Lysyl oxidase homolog 4 (LOXL4)

Lysyl oxidase homolog 4 (LOXL4) is a secreted copper-dependent amine oxidase encoded by the LOXL4 gene on chromosome 10q24.2, consisting of 17 exons and producing a 756-amino-acid protein with a molecular mass of 84.5 kDa, including a 24-residue signal peptide. It features four N-terminal scavenger receptor cysteine-rich (SRCR) domains and a C-terminal LOX domain with copper-binding sites, lysine tyrosylquinone (LTQ) cofactor (formed by Lys638 and Tyr693), and cytokine receptor-like (CRL) domain, enabling catalytic activity for oxidative deamination of lysine and hydroxylysine residues in collagen and elastin, generating covalent cross-links, hydrogen peroxide, and peptidyl aldehydes to stabilize the extracellular matrix (ECM). LOXL4 is expressed at low levels in normal tissues like skeletal muscle, pancreas, and testes, and localizes to cytoplasm, ECM, and nucleus; it undergoes alternative splicing (e.g., splv-1 lacking exon 9, splv-2 lacking exons 8-9) in serosal cavity tumors, shifting from tumor suppressor to oncogenic function. In cancer, it exhibits bidirectional roles: up-regulated (oncogenic, promoting proliferation, migration, invasion, metastasis via FAK/Src, H2O2-mediated adhesion, exosome transfer inducing PD-L1 in macrophages) in gastric, breast (e.g., TNBC), ovarian, head and neck squamous cell, esophageal, and colorectal cancers; down-regulated (tumor suppressor via methylation, inhibiting growth) in bladder and lung cancers; conflicting reports in hepatocellular carcinoma. Potential biomarker for prognosis, diagnosis, and therapeutic targeting in tumors.

Other names

Lysyl oxidase-like 4Lysyl oxidase-like protein 4LOXC