Gene Ontology annotation through association of InterPro records with GO terms
Mutations in PNKD causing paroxysmal dyskinesia alters protein cleavage and stability.
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Human PNKD-L has weak measurable S-D-lactoylglutathione hydrolysis in vitro, rather than the robust HAGH activity; no complete absence of hydrolysis is claimed.
"PNKD-L has extremely low but consistent SLG hydrolysis activity"
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Human PNKD-L does not restore lactoylglutathione metabolism in HAGH-null flies, arguing against physiological equivalence to glyoxalase II.
"introduction of a human PNKD-L transgene into the same null background shows no rescue of SLG metabolism"
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Tagged and untagged human PNKD-L in neuronal-derived cells support membrane association; this finding does not resolve localization of the altered rat B4F7D2 product.
"the results suggest that PNKD-L is a membrane-associated protein."
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The physiological PNKD-L substrate is proposed to be an unknown alpha-hydroxythioester.
"Sequence alignment and enzyme kinetics suggest that PNKD-L substrate may be an (as yet, unknown) α-hydroxythioester"
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Overexpressed PNKD-L did not co-localize with mitochondria in Cos7 cells, contradicting the mitochondrial localization reported by Ghezzi et al.
"When overexpressed, both PNKD-L–FLAG and PNKD-L–GFP fusion proteins show strong cellular membrane-localization patterns in Cos7 cells, and no co-localization with mitochondria was found"
Reproducible comparison of two rat Pnkd products
Pnkd B4F7D2 re-review: mapping onto reviewed human and mouse PNKD isoforms
Frozen exact-input ProtNLM output and UniProt sequence for B4F7D2
Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis.
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Defined neuronal PNKD constructs and mouse knockout experiments support a synaptic-release regulatory role; this does not demonstrate that the alternative B4F7D2 rat product has the same activity.
"PNKD interacts with synaptic active zone proteins Rab3-interacting molecule (RIM)1 and RIM2, localizes to synapses, and modulates neurotransmitter release."
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Endogenous Pnkd-L was immunoprecipitated with an antibody against a C-terminal peptide, a region that differs in B4F7D2.
"we immunoprecipiated Pnkd-L from C57BL/6 mouse frontal cortex homogenates using an antibody raised against a C-terminal peptide"
Paroxysmal non-kinesigenic dyskinesia is caused by mutations of the MR-1 mitochondrial targeting sequence.
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Human MR-1L and MR-1S were reported as mitochondrial proteins imported via an N-terminal targeting sequence that B4F7D2 shares; contradicted for PNKD-L by PMID:21487022.
"both MR-1L and MR-1S isoforms are mitochondrial proteins, imported into the organelle thanks to a 39 amino acid-long, N-terminal"
The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway.
Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia.
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Mouse PNKD is neuronal, one isoform is membrane-associated, and disease-mutant knock-in mice show striatal dopamine-release deficits (an organismal phenotype, not used for process annotation).
"One PNKD isoform is a membrane-associated protein."