echA21 Family assigned · medium auto-curated

H37Rv Rv3774 · MTBC0 mtbc0_004001 · 274 aa · 4242970–4243794 (+) · RefSeq NP_218291.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)enoyl-CoA hydratase EchA21
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 P75019 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible enoyl-CoA hydratase EchA21

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred nameechA21
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 (14) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005739, GO:0005777, GO:0042579, GO:0043226, GO:0043227, GO:0043229, GO:0043231, GO:0044424 +2 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 0.191 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 4 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 3.8e-4011–273 Enoyl-CoA hydratase/isomerase
ECH_2PF16113.11 1.1e-1518–200 Enoyl-CoA hydratase/isomerase

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

Closest characterised functional partner: lipE (lipase LipE), high confidence from genomic context alone (score 878 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3775 lipE lipase LipE 877 878 ctx neighborhood:872
Rv0468 fadB2 3-hydroxybutyryl-CoA dehydrogenase 882 871 database:650
Rv0154c fadE2 acyl-CoA dehydrogenase FadE2 854 846 database:750
Rv0400c fadE7 acyl-CoA dehydrogenase FadE7 854 845 database:750
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 853 845 database:750
Rv0231 fadE4 acyl-CoA dehydrogenase FadE4 850 845 database:750
Rv1715 fadB3 3-hydroxybutyryl-CoA dehydrogenase FadB 882 844 database:650
Rv0131c fadE1 acyl-CoA dehydrogenase FadE1 853 844 database:750
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 853 844 database:750
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 852 844 database:750
Rv0860 fadB fatty oxidation protein FadB 887 800 database:650 textmining:462
Rv3773c hyp hypothetical protein 792 792 ctx neighborhood:790
Rv2524c fas fatty acid synthase 816 789 coexpression:646
Rv0243 fadA2 acetyl-CoA acetyltransferase FadA 773 752 coexpression:401 database:447
Rv1074c fadA3 beta-ketoacyl CoA thiolase FadA 761 751 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 EchA21
  • MTBC0 PGAP product: crotonase/enoyl-CoA hydratase family protein
  • Pfam (hmmscan --cut_ga): ECH_1 PF00378.26 (E=4e-40), ECH_2 PF16113.11 (E=1e-15)
  • (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_218291.1)
  • 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 P75019 (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 — 156 functional partner(s); context anchor lipE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004001|Rv3774|echA21
MGETYESVTVETKDQVAQVTLIGPGKGNAMGPAFWSEMPEVFHALDADREVRAIVITGSGKNFSYGLDVPAMGGMFAPLIADGALARPRTDFHTEILRMQKAINAVADCRTPTIAAVQGWCIGGAVDLISAVDIRYASADAKFSVREVKLAIVADMGSLARLPLILSDGHLRELALTGKNIDAARAEKIGLVNDVYDDADQTLAAAHATAAEIAANPPLAVYGIKDVLDQQRTSAVSENLRYVAAWNAAFLPSKDLTEGISATFAKRPPQFTGE