Molecular identification of hydroxylysine kinase and of ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and phosphoethanolamine
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PHYKPL/AGXT2L2 catalyzes PLP-dependent breakdown of 5-phosphohydroxy-L-lysine to ammonia, inorganic phosphate, and 2-aminoadipate semialdehyde, functioning downstream of AGPHD1/HYKK in a two-step hydroxylysine catabolism route.
"The phosphorylation product made by this enzyme was metabolized by AGXT2L2, which converted it to ammonia, inorganic phosphate, and 2-aminoadipate semialdehyde."
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Despite homology to class-III aminotransferases, AGXT2L2 does not catalyze transamination but instead acts as an ammoniophospholyase.
"Unlike AGXT2, AGXT2L1 and AGXT2L2 did not act as transaminases"
Mutations in the AGXT2L2 gene cause phosphohydroxylysinuria
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Compound heterozygous mutations (p.Gly240Arg, p.Glu437Val) in AGXT2L2/PHYKPL cause phosphohydroxylysinuria; mutant recombinant proteins are largely insoluble, indicating loss of phosphohydroxylysine phospholyase activity in vivo. The condition does not appear to be a neurometabolic disease based on patient phenotype diversity.
"We conclude that phosphohydroxylysinuria is due to mutations in the AGXT2L2 gene and the resulting lack of activity of phosphohydroxylysine phospholyase in vivo."
Gene Ontology annotation through association of InterPro records with GO terms.
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Electronic Gene Ontology annotations created by ARBA machine learning models
Towards a proteome-scale map of the human protein-protein interaction network.
Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
A proteome-scale map of the human interactome network.
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Reactome pathway (cached file not available)
Deep research on PHYKPL function
Falcon deep research synthesis on PHYKPL/AGXT2L2 function, kinetics, and pathway placement
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PHYKPL acts as a PLP-dependent ammoniophospholyase downstream of AGPHD1/HYKK in hydroxylysine catabolism, with strong primary-biochemistry evidence anchored in Veiga-da-Cunha 2012.
"PHYKPL (synonym **AGXT2L2**) encodes a **pyridoxal-5′-phosphate (PLP)-dependent ammoniophospholyase** whose primary, experimentally demonstrated function is to catalyze elimination of **5-phosphohydroxy-L-lysine (5PHyl)** to yield **2-aminoadipate semialdehyde (2-AASA)**, **inorganic phosphate (Pi)**, and **ammonia (NH3)**."
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Recombinant human PHYKPL/AGXT2L2 shows Km of 16.9 ± 4.5 μM and Vmax of 256 ± 15 nmol/min/mg for 5PHyl, with substrate inhibition above ~100 μM and inhibition by inorganic phosphate.
"Kinetic parameters reported for recombinant human AGXT2L2 acting on 5PHyl include: - **Km(5PHyl) = 16.9 ± 4.5 μM** - **Vmax = 256 ± 15 nmol·min⁻¹·mg⁻¹ protein**"
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Localization was originally reported as cytosolic based on TargetP/Psort II predictions in the 2012 paper, but UniProt subsequently curated PHYKPL as mitochondrial; falcon noted this is a prediction rather than direct microscopy/proteomics evidence.
"AGXT2L2 (PHYKPL) is described as a **cytosolic enzyme**, consistent with **TargetP** and **Psort II** predictions cited in the biochemical characterization paper."