LOXL2

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]

lysyl oxidase-like 2

Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine) (PubMed:27735137).
Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation (PubMed:27735137).
Shows no activity against histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27' (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated (H3K4me2) (PubMed:27735137).
Also mediates deamination of methylated TAF10, a member of the transcription factor IID (TFIID) complex, which induces release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription (PubMed:25959397).
LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and SOX2 (By similarity).
Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E-cadherin CDH1, probably by mediating deamination of histone H3 (PubMed:16096638, PubMed:27735137, PubMed:24414204).
During EMT, involved with SNAI1 in negatively regulating pericentromeric heterochromatin transcription (PubMed:24239292).
SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (PubMed:24239292).
Interacts with the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1 pathway of the unfolded protein response, leading to expression of several transcription factors involved in EMT and subsequent EMT induction (PubMed:28332555).
Involved in E-cadherin repression following hypoxia, a hallmark of EMT believed to amplify tumor aggressiveness, suggesting that it may play a role in tumor progression (PubMed:20026874).
When secreted into the extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:20306300).
Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding (PubMed:21835952).
Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation (By similarity).

AgingManual Assertion Based On ExperimentTAS:ProtInc
Cell adhesionManual Assertion Based On ExperimentTAS:ProtInc
Cellular protein modification processManual Assertion Based On ExperimentIDA:UniProtKB
Collagen fibril organizationManual Assertion Based On ExperimentIMP:UniProtKB
Endothelial cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Endothelial cell proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Epithelial to mesenchymal transitionManual Assertion Based On ExperimentIDA:UniProtKB
Heterochromatin organizationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of stem cell population maintenanceISS:UniProtKB
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-lysine oxidationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of chondrocyte differentiationISS:UniProtKB
Positive regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentIMP:UniProtKB
Response to copper ionManual Assertion Based On ExperimentIDA:UniProtKB
Response to hypoxiaISS:UniProtKB
Sprouting angiogenesisManual Assertion Based On ExperimentIMP:UniProtKB

Secreted, extracellular space, extracellular matrix, basement membrane
Nucleus
Chromosome
Endoplasmic reticulum
Associated with chromatin (PubMed:27735137).
It is unclear how LOXL2 is nuclear as it contains a signal sequence and has been shown to be secreted (PubMed:23319596).
However, a number of reports confirm its intracellular location and its key role in transcription regulation (PubMed:22204712, PubMed:22483618).

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.