hsaE Resolved · high auto-curated
H37Rv Rv3536c · MTBC0 mtbc0_003753 ·
261 aa · 3998188–3998973 (-) ·
RefSeq NP_218053.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hydratase |
|---|---|
| MTBC0 PGAP re-annotation | 2-keto-4-pentenoate hydratase |
| Revised (this work) | 2-keto-4-pentenoate hydratase. Pfam: FAA_hydrolase (PF01557.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6XHH5
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable hydratase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mhpD |
| eggNOG description | hydratase |
| Orthologous group | COG3971 |
| EC number |
EC 4.2.1.80
|
| KEGG orthology |
K02554
|
| 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 | 0.171 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 |
|---|---|---|---|---|
FAA_hydrolase | PF01557.24 | 3.5e-12 | 93–257 | Fumarylacetoacetate (FAA) hydrolase C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hsaF (4-hydroxy-2-oxovalerate aldolase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3534c hsaF |
4-hydroxy-2-oxovalerate aldolase | 999 | 998 ctx | neighborhood:879 cooccurence:771 database:900 textmining:880 |
Rv3535c hsaG |
acetaldehyde dehydrogenase | 999 | 996 ctx | neighborhood:879 cooccurence:772 coexpression:852 textmining:828 |
Rv3469c mhpE |
4-hydroxy-2-oxovalerate aldolase MhpE | 985 | 983 ctx | cooccurence:755 database:900 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 901 | 746 ctx | neighborhood:676 textmining:630 |
Rv3569c hsaD |
4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase | 886 | 693 | database:500 textmining:645 |
Rv3538 |
dehydrogenase | 694 | 682 ctx | neighborhood:676 |
Rv3533c PPE62 |
PPE family protein PPE62 | 546 | 547 ctx | neighborhood:542 |
Rv3568c hsaC |
extradiol dioxygenase | 701 | 456 ctx | cooccurence:420 textmining:474 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 636 | 308 | textmining:496 |
Rv1937 |
oxygenase | 470 | 306 | |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 754 | 285 | textmining:671 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 639 | 274 | textmining:524 |
Rv0687 |
NAD-dependent oxidoreductase | 510 | 101 | textmining:478 |
Rv3567c hsaB |
flavin-dependent monooxygenase reductase subunit HsaB | 688 | 86 | textmining:674 |
Rv3515c fadD19 |
acyl-CoA synthetase | 529 | 79 | textmining:510 |
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: hydratase
- MTBC0 PGAP product: 2-keto-4-pentenoate hydratase
- Pfam (hmmscan --cut_ga): FAA_hydrolase PF01557.24 (E=4e-12)
- (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_218053.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAA_hydrolase (PF01557.24)
- 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
COG3971 - Curated reference: UniProt I6XHH5 (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 —
23 functional partner(s); context anchor
hsaF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003753|Rv3536c|hsaE MLRDATRDELAADLAQAERSRDPIGQLTAAHPEIDVVDAYEIQLINIRQRVAEGARVVGHKVGLSSPIMQQMMGVDEPDYGHLLDDMQVFEDTPVQASRYLSPRVEVEVGFILAADLPGAGCTEDDVLAATEALVPAIELIDTRIKDWQIKICDTIADNASAAGFVLGAARVPPADLDVRAIDAKLTRNGEVVAEGRSDAVLGNPATAVAWLAGKVESFGVRLRKGDIVLPGSCTFAVEARAGDEFVADFTGLGLVRLSFE