HemB is one of two KT2440 delta-aminolevulinate dehydratase paralogs. It is an ALAD-family enzyme predicted to condense two 5-aminolevulinate molecules into porphobilinogen. Sequence-based site annotation identifies catalytic zinc ligands, a magnesium-binding site, and the conserved lysines that form Schiff-base intermediates, supporting a metal-dependent porphobilinogen synthase role in heme-b precursor synthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004655 porphobilinogen synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This is the specific predicted catalytic function of HemB. Reason: UniProt assigns EC 4.2.1.24, the ALAD family, conserved catalytic Schiff-base sites, and metal-binding residues consistent with porphobilinogen synthase activity. Supporting Evidence: file:PSEPK/hemB/hemB-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/hemB/hemB-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: Porphobilinogen formation supplies the common tetrapyrrole trunk. The annotation is biologically correct, but the catalytic activity and direct tetrapyrrole-biosynthesis role are more informative core claims. Supporting Evidence: file:PSEPK/hemB/hemB-uniprot.txt PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX |
| GO:0006783 heme biosynthetic process | IEA GO_REF:0000118 | ACCEPT | Summary: ALAD activity supplies porphobilinogen to the shared heme-b pathway. Reason: The reaction is required upstream of hydroxymethylbilane, uroporphyrinogen III, and all subsequent heme-b intermediates. Supporting Evidence: file:PSEPK/hemB/hemB-uniprot.txt KW Heme biosynthesis |
| GO:0008270 zinc ion binding | IEA GO_REF:0000118 | ACCEPT | Summary: HemB contains a predicted catalytic zinc site characteristic of one ALAD lineage. Reason: Three residues are annotated as catalytic Zn2+ ligands, and the sequence contains the corresponding cysteine-rich region. This architecture is absent from the KT2440 HemBB paralog. Supporting Evidence: file:PSEPK/hemB/hemB-uniprot.txt ligand_note="catalytic" |
| GO:0033014 tetrapyrrole biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: HemB directly participates in tetrapyrrole biosynthesis. Reason: ALAD produces porphobilinogen for the shared tetrapyrrole trunk, so the broad process term is accurate and does not force a single downstream tetrapyrrole endpoint. Supporting Evidence: file:PSEPK/hemB/hemB-uniprot.txt PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | MODIFY | Summary: The broad metal call can be replaced by the additional predicted magnesium site. Reason: Zinc binding is already represented by GO:0008270, while UniProt also identifies a distinct Mg2+-binding residue. GO:0000287 records that second metal requirement without retaining a generic parent term. Proposed replacements: magnesium ion binding Supporting Evidence: file:PSEPK/hemB/hemB-uniprot.txt ligand="Mg(2+)" |
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Download this section (compressed HTML)Q: Is HemB the principal aerobic ALAD isozyme, and how does its zinc site affect activity relative to HemBB?
Experiment: Purify both proteins and compare kinetics, oligomerization, and metal dependence, then phenotype single and double mutants with ALA rescue.
Hypothesis: HemB and HemBB are active ALAD paralogs with different metal dependence.
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