LOXL3
Description
The LOXL3 (lysyl oxidase like 3) is a protein-coding gene located on chromosome 2.
Lysyl oxidase homolog 3 is an enzyme that in humans is encoded by the LOXL3 gene. This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Alternatively spliced transcript variants of this gene have been reported but their full-length nature has not been determined.
== Clinical significance == An autosomal recessive mutation (missense variant) in the LOXL3 gene is one of the causes of Stickler syndrome, a disease where collagen is not crosslinked properly. Common features are high myopia and cleft palate due to arthropathy (joint pathology) and vitreoretinopathy (pathology of the eye).
LOXL3 is a protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins. It catalyzes the post-translational oxidative deamination of peptidyl lysine residues in precursors of elastin and different types of collagens, a prerequisite in the formation of cross-links between collagens and elastin. LOXL3 is required for somite boundary formation by catalyzing oxidation of fibronectin (FN1), enhancing integrin signaling in myofibers and their adhesion to the myotendinous junction (MTJ). It acts as a regulator of inflammatory response by inhibiting differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg). LOXL3 interacts with STAT3 in the nucleus and catalyzes both deacetylation and oxidation of lysine residues on STAT3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity. Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated. LOXL3 is also able to catalyze deacetylation of lysine residues on STAT3.
LOXL3 is also known as LOXL, MYP28.
