| Aspect | Finding | Key evidence/source (paper and year) | Notes/limitations |
|---|---|---|---|
| Gene/protein identity | Human **PHYKPL / AGXT2L2** encodes **5-phosphohydroxy-L-lysine phospho-lyase**; a PLP-dependent enzyme matching UniProt Q8IUZ5 | Veiga-da-Cunha et al., *J Biol Chem* (2012) (pqac-00000004, pqac-00000005) | Identity is well matched to the UniProt entry; older literature often used the synonym **AGXT2L2** rather than **PHYKPL** |
| Enzymatic reaction | Catalyzes breakdown of **5-phosphohydroxy-L-lysine (5PHyl)** to **2-aminoadipate semialdehyde (2-AASA) + NH3 + Pi** | Veiga-da-Cunha et al. (2012) (pqac-00000001, pqac-00000004, pqac-00000005) | Experimentally demonstrated with recombinant human enzyme; this is the primary functional annotation |
| Cofactor / enzyme class | **Pyridoxal phosphate (PLP)-dependent** ammoniophospholyase within the class-III aminotransferase-fold family | Veiga-da-Cunha et al. (2012) (pqac-00000004, pqac-00000005) | Despite homology to aminotransferases, no aminotransferase activity was detected in the reported assays |
| Key kinetics | **Km = 16.9 ± 4.5 µM** for 5PHyl; **Vmax = 256 ± 15 nmol·min⁻¹·mg⁻¹** protein | Veiga-da-Cunha et al. (2012), Figure 4/text (pqac-00000001, pqac-00000012) | Saturation curve showed **substrate inhibition** above ~100 µM 5PHyl |
| Product / inhibitor behavior | Reaction yields stoichiometric **phosphate, ammonia, and 2-AASA**; **inorganic phosphate** inhibits activity, with ~50% reduction at the highest tested Pi (2–10 mM range tested) | Veiga-da-Cunha et al. (2012) (pqac-00000001) | Supports assignment as a phospho-lyase; inhibition data are biochemical, not in vivo physiology |
| Evidence type | Function established by **recombinant human protein expression, purification, and in vitro enzyme assays** measuring Pi, NH3, and 2-AASA formation | Veiga-da-Cunha et al. (2012) (pqac-00000005) | Strong primary-biochemistry evidence; human cellular knockout/knockdown studies remain limited in retrieved sources |
| Pathway context | Functions in **hydroxylysine catabolism** downstream of **AGPHD1/HYKK (5-hydroxy-L-lysine kinase)**, converting phosphorylated hydroxylysine to 2-AASA | Veiga-da-Cunha et al. (2012); Van Schaftingen et al. (2015) (pqac-00000003, pqac-00000004) | Pathway placement is well supported biochemically, but broader physiological flux regulation in humans is still sparsely characterized |
| Localization | Reported/predicted as **cytosolic** based on bioinformatic localization analyses | Veiga-da-Cunha et al. (2012) (pqac-00000001, pqac-00000003) | Retrieved evidence indicates prediction rather than extensive direct microscopy/proteomics confirmation |
| Disease / Mendelian link | Proposed disease gene for **phosphohydroxylysinuria**; authors expected AGXT2L2 defects to elevate urinary 5PHyl | Veiga-da-Cunha et al. (2012); Open Targets summary (pqac-00000001, pqac-00000008) | A 2013 JIMD mutation paper was identified in search results but not retrievable here; therefore this row relies on the 2012 primary paper plus database-level association evidence |
| Other disease associations | Open Targets lists additional associations with **ulcerative colitis, dental caries, glomerulonephritis,** and **primary thrombocytopenia** besides phosphohydroxylysinuria | Open Targets Platform query (accessed via tool context) (pqac-00000008) | These are mostly genetic-association/database links, not direct mechanistic validation specific to PHYKPL biology |
| Recent 2023–2024 mentions | 2024 literature mentions PHYKPL mainly as a **PLP-enzyme homolog** in comparative/heme-metabolism discussion rather than providing new direct functional data | Key et al., *Biomolecules* (2024) (pqac-00000009) | No major 2023–2024 primary studies with new biochemical or localization data for human PHYKPL were retrieved |
| Current annotation confidence | **High confidence** for core enzymatic function; **moderate-to-low confidence** for localization detail, tissue physiology, and broader disease relevance | Synthesis of primary biochemistry and database evidence (pqac-00000001, pqac-00000004, pqac-00000008, pqac-00000012) | Literature on this specific human protein remains limited compared with better-studied metabolic enzymes |


*Table: This table summarizes the core functional annotation of human PHYKPL/AGXT2L2, including its experimentally demonstrated phospho-lyase reaction, kinetic parameters, pathway placement, localization, and disease links. It is useful as a compact evidence map separating strong biochemical findings from more tentative disease-association data.*