LOXL2 Recombinant Protein

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. [provided by RefSeq, Jul 2008]

Function: Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine). When secreted in extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding. When nuclear, acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation. Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E-cadherin, probably by mediating deamination of histone H3. Also involved in E-cadherin repression following hypoxia, a hallmark of epithelial to mesenchymal transition believed to amplify tumor aggressiveness, suggesting that it may play a role in tumor progression. Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation. Ref.7 Ref.8 Ref.11 Ref.12 Ref.13 Ref.16

Catalytic activity: Peptidyl-L-lysyl-peptide + O2 + H2O = peptidyl-allysyl-peptide + NH3 + H2O2. Ref.9 Ref.14 Ref.17

Cofactor: Copper

By similarity.Contains 1 lysine tyrosylquinone

By similarity.

Enzyme regulation: According to some reports, it is inhibited by beta-aminopropionitrile (BAPN) (Ref.9 and Ref.17). According to another report, it is not inhibited by beta-aminopropionitrile (BAPN) (Ref.14). Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner. Ref.9 Ref.10 Ref.14 Ref.17

Subunit structure: Component of some chromatin repressor complex. Interacts with SNAI1. Ref.7

Subcellular location: Secreted › extracellular space › extracellular matrix › basement membrane

By similarity. Nucleus. Chromosome. Note: Associated with chromatin. It is unclear how LOXL2 is nuclear: it contains a clear signal sequence and is predicted to localize in the extracellular medium. However, different reports confirmed the intracellular location and its key role in transcription regulation. Ref.7 Ref.16 Ref.17

Tissue specificity: Expressed in many tissues. Highest expression in reproductive tissues, placenta, uterus and prostate. Up-regulated in a number of cancers cells and tissues.

Induction: Strongly induced in hypoxia. Direct transcriptional target of HIF1A. Ref.8 Ref.9 Ref.10 Ref.14 Ref.17

Domain: The fourth SRCR domain plays a important role in optimizing the catalytic activity of the lysyl-oxidase like (LOX) catalytic domain.

Post-translational modification: The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.N-glycosylated. N-glycosylation on Asn-455 and Asn-644 may be essential for proper folding and secretion; may be composed of a fucosylated carbohydrates attached to a trimannose N-linked glycan core. Ref.17

Miscellaneous: Its overexpression in a number of cancer and its ability to promote epithelial to mesenchymal transition suggest that LOXL2 might play a role in tumor progression: expression is correlated with metastasis and decreased survival in patients with aggressive breast cancer (Ref.13). Allosteric inhibition by AB0023 inhibits formation of the tumor microenvironment and reduces metastatic tumor burden in xenograft models (Ref.10 and Ref.13). However, inhibiting the enzyme activity of LOXL2 may not be sufficient, since mutants that lack enzyme activity or inhibition of the activity by AB0023 antibody does not prevent inhibition of the differentiation of keratinocytes, thereby promoting development of squamous cell carcinomas (Ref.15).

Sequence similarities: Belongs to the lysyl oxidase family.Contains 4 SRCR domains.

Biophysicochemical propertiesKinetic parameters:kcat is 2.04 min(-1) with tropoelastin as substrate (without the first three SRCR domains). kcat is 0.62 min(-1) with tropoelastin as substrate (without all four SRCR domains).KM=1.01 mM for 1,5-diaminopentane Ref.9 Ref.17KM=1.05 mM for spermineKM=0.59 µM for tropoelastin (without the first three SRCR domains)KM=0.62 µM for tropoelastin (without all four SRCR domains)

Sequence caution: The sequence AAD34343.1 differs from that shown. Reason: Erroneous termination at position 775. Translated as stop.