lysyl oxidase | 1.4.3.13 Lysyl oxidases | IUPHAR/BPS Guide to PHARMACOLOGY

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lysyl oxidase

Target not currently curated in GtoImmuPdb

Target id: 3097

Nomenclature: lysyl oxidase

Family: 1.4.3.13 Lysyl oxidases

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 417 5q23.1 LOX lysyl oxidase
Mouse - 411 18 D1; 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
protein-lysine 6-oxidase
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 1.4.3.13 H2O + L-lysyl-[protein] + O2 = [protein]-(S)-2-amino-6-oxohexanoate + H2O2 + NH4+

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CCT365623 Hs Inhibition 6.1 pIC50 3
pIC50 6.1 (IC50 9x10-7 M) [3]
compound 21b [PMID: 31430136] Hs Inhibition 5.5 pIC50 4
pIC50 5.5 (IC50 3.3x10-6 M) [4]
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0045652 regulation of megakaryocyte differentiation IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:1990869 cellular response to chemokine IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:1990869 cellular response to chemokine IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045652 regulation of megakaryocyte differentiation IEA
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 20/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3097.