htdZ Resolved · high auto-curated

H37Rv Rv0130 · MTBC0 mtbc0_000141 · 151 aa · 158193–158648 (+) · RefSeq NP_214644.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)3-hydroxyl-thioester dehydratase
MTBC0 PGAP re-annotation3-hydroxyacyl-thioester dehydratase HtdZ
Revised (this work)3-hydroxyacyl-thioester dehydratase HtdZ. Pfam: MaoC_dehydratas (PF01575.26), FAS1_DH_region (PF13452.12).

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

Curated reference (UniProt)

UniProt P9WNP3 SwissProt · reviewed · Evidence at protein level
UniProt name3-hydroxyacyl-thioester dehydratase Z
EC (curated) EC 4.2.1.-, EC 4.2.1.119, EC 4.2.1.55
Curated functionShows trans-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydratase activity. In vitro, can hydrate (2E)-butenoyl-CoA, (2E)-hexenoyl-CoA and (2E)-decenoyl-CoA.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptiondehydratase
Orthologous groupCOG2030
Gene Ontology (30) GO:0003674, GO:0003824, GO:0004300, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009987 +18 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 1.381 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 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
MaoC_dehydratasPF01575.26 1.5e-3411–131 MaoC like domain
FAS1_DH_regionPF13452.12 3.4e-0614–128 FAS1-like, dehydratase domain region

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

Closest characterised functional partner: fadB4 (NADPH quinone oxidoreductase FadB), high confidence from genomic context alone (score 811 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3141 fadB4 NADPH quinone oxidoreductase FadB 815 811 ctx fusion:741
Rv0149 quinone oxidoreductase 710 703 ctx fusion:575
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 667 650
Rv1934c fadE17 acyl-CoA dehydrogenase FadE17 659 642
Rv3339c icd1 isocitrate dehydrogenase 632 632 database:476
Rv0154c fadE2 acyl-CoA dehydrogenase FadE2 629 610
Rv3562 fadE31 acyl-CoA dehydrogenase FadE31 615 598
Rv3564 fadE33 acyl-CoA dehydrogenase FadE33 597 577
Rv3573c fadE34 acyl-CoA dehydrogenase FadE34 591 570
Rv0271c fadE6 acyl-CoA dehydrogenase FadE6 587 566
Rv0148 short-chain type dehydrogenase/reductase 583 565
Rv0860 fadB fatty oxidation protein FadB 588 562
Rv3761c fadE36 acyl-CoA dehydrogenase FadE36 572 556
Rv0125 pepA serine protease PepA 551 552 database:498
Rv1043c hyp hypothetical protein 550 550 database:498

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: 3-hydroxyl-thioester dehydratase
  • MTBC0 PGAP product: 3-hydroxyacyl-thioester dehydratase HtdZ
  • Pfam (hmmscan --cut_ga): MaoC_dehydratas PF01575.26 (E=1e-34), FAS1_DH_region PF13452.12 (E=3e-06)
  • (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_214644.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MaoC_dehydratas (PF01575.26), FAS1_DH_region (PF13452.12)
  • 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 COG2030
  • Curated reference: UniProt P9WNP3 (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 — 126 functional partner(s); context anchor fadB4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000141|Rv0130|htdZ
MRTFESVADLAAAAGEKVGQSDWVTITQEEVNLFADATGDHQWIHVDPERAAAGPFGTTIAHGFMTLALLPRLQHQMYTVKGVKLAINYGLNKVRFPAPVPVGSRVRATSSLVGVEDLGNGTVQATVSTTVEVEGSAKPACVAESIVRYVA