LOX Gene (Lysyl Oxidase): Function, Mutations, and Disease Links | Biomedical Reference

The LOX gene encodes lysyl oxidase, a copper-dependent amine oxidase that catalyzes the crosslinking of collagen and elastin in the extracellular matrix (ECM). This enzymatic activity is critical for the structural integrity and tensile strength of connective tissues. LOX is synthesized as a 50 kDa proenzyme (pro-LOX) and secreted into the ECM, where it is proteolytically cleaved by bone morphogenetic protein 1 (BMP1) into a functional 32 kDa enzyme and an 18 kDa propeptide (LOX-PP). The active enzyme initiates the formation of covalent crosslinks by oxidizing peptidyl lysine and hydroxylysine residues in collagen, and lysine residues in elastin, to peptidyl alpha-aminoadipic-delta-semialdehyde (allysine). Beyond its structural role, LOX and its propeptide have been implicated in various cellular processes, including cell motility, gene regulation, and tumor suppression or promotion, depending on the cellular context. Dysregulation of LOX expression and activity is associated with fibrotic diseases, cardiovascular disorders, and cancer progression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Collagen biosynthesis and modifying enzymes

• Elastin synthesis

• Extracellular matrix organization

• Integrin signaling pathway

• Hypoxia-inducible factor (HIF) signaling

• TGF-beta signaling pathway

• Focal adhesion pathway

Lysyl oxidase (LOX) is a 417-amino acid, copper-dependent amine oxidase. It is synthesized as a preproprotein with a signal peptide, a propeptide region (LOX-PP), and a conserved catalytic domain at the C-terminus. The catalytic domain contains the copper-binding site, the lysyl tyrosyl quinone (LTQ) cofactor, and the cytokine receptor-like (CRL) domain. The propeptide is cleaved extracellularly by BMP1 to yield the active enzyme. The active LOX enzyme deaminates lysine and hydroxylysine residues in collagen and elastin, producing allysine, which spontaneously reacts to form crosslinks. LOX-PP, the released propeptide, has its own biological activities, including tumor suppressor functions and regulation of cell differentiation. LOX is secreted and localizes to the ECM, where it plays a structural role. It is also found intracellularly, where it can influence gene transcription. The protein is highly conserved across species.