hemN

Summary: HemN is catalytic, but this root molecular-function term is uninformative.

Reason: GO:0051989 captures the specific radical-SAM coproporphyrinogen dehydrogenase reaction and should replace generic catalytic activity.

Proposed replacements: coproporphyrinogen dehydrogenase activity

Summary: This describes the pathway position but not HemN's specific radical-SAM chemistry.

Reason: The oxygen-independent EC 1.3.98.3 reaction is represented by GO:0051989, whereas GO:0004109 is used for the distinct HemF-type oxidase activity.

Proposed replacements: coproporphyrinogen dehydrogenase activity

Summary: Cytoplasmic localization is explicitly predicted for HemN.

Reason: UniProt assigns the soluble radical-SAM enzyme to the cytoplasm.

Summary: The pathway assignment is correct and can be made endpoint-specific for KT2440.

Reason: HemN forms protoporphyrinogen IX in the oxygen-independent late route leading to heme B, supporting the live endpoint term GO:0006785.

Proposed replacements: heme B biosynthetic process

Summary: This broad metal-binding term is correct but less informative than the cluster term.

Reason: Following the RADICAL_SAM project rule for the generic domain-derived rows (projects/RADICAL_SAM.md): a correct-but-general MF row is MODIFY, not KEEP_AS_NON_CORE. HemN's only recorded metal site is the [4Fe-4S] cluster, so the generic parent is replaced by GO:0051539, which this entry already carries.

Proposed replacements: 4 iron, 4 sulfur cluster binding

Summary: This parent is valid but less informative than the specific cluster-type term.

Reason: Following the RADICAL_SAM project rule for the generic domain-derived rows (projects/RADICAL_SAM.md): correct but general, and GO:0051539 entails it, so the parent row is replaced rather than retained as non-core. Same replacement as ECOLI/hemN.

Proposed replacements: 4 iron, 4 sulfur cluster binding

Summary: A [4Fe-4S] center is integral to radical-SAM catalysis by HemN.

Reason: Core cofactor binding under the project rule: the cluster is the catalytic cofactor that reductively cleaves SAM, not an accessory feature subordinate to the dehydrogenase term. Catalysis is established for HemN, so the row is ACCEPT. ECOLI/hemN ACCEPTs the identical row.

Summary: This is the most precise available molecular-function term for HemN.

Reason: UniProt assigns EC 1.3.98.3 and RHEA:15425, the radical-SAM conversion of coproporphyrinogen III to protoporphyrinogen IX.

Summary: hemN binds S-adenosyl-L-methionine at the unique iron of its radical SAM [4Fe-4S] cluster and cleaves it to the 5'-deoxyadenosyl radical; two SAM are consumed per protoporphyrinogen IX formed.

Reason: Not in GOA. Added under the RADICAL_SAM treatment rule, which treats GO:1904047 as a core cosubstrate-binding function of every radical SAM enzyme whose catalysis is established. This is a molecular function the protein itself performs, so the participation test is met directly: hemN binds SAM and cleaves it, rather than merely being required for a process that consumes it. UniProt's curated cofactor note records the exchangeable S-adenosyl-L-methionine on the radical SAM cluster and the entry's binding features name the 4Fe-4S-S-AdoMet ligand, so the claim rests on curated record content rather than on an electronic GO line. Coded IC because the inference is the reviewer's, drawn from that curated content and the established coproporphyrinogen dehydrogenase activity rather than from a SAM-binding assay on this protein. Comparator check, against GOA rather than against this project's own proposals: GOA does annotate GO:1904047 to radical SAM enzymes in exactly this role, by UniRule -- ECOLI/queE (UR000100349), ECOLI/moaA and PSEPK/moaA (UR000101305), METEA/pqqE and PSEPK/pqqE (UR000098303). So the absence here is patchy UniRule coverage, which rules happen to carry the term, not a GO convention against annotating a radical SAM enzyme's own cosubstrate. That is also why those five genes have an existing row to ACCEPT or MODIFY while this one needs a NEW row.