dhaA Resolved · high auto-curated

H37Rv Rv2579 · MTBC0 - · 300 aa · 2903639–2904541 (+) · RefSeq YP_177890.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)haloalkane dehalogenase
MTBC0 PGAP re-annotation
Revised (this work)Haloalkane dehalogenase. Pfam: Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WMR9 SwissProt · reviewed · Evidence at protein level
UniProt nameHaloalkane dehalogenase 3
EC (curated) EC 3.8.1.5
Curated functionCatalyzes hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namedhaA
eggNOG descriptionCatalyzes hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons
Orthologous groupCOG0596
EC number EC 3.8.1.5
KEGG orthology K01563
KEGG pathways map00361, map00625, map01100, map01120
Gene Ontology (32) GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006805, GO:0008150, GO:0008152, GO:0009056, GO:0009410, GO:0009987 +20 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 0.616 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.72% of strains (1048) · 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
Abhydrolase_1PF00561.27 2.6e-1932–279 alpha/beta hydrolase fold
Abhydrolase_6PF12697.14 6.7e-1233–283 Alpha/beta hydrolase family

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

Closest characterised functional partner: lipZ (hydrolase), medium confidence from genomic context alone (score 573 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1833c dhmA2 haloalkane dehalogenase 930 928 database:900
Rv2296 dhmA1 haloalkane dehalogenase 926 927 database:900
Rv0162c adhE1 zinc-type alcohol dehydrogenase subunit E 912 913 database:900
Rv0761c adhB alcohol dehydrogenase B 912 912 database:900
Rv1862 adhA alcohol dehydrogenase A 903 904 database:900
Rv1530 adh alcohol dehydrogenase 906 902 database:900
Rv2578c hyp hypothetical protein 598 599 ctx neighborhood:593
Rv1834 lipZ hydrolase 572 573 ctx cooccurence:570
Rv2627c hyp hypothetical protein 520 503
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 527 500 experimental:441
Rv1527c pks5 polyketide synthase 617 498 experimental:441
Rv2940c mas multifunctional mycocerosic acid synthase 526 498 experimental:441
Rv2048c pks12 polyketide synthase 526 498 experimental:441
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 526 498 experimental:441
Rv1124 ephC epoxide hydrolase EphC 482 482 ctx cooccurence:479

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): haloalkane dehalogenase
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=3e-19), Abhydrolase_6 PF12697.14 (E=7e-12)
  • (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 YP_177890.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), 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 COG0596
  • Curated reference: UniProt P9WMR9 (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 lipZ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2579|dhaA
MTAFGVEPYGQPKYLEIAGKRMAYIDEGKGDAIVFQHGNPTSSYLWRNIMPHLEGLGRLVACDLIGMGASDKLSPSGPDRYSYGEQRDFLFALWDALDLGDHVVLVLHDWGSALGFDWANQHRDRVQGIAFMEAIVTPMTWADWPPAVRGVFQGFRSPQGEPMALEHNIFVERVLPGAILRQLSDEEMNHYRRPFVNGGEDRRPTLSWPRNLPIDGEPAEVVALVNEYRSWLEETDMPKLFINAEPGAIITGRIRDYVRSWPNQTEITVPGVHFVQEDSPEEIGAAIAQFVRRLRSAAGV