cab4 (SPAC1F12.08) encodes a 316-residue protein that is the fission-yeast ortholog of budding-yeast Cab4 (YGR277C), the phosphopantetheine adenylyltransferase (PPAT) of coenzyme A biosynthesis. It consists only of a cytidylyltransferase-like (nucleotidyltransferase, Rossmann-fold) domain homologous to the PPAT region of animal bifunctional CoA synthase (COASY); it has no dephospho-CoA kinase domain, the final CoA-forming step being carried out by the separate CoaE-family protein cab5. Its predicted activity is the ATP-dependent adenylylation of 4'-phosphopantetheine to 3'-dephospho-CoA, step four of CoA synthesis from pantothenate. The S. pombe protein has not been characterised biochemically; its function is inferred from domain content and orthology to S. cerevisiae Cab4, which is essential and is complemented by E. coli coaD. A YFP fusion localises to the cytosol and nucleus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO 'catalytic activity' from IPR004821 (cytidylyltransferase-like domain), the only catalytic domain of this protein. True but uninformative; the domain corresponds to the PPAT region of COASY and the S. cerevisiae ortholog Cab4 is a PPAT. Reason: The specific activity of a CTP_transf_like-only Cab4-family protein is pantetheine-phosphate adenylyltransferase activity; GOA currently carries no PPAT annotation for S. pombe cab4 at all. Proposed replacements: pantetheine-phosphate adenylyltransferase activity Supporting Evidence: file:SCHPO/cab4/cab4-uniprot.txt IPR004821; Cyt_trans-like. file:SCHPO/cab4/cab4-uniprot.txt SIMILARITY: To yeast YGR277c. PMID:19266201 Null mutants could be complemented by their bacterial counterparts coaBC, coaD and coaE, respectively. |
| GO:0004140 dephospho-CoA kinase activity | IBA GO_REF:0000033 | REMOVE | Summary: IBA from PANTHER PTN000075336, a dephospho-CoA kinase node (donors E. coli CoaE, M. tuberculosis CoaE, mouse/human COASY, Arabidopsis DPCK). cab4 sits in the same PANTHER subfamily (PTHR10695:SF46) only because COASY fuses PPAT and DPCK domains; cab4 itself has a single cytidylyltransferase-like PPAT domain (Pfam PF01467) and no CoaE/DPCK domain (no IPR001977 or PF01121), so the inherited kinase activity cannot be performed by this protein. DPCK in S. pombe is provided by cab5. Same conclusion as the S. cerevisiae CAB4 review. Reason: Domain architecture excludes dephospho-CoA kinase activity; the IBA is a family-level over-propagation from bifunctional COASY/CoaE donors to a PPAT-only member. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: UniProtKB:P0A6I9 · E. coli CoaE (DPCK-only) SUPPORTS SOURCE BUT NOT TARGET UniProtKB:Q13057 · human COASY (PPAT + DPCK fusion) SUPPORTS SOURCE BUT NOT TARGET Supporting Evidence: file:SCHPO/cab4/cab4-uniprot.txt IPR004821; Cyt_trans-like. file:SCHPO/cab4/cab4-uniprot.txt PF01467; CTP_transf_like; 1. file:SCHPO/cab4/cab4-uniprot.txt CHAIN 1..316 |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: HDA from the Matsuyama et al. 2006 ORFeome YFP screen (nucleus as well as cytosol). Small soluble proteins often give nucleocytoplasmic signals; no nuclear role for a PPAT is known. Reason: High-throughput signal without a known nuclear function. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: HDA from the Matsuyama et al. 2006 ORFeome YFP screen (cytosol). Consistent with cytosolic CoA synthesis and with the budding-yeast Cab4 in the soluble CoA-synthesizing complex. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome |
| GO:0015937 coenzyme A biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000075336) for CoA biosynthesis; sources include S. cerevisiae CAB4 and CAB5. Although the DPCK MF from this node is wrong for cab4, involvement in CoA biosynthesis is correct: PPAT is the penultimate step. Supporting Evidence: file:SCHPO/cab4/cab4-uniprot.txt SIMILARITY: To yeast YGR277c. PMID:19266201 genes YIL083C, YKL088W, YGR277C and YDR106C responsible for late CoA biosynthesis turned out as essential |
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Download this section (compressed HTML)Q: Does S. pombe cab4 assemble with hal3, cab5 and the CoaB enzyme into a CoA-synthesizing complex like the budding-yeast CoA-SPC, given that the S. pombe PPCDC is a single fused protein rather than a Cab3-based heterotrimer?
Experiment: Assay recombinant cab4 for 4'-phosphopantetheine adenylyltransferase activity and test complementation of an S. cerevisiae cab4 null or E. coli coaD mutant; confirm absence of dephospho-CoA kinase activity.
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