Mitochondrial lipoyl synthase that inserts sulfur atoms into octanoylated lipoyl domains during endogenous protein lipoylation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0009107 lipoate biosynthetic process | IBA GO_REF:0000033 | MODIFY | Summary: Lipoate biosynthetic process described the core process for LIP1, but GO:0009107 was obsoleted (2026-08-22) in favor of protein lipoylation. Reason: LIP1 catalyzes the sulfur-insertion step of endogenous protein lipoylation; GO:0009107 is now obsolete (replaced_by GO:0009249 protein lipoylation, per GO, obsoleted because term usage was inconsistent), so the annotation should move to the replacement term. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:1934604 · mouse lipoyl synthase Lias SUPPORTS TRANSFER PANTHER:PTN000101947 SUPPORTS TRANSFER Propagation of the lipoate-synthesis role is sound; the MODIFY is ontology maintenance only, because GO:0009107 was obsoleted (2026-08-22) with replaced_by GO:0009249 protein lipoylation. Proposed replacements: protein lipoylation Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes file:POPTR/LIP1/LIP1-uniprot.txt PATHWAY: Protein modification; protein lipoylation via endogenous pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein]: step 2/2. |
| GO:0016992 lipoate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Lipoate synthase activity is the specific molecular function of LIP1. Reason: The reviewed entry identifies LIP1 as lipoate synthase EC 2.8.1.8. Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic catalytic activity is correct but too broad for a characterized lipoate synthase. Reason: Use the specific lipoate synthase activity term. Proposed replacements: lipoate synthase activity Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrion is the supported localization for LIP1. Reason: The reviewed entry places LIP1 in mitochondria. Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0009107 lipoate biosynthetic process | IEA GO_REF:0000120 | MODIFY | Summary: Lipoate biosynthetic process described the core process for LIP1, but GO:0009107 was obsoleted (2026-08-22) in favor of protein lipoylation. Reason: LIP1 catalyzes the sulfur-insertion step of endogenous protein lipoylation; GO:0009107 is now obsolete (replaced_by GO:0009249 protein lipoylation, per GO, obsoleted because term usage was inconsistent), so the annotation should move to the replacement term. Proposed replacements: protein lipoylation Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes file:POPTR/LIP1/LIP1-uniprot.txt PATHWAY: Protein modification; protein lipoylation via endogenous pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein]: step 2/2. |
| GO:0009249 protein lipoylation | IEA GO_REF:0000104 | ACCEPT | Summary: Protein lipoylation is an appropriate process for LIP1. Reason: The pathway annotation describes endogenous protein lipoylation via lipoyl-lysine formation. Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt PATHWAY: Protein modification; protein lipoylation via endogenous pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein]: step 2/2. |
| GO:0016783 sulfurtransferase activity | IEA GO_REF:0000104 | MODIFY | Summary: Sulfurtransferase activity is a broad description of the lipoate synthase reaction. Reason: Use the specific lipoate synthase activity term for this radical SAM enzyme. Proposed replacements: lipoate synthase activity Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes |
| GO:0016992 lipoate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Lipoate synthase activity is the specific molecular function of LIP1. Reason: The reviewed entry identifies LIP1 as lipoate synthase EC 2.8.1.8. Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes |
| GO:0051536 iron-sulfur cluster binding | IEA GO_REF:0000002 | MODIFY | Summary: Iron-sulfur cluster binding is correct but less specific than the 4Fe-4S cluster annotation. Reason: The reviewed entry specifies two 4Fe-4S clusters per subunit. Proposed replacements: 4 iron, 4 sulfur cluster binding Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Binds 2 [4Fe-4S] clusters per subunit. |
| GO:0051539 4 iron, 4 sulfur cluster binding | IEA GO_REF:0000120 | ACCEPT | Summary: 4 iron, 4 sulfur cluster binding is a supported cofactor feature of LIP1. Reason: The reviewed entry states that LIP1 binds two 4Fe-4S clusters per subunit. Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Binds 2 [4Fe-4S] clusters per subunit. |
| GO:1904047 S-adenosyl-L-methionine binding | IC file:POPTR/LIP1/LIP1-uniprot.txt | NEW | Summary: LIP1 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 lipoyl group 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: LIP1 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 lipoate synthase 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. Supporting Evidence: file:POPTR/LIP1/LIP1-uniprot.txt Note=Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated file:POPTR/LIP1/LIP1-uniprot.txt cysteines and an exchangeable S-adenosyl-L-methionine file:POPTR/LIP1/LIP1-uniprot.txt /ligand_note="4Fe-4S-S-AdoMet" |
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Download this section (compressed HTML)Q: Which mitochondrial lipoate-dependent enzyme complexes are most sensitive to LIP1 perturbation in Populus?
Experiment: Quantify lipoylated mitochondrial enzyme subunits and lipoate-dependent dehydrogenase activities in LIP1 knockdown or mutant tissue.
Type: targeted functional assay
LIP1-uniprot.txt and LIP1-goa.tsv.Loading supporting content…
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