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lysyl oxidase

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Target id: 3097

Nomenclature: lysyl oxidase

Family: 1.4.3.13 Lysyl oxidases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 417 5q23.1 LOX lysyl oxidase
Mouse - 411 18 28.22 cM Lox lysyl oxidase
Rat - 411 18q11 Lox lysyl oxidase
Gene and Protein Information Comments
Alternative splicing of the human gene results in multiple transcript variants, the longest of which encodes the preproprotein that is post-translationally processed to generate a regulatory propeptide and the mature enzyme.
Previous and Unofficial Names Click here for help
protein-lysine 6-oxidase
Database Links Click here for help
Alphafold P28300 (Hs), P28301 (Mm)
BRENDA 1.4.3.13
ChEMBL Target CHEMBL2249 (Hs), CHEMBL4523209 (Mm)
Ensembl Gene ENSG00000113083 (Hs), ENSMUSG00000024529 (Mm), ENSRNOG00000014426 (Rn)
Entrez Gene 4015 (Hs), 16948 (Mm), 24914 (Rn)
Human Protein Atlas ENSG00000113083 (Hs)
KEGG Enzyme 1.4.3.13
KEGG Gene hsa:4015 (Hs), mmu:16948 (Mm), rno:24914 (Rn)
OMIM 153455 (Hs)
Pharos P28300 (Hs)
RefSeq Nucleotide NM_002317 (Hs), NM_010728 (Mm), 148747377 (Mm), NM_017061 (Rn)
RefSeq Protein NP_002308 (Hs), NP_034858 (Mm), NP_058757 (Rn)
UniProtKB P28300 (Hs), P28301 (Mm)
Wikipedia LOX (Hs)
Enzyme Reaction Click here for help
EC Number: 1.4.3.13 H2O + L-lysyl-[protein] + O2 = [protein]-(S)-2-amino-6-oxohexanoate + H2O2 + NH4+

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CCT365623 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 3
⤷ pIC50 6.1 (IC50 9x10-7 M) [3]
compound 21b [PMID: 31430136] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 pIC50 4
⤷ pIC50 5.5 (IC50 3.3x10-6 M) [4]
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cytokine production & signalling
Immuno Process:  Immune system development
Gene Expression and Pathophysiology Comments
Mutations in the LOX gene are associated with a predisposition to thoracic aortic aneurysms and dissections [1]. Experimental evidence shows that mutant LOX proteins do not transit to the Golgi, do not have copper incorporated, and hence the proteins do not become catalytically active [2]. So, the LOX loss-of-function is due to a secretion defect rather than to a gross protein structural deformity.

References

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1. Guo DC, Regalado ES, Gong L, Duan X, Santos-Cortez RL, Arnaud P, Ren Z, Cai B, Hostetler EM, Moran R et al.. (2016) LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections. Circ Res, 118 (6): 928-34. [PMID:26838787]

2. Lee VS, Halabi CM, Broekelmann TJ, Trackman PC, Stitziel NO, Mecham RP. (2019) Intracellular retention of mutant lysyl oxidase leads to aortic dilation in response to increased hemodynamic stress. JCI Insight, 5. DOI: 10.1172/jci.insight.127748 [PMID:31211696]

3. Leung L, Niculescu-Duvaz D, Smithen D, Lopes F, Callens C, McLeary R, Saturno G, Davies L, Aljarah M, Brown M et al.. (2019) Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships. J Med Chem, 62 (12): 5863-5884. [PMID:31070916]

4. Smithen DA, Leung LMH, Challinor M, Lawrence R, Tang H, Niculescu-Duvaz D, Pearce SP, Mcleary R, Lopes F, Aljarah M et al.. (2020) 2-Aminomethylene-5-sulfonylthiazole Inhibitors of Lysyl Oxidase (LOX) and LOXL2 Show Significant Efficacy in Delaying Tumor Growth. J Med Chem, 63 (5): 2308-2324. [PMID:31430136]

How to cite this page

1.4.3.13 Lysyl oxidases: lysyl oxidase. Last modified on 11/09/2019. Accessed on 28/04/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3097.