sel0 (SPAC20G4.05c) is the fission yeast member of the SELO family (Pfam PF02696; InterPro IPR003846; HAMAP MF_00692 YdiU_SelO), predicted to be a mitochondrial protein AMPylase (protein adenylyltransferase). SELO-family enzymes adopt a protein-kinase-like (pseudokinase) fold but bind ATP in a "flipped" orientation and transfer AMP, rather than a phosphate, to serine, threonine and tyrosine residues of target proteins (AMPylation/adenylylation). The protein carries an N-terminal mitochondrial transit peptide, a conserved ATP-binding site and a Mg(2+)-dependent catalytic centre. In characterised orthologs (bacterial YdiU, budding yeast, human SELO), the enzyme localises to mitochondria, AMPylates proteins involved in redox homeostasis and metabolism, and contributes to the cellular response to oxidative stress; mammalian SELO additionally AMPylates mitochondrial metabolic enzymes such as glutamate dehydrogenase and pyruvate dehydrogenase. The activity, substrates and physiological role of the S. pombe protein itself have not been experimentally determined and are inferred from these orthologs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0070733 AMPylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred SELO-family AMPylase (protein adenylyltransferase) activity. This is the core molecular function of the gene and is consistent with the Pfam SelO domain, conserved ATP-binding/Mg(2+) catalytic residues, and demonstrated activity of orthologs. Reason: AMPylase activity (GO:0070733; synonym protein adenylyltransferase activity) is the defining function of the SELO family, demonstrated for bacterial, budding-yeast and human orthologs and phylogenetically propagated to the fission-yeast protein. It matches the UniProt EC 2.7.7.- / Rhea:54288 assignment and the conserved active-site residues. Retain as the core function. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred mitochondrial localization, consistent with the N-terminal mitochondrial transit peptide and the conserved mitochondrial localization of SELO orthologs. Reason: SELO orthologs localise to mitochondria and the S. pombe protein carries a UniProt mitochondrial transit peptide. Mitochondrion is the core cellular location where the AMPylase acts. Supporting Evidence: PMID:30270044 SelO pseudokinases localize UniProt:O13890 SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (UniProt Subcellular Location keyword-mapping) annotation of mitochondrial localization; redundant with, and consistent with, the IBA and ISS mitochondrion annotations. Reason: Correct location, derived from the UniProt mitochondrial subcellular-location assignment. Consistent with the transit peptide and ortholog data. Supporting Evidence: UniProt:O13890 SUBCELLULAR LOCATION: Mitochondrion |
| GO:0070733 AMPylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Electronic (Rhea reaction mapping, RHEA:54288) annotation of AMPylase activity. Consistent with the SELO-family reaction (L-tyrosyl-[protein] + ATP = O-(5'-adenylyl)-L-tyrosyl-[protein] + diphosphate). Reason: The Rhea-mapped reaction matches the UniProt catalytic-activity annotation and the SELO-family AMPylation chemistry. Redundant with the IBA/ISS AMPylase annotations; retain as supporting evidence for the core function. Supporting Evidence: UniProt:O13890 Xref=Rhea:RHEA:54288 |
| GO:0070733 AMPylase activity | ISO PMID:30270044 Protein AMPylation by an Evolutionarily Conserved Pseudokina... | ACCEPT | Summary: AMPylase activity transferred by orthology (ISO) from a characterised SELO ortholog. The 2018 Sreelatha et al. paper is the primary demonstration of SELO-family AMPylation. Reason: Orthology-based transfer of the experimentally demonstrated SELO AMPylase activity is well justified given the conserved SelO domain and active site. Same core molecular function as the IBA/ISS/Rhea lines. Supporting Evidence: PMID:30270044 transfers AMP from |
| GO:0070733 AMPylase activity | ISO PMID:40849408 A repurposed AMP binding domain reveals mitochondrial protei... | ACCEPT | Summary: AMPylase activity transferred by orthology (ISO) from mammalian SELO, which AMPylates mitochondrial metabolic enzymes. Same core molecular function. Reason: The 2025 Gonzalez et al. study confirms mammalian mitochondrial SELO AMPylase activity and family conservation; orthology transfer to S. pombe sel0 is justified by the conserved SelO domain. Redundant with the other AMPylase lines. Supporting Evidence: PMID:40849408 SelO is conserved in E. coli and S. cerevisiae, where it catalyzes AMPylation to protect cells from oxidative damage and cell death |
| GO:0070733 AMPylase activity | ISO PMID:9700395 Education and research: where are we going? | ACCEPT | Summary: AMPylase-activity annotation whose cited reference (PMID:9700395) is a mis-attributed, unrelated 1998 veterinary editorial. The molecular function is correct for the gene, but this specific citation is spurious. Reason: The AMPylase-activity assignment is correct and strongly supported by the other evidence lines (IBA, ISS, Rhea, PMID:30270044). The reference on THIS ISO row, PMID:9700395 ("Education and research: where are we going?", Aust Vet J 1998), is a wrong-identifier citation with no relation to SelO/AMPylation and cannot itself support the annotation (flagged in reference_review as WRONG_IDENTIFIER). Per project policy the GOA source id is not rewritten; the annotation is accepted on the strength of the corroborating evidence and the citation problem is documented rather than used as grounds for removal. Supporting Evidence: PMID:30270044 transfers AMP from |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of mitochondrial localization from human SELO (UniProtKB:Q08968). Consistent with the transit peptide and other mitochondrion annotations. Reason: Correct location, transferred from the experimentally characterised human ortholog and supported by the N-terminal mitochondrial transit peptide. Supporting Evidence: UniProt:O13890 SUBCELLULAR LOCATION: Mitochondrion |
| GO:0070733 AMPylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of AMPylase activity from human SELO (UniProtKB:Q08968). Same core molecular function as the other AMPylase lines. Reason: Justified orthology-based transfer of the SELO AMPylase activity, consistent with the conserved SelO domain and active site. Core molecular function. |
| GO:0098869 cellular oxidant detoxification | IC GO_REF:0000111 | KEEP AS NON CORE | Summary: Curator-inferred (IC) biological process, built on the ISS AMPylase-activity annotation. In characterised orthologs SELO AMPylates redox-homeostasis proteins and is required for the oxidative-stress response, so an oxidant- detoxification role is a reasonable inference for the fission-yeast protein, though it has not been demonstrated in S. pombe. Reason: The oxidative-stress/redox role of SELO is well supported for orthologs (PMID:30270044: SELO AMPylates redox-homeostasis proteins and is necessary for the oxidative-stress response). For S. pombe sel0 this remains an inference (IC on top of ISS), with no fission-yeast phenotype reported. Retain as a plausible, non-core biological-process annotation rather than a demonstrated core function; the demonstrated/inferable core is the AMPylase activity and its mitochondrial location. Note also that in mammals the process is framed as metabolic regulation (PMID:40849408) as well as redox protection, so the exact pombe process is uncertain. Supporting Evidence: PMID:30270044 is necessary for the proper cellular response to oxidative |
| GO:0018117 protein adenylylation | ISS GO_REF:0000024 | NEW | Summary: The biological process directly enabled by the AMPylase activity: covalent addition of AMP to protein amino-acid side chains. Proposed as a NEW annotation to make explicit the process corresponding to the (inferred) molecular function; not currently in GOA for this gene. Reason: GO:0018117 (protein adenylylation) is the process counterpart of the SELO AMPylase activity (GO:0070733) and is directly entailed by it. Adding it makes the core function's process explicit. Inferred by sequence similarity to characterised SELO orthologs; like the MF, not yet demonstrated in S. pombe. Supporting Evidence: PMID:30270044 transfers AMP from |
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Download this section (compressed HTML)Q: Is recombinant S. pombe sel0 catalytically active as an AMPylase in vitro, and does it self-AMPylate as seen for other SELO-family members?
Q: What are the endogenous AMPylation substrates of sel0 in fission-yeast mitochondria, and do they overlap with the redox and metabolic substrates seen in other species?
Q: Does a sel0 deletion sensitise S. pombe to oxidative stress or alter mitochondrial/respiratory metabolism?
Experiment: In vitro AMPylation assay of purified recombinant sel0 (with [alpha-32P]ATP or an N6-modified ATP analog) against candidate substrates and generic substrates, with active-site mutants as controls, to test catalytic competence.
Experiment: AMPylation-enrichment proteomics (hinT- or antibody-based) on mitochondria from wild-type versus sel0-deletion S. pombe to identify endogenous substrates.
Experiment: Phenotypic characterisation of a sel0-deletion strain under oxidative stress (H2O2, diamide, paraquat) and respiratory-growth conditions, with complementation by wild-type and catalytically dead sel0.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: Whether sel0 (SPAC20G4.05c) actually possesses AMPylase (protein adenylyltransferase) activity has not been tested in S. pombe; the activity is inferred entirely from orthologs. No in vitro assay or in vivo AMPylation readout has been reported for the fission-yeast protein.
OPEN BIOLOGY MF_DARK
What is known: SELO-family AMPylase activity is experimentally established for bacterial (E. coli YdiU), S. cerevisiae and human SELO, and the S. pombe protein retains the SelO domain (Pfam PF02696), the ATP-binding site and the Mg(2+)-coordinating catalytic residues, so catalytic competence is plausible but unproven.
Significance: Confirms whether sel0 is a bona fide enzyme in fission yeast or a catalytically compromised family member, and validates the propagated GO AMPylase annotation.
What would resolve it: In vitro AMPylation assay of recombinant sel0 with [alpha-32P]ATP or an ATP analog on candidate substrates, and detection of protein AMPylation in a S. pombe sel0-deletion vs wild-type background.
Provenance (the field's own admissions):
Gap: The in vivo substrate(s) of sel0 in S. pombe are unknown. It is undetermined which fission-yeast proteins (e.g. redox enzymes such as glutaredoxins, or mitochondrial metabolic enzymes) are AMPylated by sel0.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: In orthologs, SELO AMPylates proteins involved in redox homeostasis (PMID:30270044) and mammalian SELO AMPylates mitochondrial metabolic enzymes including glutamate dehydrogenase and pyruvate dehydrogenase (PMID:40849408), but the S. pombe substrate repertoire has not been mapped.
Significance: Identifying pombe substrates would define whether sel0 acts primarily in redox homeostasis, mitochondrial metabolic regulation, or another process.
What would resolve it: AMPylation-enrichment proteomics (e.g. hinT- or antibody-based) comparing wild-type and sel0-deletion S. pombe mitochondria.
Provenance (the field's own admissions):
Gap: It is unknown whether sel0 functions in oxidant detoxification / the oxidative- stress response in S. pombe. The GO cellular oxidant detoxification annotation is a curator inference from orthologs, not a fission-yeast phenotype.
OPEN BIOLOGY BP_DARK
What is known: SELO activity is necessary for the proper cellular response to oxidative stress in characterised orthologs (PMID:30270044) and protects E. coli and S. cerevisiae from oxidative damage (PMID:40849408); no oxidative-stress or other loss-of-function phenotype has been reported for a S. pombe sel0 deletion.
Significance: Establishes the physiological role of sel0 in fission yeast and whether the redox role of the family is conserved in this lineage.
What would resolve it: Phenotypic analysis of a S. pombe sel0-deletion strain under oxidative and other stresses (e.g. H2O2, diamide, respiratory-growth conditions).
Provenance (the field's own admissions):
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