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MGP001833

UniProt Annotations

Entry Information
Gene Namelysyl oxidase-like 2
Protein EntryLOXL2_HUMAN
UniProt IDQ9Y4K0
SpeciesHuman
Comments
Comment typeDescription
Biophysicochemical PropertiesKinetic parameters: KM=1.01 mM for 1,5-diaminopentane {ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596}; KM=1.05 mM for spermine {ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596}; KM=0.59 uM for tropoelastin (without the first three SRCR domains) {ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596}; KM=0.62 uM for tropoelastin (without all four SRCR domains) {ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596}; Note=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).;
Catalytic ActivityPeptidyl-L-lysyl-peptide + O(2) + H(2)O = peptidyl-allysyl-peptide + NH(3) + H(2)O(2). {ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596}.
CofactorName=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000250};
CofactorName=lysine tyrosylquinone residue; Xref=ChEBI:CHEBI:20489; Evidence={ECO:0000250}; Note=Contains 1 lysine tyrosylquinone. {ECO:0000250};
DomainThe fourth SRCR domain plays a important role in optimizing the catalytic activity of the lysyl-oxidase like (LOX) catalytic domain.
Enzyme RegulationAccording to some reports, it is inhibited by beta-aminopropionitrile (BAPN) (PubMed:20439985 and PubMed:23319596). According to another report, it is not inhibited by beta-aminopropionitrile (BAPN) (PubMed:20306300). Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner. {ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:20818376, ECO:0000269|PubMed:23319596}.
FunctionMediates 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. {ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20026874, ECO:0000269|PubMed:21233336, ECO:0000269|PubMed:21732535, ECO:0000269|PubMed:21835952, ECO:0000269|PubMed:22483618}.
InductionStrongly induced in hypoxia. Direct transcriptional target of HIF1A. {ECO:0000269|PubMed:20026874}.
MiscellaneousIts 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 (PubMed:21732535). Allosteric inhibition by AB0023 inhibits formation of the tumor microenvironment and reduces metastatic tumor burden in xenograft models (PubMed:20818376 and PubMed:21732535). 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 (PubMed:22157764). {ECO:0000305|PubMed:21732535, ECO:0000305|PubMed:22157764}.
PtmN-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. {ECO:0000269|PubMed:23319596}.
PtmThe 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.
Sequence CautionSequence=AAD34343.1; Type=Erroneous termination; Positions=775; Note=Translated as stop.; Evidence={ECO:0000305};
SimilarityBelongs to the lysyl oxidase family. {ECO:0000305}.
SimilarityContains 4 SRCR domains. {ECO:0000255|PROSITE- ProRule:PRU00196}.
Subcellular LocationSecreted, extracellular space, extracellular matrix, basement membrane {ECO:0000250}. 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.
SubunitComponent of some chromatin repressor complex. Interacts with SNAI1. {ECO:0000269|PubMed:16096638}.
Tissue SpecificityExpressed in many tissues. Highest expression in reproductive tissues, placenta, uterus and prostate. Up- regulated in a number of cancers cells and tissues.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/LOXL2ID41192ch8p21.html";
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