SPAC16E8.17c

Summary: Generic InterPro-derived parent of the specific activity, which is already annotated.

Reason: True but uninformative: GO:0004775 succinate-CoA ligase (ADP-forming) activity, accepted in this review, entails it.

Summary: ADP-forming succinyl-CoA synthetase activity (PAINT/EC); ATP specificity is shown for the S. cerevisiae enzyme and inferred by descent for S. pombe.

Reason: Family membership (HAMAP MF_03222, NCBIfam TIGR01019) supports the ADP-forming succinate-CoA ligase reaction; the alpha subunit binds CoA and phosphate and carries the phosphohistidine intermediate, so it contributes to the heterodimer activity. Consistent with the PAINT node.

Summary: ADP-forming succinyl-CoA synthetase activity (PAINT/EC); ATP specificity is shown for the S. cerevisiae enzyme and inferred by descent for S. pombe.

Reason: Family membership (HAMAP MF_03222, NCBIfam TIGR01019) supports the ADP-forming succinate-CoA ligase reaction; the alpha subunit binds CoA and phosphate and carries the phosphohistidine intermediate.

Summary: PAINT inference of GDP-forming activity at an alpha-subunit node shared by ADP- and GDP-forming enzymes; the S. pombe enzyme is predicted to be the ADP-forming type (single A-type beta subunit; not assayed).

Reason: The alpha subunit does not set nucleotide specificity: by family rule (HAMAP MF_03222) it binds CoA and phosphate while nucleotide specificity is provided by the beta subunit, and the PomBase TCA-cycle GO-CAM (gomodel:665912ed00000015) models both S. pombe subunits with succinate-CoA ligase (ADP-forming) activity. That is a curator's choice of term resting on the PAINT annotation, not an assay. The PTN000122012 node sits on the alpha subunit, which in animals partners both ATP- and GTP-specific beta subunits, so the GDP-forming label rides down to alpha subunits whose only partner is an A-type beta subunit (S. pombe has a single beta subunit, SPCC1620.08). Changed from KEEP_AS_NON_CORE, because the review argues the activity does not apply to the S. pombe enzyme. Re-examined with the family trees (2026-11-11, revised 2026-11-12): SPCC1620.08 falls in the A-type (SUCLA2) lineage of the beta subunit with S. cerevisiae Lsc2, and S. pombe, like the other fungal genomes under the alpha-subunit node PTN000874203 in the PANTHER tree, has no G-type (SUCLG2) beta gene, so the term should stop at that node. The absence is not kingdom-wide: early-diverging fungi (Mortierellomycota, Basidiobolus, Rozella) keep a SUCLG2-type gene. Within Dikarya one Taphrinomycotina species, Saitoella complicata, also has a Gln20 SUCLG2-type entry (A0A0E9NQG5); it groups with the Mortierellomycota genes only weakly, so vertical retention, transfer and contamination are not distinguished and its origin is unresolved. S. pombe itself has one beta gene, of the A type, so this does not change the reading for S. pombe. The action stays short of REMOVE because the S. pombe enzyme has not been assayed and Pro at position 20 of a beta subunit does not exclude GTP use; the S. cerevisiae ortholog Lsc1, whose enzyme used ATP but not GTP when assayed, removes the same row.

Summary: ORFeome YFP screen: mitochondrion.

Summary: PAINT inference of mitochondrial location.

Reason: UniProt places the protein in the mitochondrion on the HAMAP rule MF_03222 together with the S. pombe ORFeome localization (ECO:0000269, PMID:16823372), and it has a predicted mitochondrial transit peptide (1-22). The organelle claim holds.

Summary: UniProt/ARBA location mapping; consistent.

Reason: UniProt places the protein in the mitochondrion on the HAMAP rule MF_03222 together with the S. pombe ORFeome localization (ECO:0000269, PMID:16823372), and it has a predicted mitochondrial transit peptide (1-22).

Summary: Matrix location of this TCA enzyme (inference or mapping); consistent.

Reason: UniProt places the protein in the mitochondrion on the HAMAP rule MF_03222 together with the S. pombe ORFeome localization (ECO:0000269, PMID:16823372), and it has a predicted mitochondrial transit peptide (1-22). A soluble TCA-cycle enzyme without transmembrane segments, imported by a matrix-targeting presequence, acts in the matrix; this IC inference is the sub-compartment beside the root mitochondrion rows.

Summary: 13C tracing in S. pombe versus S. japonicus shows that S. pombe runs a respiratory, oxidative TCA cycle (curator, full text).

Summary: PAINT inference; TCA cycle step.

Reason: Family-rule FUNCTION and PATHWAY (HAMAP MF_03222): succinyl-CoA synthetase performs the substrate-level phosphorylation step of the TCA cycle; consistent with the PAINT node.

Summary: InterPro/UniPathway mapping; consistent.

Reason: Family-rule FUNCTION and PATHWAY (HAMAP MF_03222): succinyl-CoA synthetase performs the substrate-level phosphorylation step of the TCA cycle.

Summary: Succinyl-CoA metabolism; the direct process of the reaction the enzyme catalyses.

Reason: True by family rule (HAMAP MF_03222): the enzyme interconverts succinyl-CoA and succinate, the reaction is reversible, and the term names the direct process of the reaction. It is not an ancestor of the TCA cycle term, and the gene carries no more specific succinyl-CoA process term. Changed from KEEP_AS_NON_CORE so that the term has the same action on every reviewed subunit of the enzyme, including the S. cerevisiae ortholog Lsc1, the source of this ISS.

Summary: Subunit of the ADP-forming succinate-CoA ligase heterodimer.

Reason: Family-rule SUBUNIT (HAMAP MF_03222): heterodimer of an alpha and a beta subunit; this protein is the alpha subunit of the ADP-forming enzyme.