mhpE Resolved · high auto-curated
H37Rv Rv3469c · MTBC0 mtbc0_003686 ·
336 aa · 3912013–3913023 (-) ·
RefSeq NP_217986.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 4-hydroxy-2-oxovalerate aldolase MhpE |
|---|---|
| MTBC0 PGAP re-annotation | 4-hydroxy-2-oxovalerate aldolase |
| Revised (this work) | 4-hydroxy-2-oxovalerate aldolase. Pfam: HMGL-like (PF00682.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06334
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Oxaloacetate decarboxylase |
| EC (curated) |
EC 4.1.1.112
|
| Curated function | Exhibits oxaloacetate decarboxylase activity. Lacks any detectable aldolase activity with 4-hydroxy-2-oxopentanoate (HOPA), 4-hydroxy-2-oxohexanoate (HOHA) or other 4-hydroxy-2-oxoacids. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | mhpE |
| eggNOG description | Catalyzes the retro-aldol cleavage of 4-hydroxy-2- oxopentanoate to pyruvate and acetaldehyde. Is involved in the meta-cleavage pathway for the degradation of aromatic compounds |
| Orthologous group | COG0119 |
| EC number |
EC 4.1.3.39
|
| KEGG orthology |
K01666
|
| KEGG pathways |
map00360, map00362, map00621, map00622, map01100, map01120, map01220
|
| KEGG modules |
M00545, M00569
|
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 | 2.013 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 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 |
|---|---|---|---|---|
HMGL-like | PF00682.26 | 9.8e-37 | 11–261 | HMGL-like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hsaG (acetaldehyde dehydrogenase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3535c hsaG |
acetaldehyde dehydrogenase | 999 | 1000 ctx | cooccurence:774 experimental:987 database:900 |
Rv3536c hsaE |
hydratase | 985 | 983 ctx | cooccurence:755 database:900 |
Rv3534c hsaF |
4-hydroxy-2-oxovalerate aldolase | 923 | 923 | database:900 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 986 | 906 ctx | neighborhood:677 coexpression:439 textmining:860 |
Rv3468c |
dTDP-glucose 4,6-dehydratase | 906 | 906 ctx | neighborhood:882 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 789 | 767 | coexpression:694 |
Rv2988c leuC |
3-isopropylmalate dehydratase large subunit | 781 | 758 | coexpression:695 |
Rv2987c leuD |
3-isopropylmalate dehydratase small subunit | 780 | 757 | coexpression:695 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 765 | 740 | coexpression:691 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 745 | 718 | coexpression:650 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 722 | 708 | |
Rv0812 |
4-amino-4-deoxychorismate lyase | 683 | 663 | coexpression:608 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 681 | 661 | coexpression:606 |
Rv3002c ilvN |
acetolactate synthase small subunit | 690 | 656 | coexpression:582 |
Rv3471c hyp |
hypothetical protein | 649 | 649 ctx | neighborhood:646 |
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: 4-hydroxy-2-oxovalerate aldolase MhpE
- MTBC0 PGAP product: 4-hydroxy-2-oxovalerate aldolase
- Pfam (hmmscan --cut_ga): HMGL-like PF00682.26 (E=1e-36)
- (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_217986.1)
- Domains: Pfam-A via hmmscan --cut_ga — HMGL-like (PF00682.26)
- 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
COG0119 - Curated reference: UniProt O06334 (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 —
110 functional partner(s); context anchor
hsaG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003686|Rv3469c|mhpE MLMTATHREPIVLDTTVRDGSYAVNFQYTDDDVRRIVGDLDAAGIPYIEIGHGVTIGAAAAQGPAAHTDEEYFRAARSVVRNARLGAVIVPALARIETVDLAGDYLDFLRICVIATEFELVMPFVERAQSKGLEVSIQLVKSHLFEPDVLAAAGKRARDVGVRIVYVVDTTGTFLPEDARRYVEALRGASDVSVGFHGHNNLAMAVANTLEAFDAGADFLDGTLMGFGRGAGNCQIECLVAALQRRGHLAAVDLDRIFDAARSDMLGRSPQSYGIDPWEISFGFHGLDSLQVEHLRAAAQQAGLSVSHVIRQTAKSHAGQWLSPQDIDRVVVGMRA