ephA Resolved · high auto-curated

H37Rv Rv3617 · MTBC0 mtbc0_003834 · 322 aa · 4081437–4082405 (+) · RefSeq NP_218134.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)epoxide hydrolase EphA
MTBC0 PGAP re-annotationepoxide hydrolase EphA
Revised (this work)Epoxide hydrolase EphA. Pfam: Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14).

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

Curated reference (UniProt)

UniProt I6YGS0 SwissProt · reviewed · Evidence at protein level
UniProt nameEpoxide hydrolase A
EC (curated) EC 3.3.2.10
Curated functionCould be involved in detoxification of extraneous host-cell epoxides. Catalyzes the hydrolysis of epoxide-containing substrates.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred nameephA
eggNOG descriptionAlpha beta hydrolase
Orthologous groupCOG2267
Gene Ontology (107) GO:0000287, GO:0001676, GO:0002532, GO:0002538, GO:0002539, GO:0003008, GO:0003013, GO:0003674, GO:0003824, GO:0004301, GO:0005102, GO:0005488 +95 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 0.173 · 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)

PfamAccessioni-EvalueResiduesDescription
Abhydrolase_1PF00561.27 1.6e-2527–130 alpha/beta hydrolase fold
Hydrolase_4PF12146.16 5.6e-1328–156 Serine aminopeptidase, S33
Abhydrolase_6PF12697.14 8.2e-2129–311 Alpha/beta hydrolase family

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

Closest characterised functional partner: Rv3618 (monooxygenase), high confidence from genomic context alone (score 964 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3618 monooxygenase 964 964 ctx neighborhood:789 coexpression:803
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 533 506 experimental:441
Rv1527c pks5 polyketide synthase 528 501 experimental:441
Rv2048c pks12 polyketide synthase 528 500 experimental:441
Rv2940c mas multifunctional mycocerosic acid synthase 526 499 experimental:441
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 526 498 experimental:441
Rv0554 bpoC non-heme bromoperoxidase BpoC 463 463 ctx cooccurence:463
Rv2946c pks1 polyketide synthase 486 455
Rv0983 pepD serine protease PepD 451 450
Rv0125 pepA serine protease PepA 451 450
Rv1834 lipZ hydrolase 441 441 ctx cooccurence:436
Rv1181 pks4 polyketide beta-ketoacyl synthase 454 430
Rv1661 pks7 polyketide synthase 452 428
Rv1663 pks17 polyketide synthase 435 414
Rv1393c monoxygenase 415 328

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: epoxide hydrolase EphA
  • MTBC0 PGAP product: epoxide hydrolase EphA
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=2e-25), Hydrolase_4 PF12146.16 (E=6e-13), Abhydrolase_6 PF12697.14 (E=8e-21)
  • (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_218134.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14)
  • 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 COG2267
  • Curated reference: UniProt I6YGS0 (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 — 23 functional partner(s); context anchor Rv3618
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003834|Rv3617|ephA
MGAPTERLVDTNGVRLRVVEAGEPGAPVVILAHGFPELAYSWRHQIPALADAGYHVLAPDQRGYGGSSRPEAIEAYDIHRLTADLVGLLDDVGAERAVWVGHDWGAVVVWNAPLLHADRVAAVAALSVPALPRAQVPPTQAFRSRFGENFFYILYFQEPGIADAELNGDPARTMRRMIGGLRPPGDQSAAMRMLAPGPDGFIDRLPEPAGLPAWISQEELDHYIGEFTRTGFTGGLNWYRNFDRNWETTADLAGKTISVPSLFIAGTADPVLTFTRTDRAAEVISGPYREVLIDGAGHWLQQERPGEVTAALLEFLTGLELR