echA19 Family assigned · medium auto-curated

H37Rv Rv3516 · MTBC0 mtbc0_003732 · 263 aa · 3976221–3977012 (+) · RefSeq NP_218033.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)enoyl-CoA hydratase EchA19
MTBC0 PGAP re-annotationcrotonase/enoyl-CoA hydratase family protein
Revised (this work)Crotonase/enoyl-CoA hydratase family protein. Pfam: ECH_1 (PF00378.26), ECH_2 (PF16113.11).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O53561 SwissProt · reviewed · Evidence at protein level
UniProt nameEnoyl-CoA hydratase EchA19
EC (curated) EC 4.2.1.-
Curated functionDegradation of the cholesterol side chain involves 3 multistep beta-oxidation cycles, this may be involved in the second cycle (Probable). Hydrates 3-OCDO-CoA ((22E)-3-oxo-chol-4,22-dien-24-oyl-CoA) to make (22R)-HOCO-CoA (3-oxo-chol-4-ene-(22R)-hydroxy-24-oyl-CoA). Also acts on octenoyl-CoA. Not active on (E)-3-OCDS-CoA ((E)-3-oxocholest-4,24-dien-26-oyl-CoA) or 3-OPDC-CoA (3-oxo-4,17-pregnadiene-20-carboxyl-CoA). Hydrates the same substrate as ChsH3, but the 2 enzymes make different stereoisomers of the product.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred nameechA19
eggNOG descriptionEnoyl-CoA hydratase
Orthologous groupCOG1024
EC number EC 4.2.1.17
KEGG orthology K01692
KEGG pathways map00071, map00280, map00281, map00310, map00360, map00362, map00380, map00410, map00627, map00640, map00650, map00903, map00930, map01100, map01110, map01120, map01130, map01212
KEGG modules M00032, M00087
Gene Ontology (47) GO:0003674, GO:0003824, GO:0004300, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005739, GO:0006082, GO:0006629, GO:0006631, GO:0006635 +35 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 0.676 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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)

PfamAccessioni-EvalueResiduesDescription
ECH_1PF00378.26 2.2e-5616–262 Enoyl-CoA hydratase/isomerase
ECH_2PF16113.11 1.3e-2717–195 Enoyl-CoA hydratase/isomerase

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: fadD19 (acyl-CoA synthetase), high confidence from genomic context alone (score 789 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0468 fadB2 3-hydroxybutyryl-CoA dehydrogenase 879 872 database:650
Rv1867 hyp hypothetical protein 863 856 ctx fusion:454 database:447
Rv3504 fadE26 acyl-CoA dehydrogenase FadE26 894 850 database:643
Rv1715 fadB3 3-hydroxybutyryl-CoA dehydrogenase FadB 897 845 database:650
Rv0131c fadE1 acyl-CoA dehydrogenase FadE1 852 845 database:750
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 852 845 database:750
Rv0154c fadE2 acyl-CoA dehydrogenase FadE2 851 844 database:750
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 851 844 database:750
Rv0400c fadE7 acyl-CoA dehydrogenase FadE7 851 844 database:750
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 851 844 database:750
Rv0231 fadE4 acyl-CoA dehydrogenase FadE4 849 844 database:750
Rv3522 ltp4 lipid transfer protein 970 840 database:447 textmining:826
Rv3505 fadE27 acyl-CoA dehydrogenase FadE27 876 819 database:643
Rv3523 ltp3 lipid carrier protein 973 813 database:447 textmining:865
Rv3515c fadD19 acyl-CoA synthetase 964 789 ctx neighborhood:607 textmining:836

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: enoyl-CoA hydratase EchA19
  • MTBC0 PGAP product: crotonase/enoyl-CoA hydratase family protein
  • Pfam (hmmscan --cut_ga): ECH_1 PF00378.26 (E=2e-56), ECH_2 PF16113.11 (E=1e-27)
  • (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_218033.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ECH_1 (PF00378.26), ECH_2 (PF16113.11)
  • 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 COG1024
  • Curated reference: UniProt O53561 (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 — 163 functional partner(s); context anchor fadD19
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003732|Rv3516|echA19
MESGPDALVERRGHTLIVTMNRPAARNALSTEMMRIMVQAWDRVDNDPDIRCCILTGAGGYFCAGMDLKAATQKPPGDSFKDGSYDPSRIDALLKGRRLTKPLIAAVEGPAIAGGTEILQGTDIRVAGESAKFGISEAKWSLYPMGGSAVRLVRQIPYTLACDLLLTGRHITAAEAKEMGLIGHVVPDGQALTKALELADAISANGPLAVQAILRSIRETECMPENEAFKIDTQIGIKVFLSDDAKEGPRAFAEKRAPNFQNR