690 database:941 textmining:411 |
Rv1240 mdh |
malate dehydrogenase | 989 | 979 | coexpression:648 experimental:423 database:900 textmining:515 |
Rv3667 acs |
acetyl-CoAsynthetase | 974 | 969 | coexpression:649 database:900 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 958 | 955 | coexpression:424 database:900 |
Rv1837c glcB |
malate synthase | 981 | 948 | coexpression:435 database:900 textmining:653 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 971 | 945 | coexpression:912 textmining:504 |
Rv2852c mqo |
malate:quinone oxidoreductase | 974 | 941 | coexpression:412 database:900 textmining:590 |
Rv2967c pca |
pyruvate carboxylase | 967 | 935 | database:900 textmining:512 |
Rv0889c citA |
citrate synthase 2 | 938 | 934 | database:900 |
Rv0896 gltA2 |
citrate synthase 1 | 923 | 920 | database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 934 | 907 | database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 913 | 905 | database:900 |
Rv0211 pckA |
phosphoenolpyruvate carboxykinase | 944 | 901 | database:900 textmining:460 |
Rv1098c fum |
fumarate hydratase | 958 | 895 | coexpression:418 database:800 textmining:622 |
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: methylcitrate synthase PrpC
- MTBC0 PGAP product: 2-methylcitrate synthase
- Pfam (hmmscan --cut_ga): Citrate_synt PF00285.27 (E=9e-126)
- (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_215647.1)
- Domains: Pfam-A via hmmscan --cut_ga — Citrate_synt (PF00285.27)
- 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
COG0372 - Curated reference: UniProt I6Y9Q3 (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 —
134 functional partner(s); context anchor
prpD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001214|Rv1131|prpC MTGPLAAARSVAATKSMTAPTVDERPDIKKGLAGVVVDTTAISKVVPQTNSLTYRGYPVQDLAARCSFEQVAFLLWRGELPTDAELALFSQRERASRRVDRSMLSLLAKLPDNCHPMDVVRTAISYLGAEDPDEDDAAANRAKAMRMMAVLPTIVAIDMRRRRGLPPIAPHSGLGYAQNFLHMCFGEVPETAVVSAFEQSMILYAEHGFNASTFAARVVTSTQSDIYSAVTGAIGALKGRLHGGANEAVMHDMIEIGDPANAREWLRAKLARKEKIMGFGHRVYRHGDSRVPTMKRALERVGTVRDGQRWLDIYQVLAAEMASATGILPNLDFPTGPAYYLMGFDIASFTPIFVMSRITGWTAHIMEQATANALIRPLSAYCGHEQRVLPGTF