DhlA is the haloalkane dehalogenase of Xanthobacter autotrophicus GJ10, an alpha/beta-hydrolase-fold enzyme that hydrolytically cleaves carbon-halogen bonds in short halogenated aliphatic compounds, giving the corresponding primary alcohol, a halide ion and a proton. It requires no cofactor and uses an Asp-His-Asp catalytic triad in which the aspartate attacks the substrate carbon directly to form a covalent alkyl-enzyme intermediate that is then hydrolysed, a mechanism established by crystallography of trapped intermediates. Specificity covers terminally mono- and di-chlorinated and brominated alkanes up to C4, with highest activity on 1,2-dichloroethane, 1,3-dichloropropane and 1,2-dibromoethane. It catalyses the first of four steps that let X. autotrophicus GJ10 grow on 1,2-dichloroethane, a high-volume commodity chemical used in vinyl chloride manufacture, as sole carbon source. DhlA belongs to the same structural superfamily as epoxide hydrolases, which share the alpha/beta-hydrolase fold and a comparable nucleophile-His-acid triad, and that shared fold is the source of a misleading family-based annotation on this entry.
The preferred accession for this review is P22643. These relationships are manually assessed.
Reviewed 2026-10-19 · Searched: UP001161920, UP001603991
Retain P22643 as the primary Swiss-Prot accession. Both exact-taxon reference proteomes were searched as a deduplicated union. The leading alpha/beta-hydrolase hits are remote (about 25% global identity) and do not establish haloalkane dehalogenase identity or substrate specificity. The source is strain GJ10; no supported counterpart was identified in either reference proteome.
MMseqs2 searched 9,703 sequences across UP001161920, UP001603991 at E <= 1e-5 and sensitivity 7.5, returning 9 hits. Every returned sequence was globally aligned using BLOSUM62 with gap-open -10 and extension -0.5. Scores and sequences for all 9 returned candidates are retained, with 9 detailed alignment files. The heuristic search does not establish genomic absence or unique locus identity.
file:XANAU/dhlA/dhlA-record-evidence.yaml
target_sequence_count: 9703
file:XANAU/dhlA/dhlA-record-evidence.yaml
candidate_count: 9
The primary accession is outside every searched exact-taxon reference proteome.
file:XANAU/dhlA/dhlA-record-evidence.yaml
primary_in_any_reference_proteome: false
Sampled UniSave observations: 14-OCT-2015, entry version 97.: no Proteomes cross-reference; 02-DEC-2020, entry version 110.: no Proteomes cross-reference; 27-NOV-2024, entry version 122.: no Proteomes cross-reference. These dated observations do not establish uninterrupted membership/absence, the exact change date, or UniProt's motivation.
file:XANAU/dhlA/dhlA-record-evidence.yaml
entry_date: 14-OCT-2015, entry version 97. proteomes: []
file:XANAU/dhlA/dhlA-record-evidence.yaml
entry_date: 02-DEC-2020, entry version 110. proteomes: []
file:XANAU/dhlA/dhlA-record-evidence.yaml
entry_date: 27-NOV-2024, entry version 122. proteomes: []
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Root catalytic activity term from the epoxide hydrolase-like InterPro signature; the least informative possible molecular function statement. Reason: GO:0003824 is the root of the molecular function catalytic branch and is an ancestor of the specific haloalkane dehalogenase activity already annotated. IPR000639 is the epoxide hydrolase-like signature, which matches because DhlA shares the alpha/beta-hydrolase fold; mapping it only to the root is the conservative and correct choice for a signature whose members span several reaction types, but it contributes nothing for a gene with a solved structure and mechanism. |
| GO:0004301 epoxide hydrolase activity | IEA GO_REF:0000118 | REMOVE | Summary: TreeGrafter propagation of epoxide hydrolase activity onto a haloalkane dehalogenase; a fold-level transfer to the wrong reaction. Reason: Epoxide hydrolases and haloalkane dehalogenases share the alpha/beta-hydrolase fold and an analogous nucleophile-His-acid triad, so they group together in sequence-based family trees, but they catalyse different reactions on different substrates: an epoxide hydrolase opens a strained C-O-C ring to a diol, whereas DhlA displaces a halide from a saturated carbon. DhlA's substrate range was mapped directly and consists of halogenated alkanes; no epoxide is reported as a substrate, and the enzyme's covalent alkyl-enzyme mechanism is specific to halide displacement. This is the same failure mode as the GO:0016810 annotation on AtzA: a structural signature predicting the superfamily's prevalent chemistry rather than the member's own. Where the PAINT or TreeGrafter node genuinely covers both activities, the fix belongs at the node, not on this gene. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000107240 · PTN000107240 SUPPORTS SOURCE BUT NOT TARGET The node is appropriate for alpha/beta-hydrolase-fold epoxide hydrolases, but DhlA's demonstrated reaction is hydrolytic dehalogenation of haloalkanes, a different chemistry on a different substrate class within the same fold. |
| GO:0018786 haloalkane dehalogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The correct specific activity, converged on by a dedicated InterPro signature, a Rhea exactMatch, EC and a UniRule. Reason: RHEA:19081 (1-haloalkane + H2O = halide + primary alcohol) is an exactMatch of GO:0018786 and RHEA:25185 (the 1,2-dichloroethane reaction) is a narrowMatch of the same term, which is the correct arrangement: the specific reaction maps as a narrowMatch to a term defined over the substrate class, rather than being pushed up to an EC-level grouping class. This is the pattern the RHEA:25968 case on GO:0016616 should follow. The activity itself has been characterized structurally and mechanistically; as with tfdA and pcpB, no experimental annotation exists in GOA despite that. |
| GO:0019260 1,2-dichloroethane catabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway-mapped process term; DhlA is step 1 of 4 in a pathway supporting growth on 1,2-dichloroethane. Reason: X. autotrophicus GJ10 was isolated for growth on 1,2-dichloroethane as sole carbon source, and DhlA catalyses the committed first step, converting it to 2-chloroethanol en route to glycolate. The process annotation reflects the host's demonstrated catabolic capability rather than inference from the activity alone. |
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Download this section (compressed HTML)Q: Does the PANTHER node PTN000107240 genuinely cover both epoxide hydrolases and haloalkane dehalogenases, and if so should the epoxide hydrolase assertion be moved to a descendant node? The fix for this propagation belongs upstream, not as a per-gene removal.
Q: How many other alpha/beta-hydrolase-fold enzymes carry epoxide hydrolase annotations by family inference alone? The fold is large and functionally heterogeneous, so this may be a recurring pattern rather than a single case.
Q: Is there a natural haloalkane substrate for DhlA? Biogenic halomethanes and haloethanes are produced in marine and soil environments, which would make an ancient origin plausible.
Experiment: Assay purified DhlA against biogenic short-chain haloalkanes (for example bromomethane, chloromethane, bromoethane) and against a panel of epoxides, to test both the ancestral-substrate hypothesis and the epoxide hydrolase annotation directly.
Hypothesis: DhlA turns over at least one biogenic haloalkane efficiently and shows no detectable epoxide hydrolase activity, supporting both an ancient dehalogenase function and removal of the propagated epoxide hydrolase term.
Type: enzyme kinetics
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