Rat Pnkd encodes a metallo-beta-lactamase-fold protein related to hydroxyacylglutathione hydrolase. The 369-residue B4F7D2 product retains the PNKD catalytic-domain fold but differs internally and at its C-terminus from the longer rat product. PNKD proteins have isoform-dependent localization and a neuronal role in regulating synaptic release; the physiological hydrolytic substrate and the function of this particular product are unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004416 hydroxyacylglutathione hydrolase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: The conserved PNKD fold is not sufficient for a physiological HAGH substrate assignment. Human PNKD-L has extremely weak lactoylglutathione hydrolysis and fails to rescue HAGH-null fly extracts. Thus the reaction is not absolutely absent in vitro, but using it as the functional annotation of this altered rat product overstates substrate and biological-role evidence. Supporting Evidence: PMID:21487022 PNKD-L has extremely low but consistent SLG hydrolysis activity PMID:21487022 introduction of a human PNKD-L transgene into the same null background shows no rescue of SLG metabolism file:rat/Pnkd/Pnkd-bioinformatics/RESULTS.md | Domain: Metallo-beta-lactamase | 168–330 | 163 / 163 | 163 | |
| GO:0051596 methylglyoxal catabolic process | IEA GO_REF:0000002 | UNDECIDED | Summary: The best direct paralog comparison argues against treating PNKD-L as the glyoxalase-II step of methylglyoxal detoxification: it fails HAGH complementation. However, the exact rat product has different internal and terminal sequence, and a contribution to redox or methylglyoxal responses through another mechanism is not resolved. It is not assigned this pathway as a core function. Supporting Evidence: PMID:21487022 introduction of a human PNKD-L transgene into the same null background shows no rescue of SLG metabolism file:rat/Pnkd/Pnkd-bioinformatics/RESULTS.md | Domain: Metallo-beta-lactamase | 168–330 | 163 / 163 | 163 | |
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Download this section (compressed HTML)Q: Does the 369-residue rat product retain a physiological thioesterase substrate or interact with synaptic release proteins, and where does the endogenous product localize?
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