hemC

Summary: This is the specific core catalytic function of HemC.

Reason: UniProt assigns EC 2.5.1.61 and describes tetrapolymerization of porphobilinogen into hydroxymethylbilane.

Summary: Cytoplasmic localization is consistent with this soluble bacterial enzyme.

Reason: HemC belongs to the HMBS (porphobilinogen deaminase) family (HAMAP MF_00260, Pfam Porphobil_deam), whose bacterial members are soluble cytoplasmic enzymes. The UniProt record has no TRANSMEM, SIGNAL or lipoprotein feature and no CC SUBCELLULAR LOCATION line (checked and empty), so there is no export or membrane signal; cytoplasm rests on that absence plus family membership, not on a localization assay.

Summary: HemC is an obligatory middle enzyme in the protoporphyrin route to heme b.

Reason: The HemC reaction generates the linear tetrapyrrole precursor required for uroporphyrinogen III and all downstream heme-b intermediates.

Summary: The annotation is true; HemC builds the first linear tetrapyrrole of the shared trunk.

Reason: HemC polymerizes porphobilinogen into hydroxymethylbilane, a step of the tetrapyrrole trunk that feeds heme, siroheme and cobalamin, so the tetrapyrrole biosynthetic process term is accurate. This review earlier proposed GO:0006780 uroporphyrinogen III biosynthetic process instead; that was withdrawn for consistency with the E. coli hemC, human HMBS and yeast HEM3 reviews, which accept GO:0033014 and reserve GO:0006780 for the cyclization step that GO annotates to uroporphyrinogen-III synthase.