echA2 Family assigned · medium auto-curated

H37Rv Rv0456c · MTBC0 mtbc0_000478 · 304 aa · 549254–550168 (-) · RefSeq NP_214970.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)enoyl-CoA hydratase EchA2
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 O07179 TrEMBL · unreviewed · Evidence at protein level
UniProt nameEnoyl-CoA hydratase EchA2
Curated functionCould possibly oxidize fatty acids using specific components.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred nameechA2
eggNOG descriptionBelongs to the enoyl-CoA hydratase isomerase family
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

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 0.547 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 5 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.65% of strains (938) · 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)

PfamAccessioni-EvalueResiduesDescription
ECH_1PF00378.26 2.8e-2816–239 Enoyl-CoA hydratase/isomerase
ECH_2PF16113.11 5.9e-1718–212 Enoyl-CoA hydratase/isomerase

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0231 fadE4 acyl-CoA dehydrogenase FadE4 853 848 database:750
Rv0131c fadE1 acyl-CoA dehydrogenase FadE1 851 845 database:750
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 850 845 database:750
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 859 844 database:750
Rv0154c fadE2 acyl-CoA dehydrogenase FadE2 849 844 database:750
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 849 844 database:750
Rv0400c fadE7 acyl-CoA dehydrogenase FadE7 849 844 database:750
Rv0455c hyp hypothetical protein 796 796 ctx neighborhood:795
Rv2524c fas fatty acid synthase 816 789 coexpression:646
Rv1715 fadB3 3-hydroxybutyryl-CoA dehydrogenase FadB 764 755 database:650
Rv0468 fadB2 3-hydroxybutyryl-CoA dehydrogenase 763 754 database:650
Rv0860 fadB fatty oxidation protein FadB 764 752 database:650
Rv1074c fadA3 beta-ketoacyl CoA thiolase FadA 761 751 database:447
Rv0859 fadA acyltransferase 760 751 database:447
Rv3556c fadA6 acetyl-CoA acetyltransferase FadA 760 750 database:447

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 EchA2
  • MTBC0 PGAP product: crotonase/enoyl-CoA hydratase family protein
  • Pfam (hmmscan --cut_ga): ECH_1 PF00378.26 (E=3e-28), ECH_2 PF16113.11 (E=6e-17)
  • (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_214970.1)
  • 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 O07179 (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 — 141 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000478|Rv0456c|echA2
MPTPDFQTLLYTTAGPVATITLNRPEQLNTIVPPMPDEIEAAIGLAERDQDIKVIVLRGAGRAFSGGYDFGGGFQHWGDAMMTDGRWDPGKDFAMVTARETGPTQKFMAIWRASKPVIAQVHGWCVGGASDYALCADIVIASEDAVIGTPYSRMWGAYLTGMWLYRLSLAKVKWHSLTGRPLTGVQAAEAELINEAVPFERLEARVAEIATELARIPLSQLQAQKLIVNQAYENMGLASTQLLGGILDGLMRNTPDALEFIRTAQTQGVRAAVERRDGPFGDYSQAPPELRPDPTHVITPDGSM