HemBB is one of two KT2440 delta-aminolevulinate dehydratase paralogs. It is an ALAD-family enzyme predicted to condense two 5-aminolevulinate molecules into porphobilinogen. Its sequence retains the conserved Schiff-base lysines and a predicted magnesium-binding site but lacks the catalytic zinc-site prediction present in HemB, suggesting a distinct metal-site architecture.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004655 porphobilinogen synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This is the specific predicted catalytic function of HemBB. Reason: UniProt assigns EC 4.2.1.24, the ALAD family, conserved Schiff-base active sites, and a magnesium-binding residue. The assignment remains predictive because no KT2440 paralog-specific assay was identified. Supporting Evidence: file:PSEPK/hemBB/hemBB-uniprot.txt RecName: Full=Delta-aminolevulinic acid dehydratase |
| GO:0005829 cytosol | IEA GO_REF:0000118 | ACCEPT | Summary: A soluble cytosolic location is consistent with the ALAD-family architecture. Reason: No signal peptide or transmembrane segment is predicted, and UniProt retains the TreeGrafter cytosol cross-reference. Supporting Evidence: file:PSEPK/hemBB/hemBB-uniprot.txt GO; GO:0005829; C:cytosol; |
| GO:0006779 porphyrin-containing compound biosynthetic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: This is a correct broad pathway assignment for an early shared tetrapyrrole step. Reason: Predicted porphobilinogen formation supplies the common tetrapyrrole trunk. The annotation is biologically correct, while the catalytic activity and direct tetrapyrrole role are the more informative core claims. Supporting Evidence: file:PSEPK/hemBB/hemBB-uniprot.txt PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX |
| GO:0006783 heme biosynthetic process | IEA GO_REF:0000118 | ACCEPT | Summary: Predicted ALAD activity places HemBB in the heme-b precursor pathway. Reason: Its predicted porphobilinogen product feeds the shared reactions leading to uroporphyrinogen III, protoporphyrin IX, and heme b. Supporting Evidence: file:PSEPK/hemBB/hemBB-uniprot.txt KW Heme biosynthesis |
| GO:0008270 zinc ion binding | IEA GO_REF:0000118 | MODIFY | Summary: The transferred zinc annotation does not match the metal-site prediction for HemBB. Reason: The current HemBB record predicts Mg2+ binding at residue 247 and does not identify the catalytic Zn2+-ligand triad found in HemB. Magnesium ion binding is therefore the conservative sequence-supported replacement. Proposed replacements: magnesium ion binding Supporting Evidence: file:PSEPK/hemBB/hemBB-uniprot.txt ligand="Mg(2+)" |
| GO:0033014 tetrapyrrole biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: Predicted HemBB activity directly participates in tetrapyrrole biosynthesis. Reason: An active ALAD paralog would produce porphobilinogen for the shared tetrapyrrole trunk. The process term is appropriately broad given that HemBB's relative physiological contribution remains unresolved. Supporting Evidence: file:PSEPK/hemBB/hemBB-uniprot.txt PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic metal binding is compatible with the predicted magnesium site. Reason: GO:0046872 is true if the predicted Mg2+ site is functional, but it is less informative than the magnesium-ion-binding replacement proposed for the unsupported zinc transfer. Supporting Evidence: file:PSEPK/hemBB/hemBB-uniprot.txt ligand="Mg(2+)" |
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Download this section (compressed HTML)Q: Does HemBB operate under a distinct metal or environmental regime from the zinc-site-containing HemB paralog?
Experiment: Compare purified HemBB and HemB kinetics and metal dependence, then test single and double mutants across zinc and magnesium availability.
Hypothesis: HemBB is an active Mg-dependent ALAD paralog rather than an inactive duplicate.
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