prpD Resolved · high auto-curated
H37Rv Rv1130 · MTBC0 - ·
526 aa · 1254555–1256135 (+) ·
RefSeq NP_215646.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 2-methylcitrate dehydratase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | 2-methylcitrate dehydratase. Pfam: MmgE_PrpD_N (PF03972.20), MmgE_PrpD_C (PF19305.5). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O06582
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2-methylcitrate dehydratase |
| EC (curated) |
EC 4.2.1.3, EC 4.2.1.79
|
| 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 dehydration of 2-methylcitrate (2-MC) to yield the cis isomer of 2-methyl-aconitate. Could also catalyze the dehydration of citrate and the hydration of cis-aconitate (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | prpD |
| eggNOG description | MmgE/PrpD family |
| Orthologous group | COG2079 |
| EC number |
EC 4.2.1.79
|
| KEGG orthology |
K01720
|
| KEGG pathways |
map00640
|
| Gene Ontology (55) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006629, GO:0006631, GO:0008150 +43 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 | 0.363 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 9 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (171) · clonal |
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 |
|---|---|---|---|---|
MmgE_PrpD_N | PF03972.20 | 8.3e-67 | 45–285 | MmgE/PrpD N-terminal domain |
MmgE_PrpD_C | PF19305.5 | 6.3e-43 | 309–495 | MmgE/PrpD C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prpC (methylcitrate synthase PrpC), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1131 prpC |
methylcitrate synthase PrpC | 999 | 998 ctx | neighborhood:881 cooccurence:674 coexpression:929 database:500 textmining:906 |
Rv1129c prpR |
transcriptional regulator | 991 | 884 ctx | neighborhood:621 cooccurence:519 coexpression:415 textmining:928 |
Rv1132 hyp |
hypothetical protein | 788 | 789 ctx | neighborhood:783 |
Rv1998c hyp |
hypothetical protein | 804 | 744 | coexpression:723 |
Rv0896 gltA2 |
citrate synthase 1 | 740 | 570 | coexpression:515 textmining:420 |
Rv0465c ramB |
HTH-type transcriptional regulator | 763 | 540 ctx | cooccurence:474 textmining:507 |
Rv0889c citA |
citrate synthase 2 | 656 | 540 | coexpression:516 |
Rv2498c citE |
citrate (pro-3S)-lyase subunit beta | 543 | 524 | |
Rv1240 mdh |
malate dehydrogenase | 554 | 456 | coexpression:416 |
Rv3667 acs |
acetyl-CoAsynthetase | 528 | 448 | coexpression:403 |
Rv0974c accD2 |
acetyl-/propionyl-CoA carboxylase subunit beta | 441 | 442 | coexpression:423 |
Rv2502c accD1 |
acetyl-/propionyl-CoA carboxylase subunit beta | 439 | 440 | coexpression:421 |
Rv3280 accD5 |
propionyl-CoA carboxylase subunit beta | 496 | 438 | coexpression:419 |
Rv3799c accD4 |
propionyl-CoA carboxylase subunit beta AccD | 437 | 438 | coexpression:419 |
Rv2247 accD6 |
acetyl-/propionyl-CoA carboxylase subunit beta | 437 | 438 | coexpression:419 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): 2-methylcitrate dehydratase
- Pfam (hmmscan --cut_ga): MmgE_PrpD_N PF03972.20 (E=8e-67), MmgE_PrpD_C PF19305.5 (E=6e-43)
- (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_215646.1)
- Domains: Pfam-A via hmmscan --cut_ga — MmgE_PrpD_N (PF03972.20), MmgE_PrpD_C (PF19305.5)
- 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
COG2079 - Curated reference: UniProt O06582 (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 —
23 functional partner(s); context anchor
prpC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1130|prpD MPDQDTKVRFFRVFCWCPVLRMVRIMLMHAVRAWRSADDFPCTEHMAYKIAQVAADPVDVDPEVADMVCNRIIDNAAVSAASMVRRPVTVARHQALAHPVRHGAKVFGVEGSYSADWAAWANGVAARELDFHDTFLAADYSHPADNIPPLVAVAQQLGVCGAELIRGLVTAYEIHIDLTRGICLHEHKIDHVAHLGPAVAAGIGTMLRLDQETIYHAIGQALHLTTSTRQSRKGAISSWKAFAPAHAGKVGIEAVDRAMRGEGSPAPIWEGEDGVIAWLLAGPEHTYRVPLPAPGEPKRAILDSYTKQHSAEYQSQAPIDLACRLRERIGDLDQIASIVLHTSHHTHVVIGTGSGDPQKFDPDASRETLDHSLPYIFAVALQDGCWHHERSYAPERARRSDTVALWHKISTVEDPEWTRRYHCADPAKKAFGARAEVTLHSGEVIVDELAVADAHPLGTRPFERKQYVEKFTELADGVVEPVEQQRFLAVVESLADLESGAVGGLNVLVDPRVLDKAPVIPPGIFR