Rv2296 Resolved · high auto-curated

H37Rv Rv2296 · MTBC0 mtbc0_002436 · 300 aa · 2592253–2593155 (+) · RefSeq NP_216812.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)haloalkane dehalogenase
MTBC0 PGAP re-annotationhaloalkane dehalogenase
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.

Curated reference (UniProt)

UniProt P9WMS3 SwissProt · reviewed · Evidence at protein level
UniProt nameHaloalkane dehalogenase 1
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 namedhmA
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 (8) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944

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 1.364 · 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
Abhydrolase_1PF00561.27 1.2e-2847–284 alpha/beta hydrolase fold
Abhydrolase_6PF12697.14 1.1e-1249–291 Alpha/beta hydrolase family

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

Closest characterised functional partner: tadA (cytidine/deoxycytidylate deaminase), high confidence from genomic context alone (score 833 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2579 dhaA haloalkane dehalogenase 926 927 database:900
Rv1833c dhmA2 haloalkane dehalogenase 925 925 database:900
Rv0162c adhE1 zinc-type alcohol dehydrogenase subunit E 912 912 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
Rv3752c tadA cytidine/deoxycytidylate deaminase 833 833 ctx fusion:830
Rv2297 hyp hypothetical protein 733 733 ctx neighborhood:717
Rv1124 ephC epoxide hydrolase EphC 615 615 ctx cooccurence:615
Rv2295 hyp hypothetical protein 594 594 ctx neighborhood:581
Rv3733c hyp hypothetical protein 546 546 ctx neighborhood:544
Rv3171c hpx non-heme haloperoxidase Hpx 545 546 ctx cooccurence:543
Rv2940c mas multifunctional mycocerosic acid synthase 530 502 experimental:441
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 529 501 experimental:441
Rv2048c pks12 polyketide synthase 529 501 experimental:441

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: haloalkane dehalogenase
  • MTBC0 PGAP product: haloalkane dehalogenase
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=1e-28), Abhydrolase_6 PF12697.14 (E=1e-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 NP_216812.1)
  • 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 P9WMS3 (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 — 33 functional partner(s); context anchor tadA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002436|Rv2296|
MDVLRTPDSRFEHLVGYPFAPHYVDVTAGDTQPLRMHYVDEGPGDGPPIVLLHGEPTWSYLYRTMIPPLSAAGHRVLAPDLIGFGRSDKPTRIEDYTYLRHVEWVTSWFENLDLHDVTLFVQDWGSLIGLRIAAEHGDRIARLVVANGFLPAAQGRTPLPFYVWRAFARYSPVLPAGRLVNFGTVHRVPAGVRAGYDAPFPDKTYQAGARAFPRLVPTSPDDPAVPANRAAWEALGRWDKPFLAIFGYRDPILGQADGPLIKHIPGAAGQPHARIKASHFIQEDSGTELAERMLSWQQAT