LOX - dismech genes

Normal function · from ai-gene-review (P28300, commit 79fe13b38970) · AI-generated, not KB evidence

LOX is a secreted, copper- and lysine-tyrosylquinone-dependent protein-lysine 6-oxidase synthesized as a preproprotein. Extracellular proteolysis produces a mature C-terminal enzyme that oxidatively deaminates selected peptidyl lysine and hydroxylysine residues in collagen and elastin, generating aldehydes that initiate covalent cross-links and stabilize collagen fibrils and elastic fibers. Collagen targeting is regulated by precursor processing and tyrosine sulfation, while the propeptide participates in recruitment to tropoelastin before being released as the noncatalytic LOX propeptide (LOX-PP). Loss-of-function variants impair LOX activity and cause familial thoracic aortic aneurysm and dissection, consistent with an essential role in aortic-wall extracellular-matrix integrity.

After secretion and extracellular processing of proLOX, the mature C-terminal copper/LTQ enzyme oxidatively deaminates selected lysine and hydroxylysine side chains in collagen and elastin to allysine and hydroxyallysine. These aldehydes initiate covalent cross-link formation, thereby stabilizing collagen fibrils and elastic fibers. Substrate delivery is form- and processing-dependent: sulfated tyrosines retained in the long mature form promote collagen binding, whereas the propeptide can recruit proLOX to fibulin-4/tropoelastin assemblies before it is released. These targeting interactions are not treated as stable complex membership. The released LOX-PP is a distinct noncatalytic product, and reported tumor-cell or nuclear effects are not assigned to this extracellular catalytic activity. Human catalytic-domain variants with reduced enzyme activity predispose to thoracic aortic disease, supporting the physiological importance of this reaction for aortic-wall matrix integrity without making disease or blood-vessel morphogenesis a second molecular function.

molecular function: protein-lysine 6-oxidase activity · directly involved in: peptidyl-lysine oxidation; collagen fibril organization; elastic fiber assembly · locations: extracellular matrix

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Familial Thoracic Aortic Aneurysm and Aortic Dissection	causative germline	mechanism: Extracellular matrix structural failure subtype: LOX-related scoped to subtype: LOX-related
Keratoconus	susceptibility

Mechanism modules · computed from kb/

aortopathy_tgfbeta_dysregulation via Familial Thoracic Aortic Aneurysm and Aortic Dissection