Human Recombinant LOXL2 - Fc Tagged
Reference ID:KB-3925
Western Blot
Flow Cytometry
Gene of Interest
Gene Synonyms:LOXL2
Protein Names:Lysyl oxidase homolog 2 (EC (Lysyl oxidase-like protein 2) (Lysyl oxidase-related protein 2) (Lysyl oxidase-related protein WS9-14)
Accession Data
Organism:Homo sapiens (Human)
Mass (kDa):867.25
Length (aa):774
Proteomics (Proteome ID):UP000005640
Proteomics (Chromosome): Chromosome 8
Activity Regulation: According 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}.
Catalytic Activity: Reaction=H2O + L-lysyl-[protein] + O2 = [protein]-(S)-2-amino-6-oxohexanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:24544, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:12448, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:131803; EC=; Evidence={ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596, ECO:0000269|PubMed:29581294};
Cofactor:Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000269|PubMed:29581294}; ; Name=lysine tyrosylquinone residue; Xref=ChEBI:CHEBI:20489; Evidence={ECO:0000269|PubMed:29581294}; Note=Contains 1 lysine tyrosylquinone. {ECO:0000250|UniProtKB:P33072};
Function [CC]: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). {ECO:0000250|UniProtKB:P58022, ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20026874, ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:21835952, ECO:0000269|PubMed:24239292, ECO:0000269|PubMed:24414204, ECO:0000269|PubMed:25959397, ECO:0000269|PubMed:27735137}.
Kinetics:BIOPHYSICOCHEMICAL PROPERTIES: Kinetic 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).;
Metal Binding:METAL 549 549 Calcium. {ECO:0000305|PubMed:29581294}.; METAL 550 550 Calcium; via carbonyl oxygen. {ECO:0000305|PubMed:29581294}.; METAL 626 626 Copper. {ECO:0000305|PubMed:29581294}.; METAL 628 628 Copper. {ECO:0000305|PubMed:29581294}.; METAL 630 630 Copper. {ECO:0000305|PubMed:29581294}.; METAL 722 722 Calcium. {ECO:0000305|PubMed:29581294}.; METAL 724 724 Calcium; via carbonyl oxygen. {ECO:0000305|PubMed:29581294}.; METAL 727 727 Calcium. {ECO:0000305|PubMed:29581294}.; METAL 728 728 Calcium. {ECO:0000305|PubMed:29581294}.
Induction:Strongly induced in hypoxia. Direct transcriptional target of HIF1A. {ECO:0000269|PubMed:20026874}.
Tissue Specificity:Expressed in many tissues (PubMed:10212285). Highest expression in reproductive tissues, placenta, uterus and prostate (PubMed:10212285). In esophageal epithelium, expressed in the basal, prickle and granular cell layers (PubMed:22204712). Up-regulated in a number of cancers cells and tissues. {ECO:0000269|PubMed:10212285, ECO:0000269|PubMed:22204712}.
Chemical Profile | ChEBI:H2O2 [CHEBI:16240]; H2O [CHEBI:15377]; L-lysine residue [CHEBI:29969]; Cu cation [CHEBI:23378]; O2 [CHEBI:15379]; (S)-2-amino-6-oxohexanoate residue [CHEBI:131803]; lysine tyrosylquinone residue [CHEBI:20489]; NH4(+) [CHEBI:28938]
ChEBI (Catalytic Activity):H2O2 [CHEBI:16240]; H2O [CHEBI:15377]; L-lysine residue [CHEBI:29969]; O2 [CHEBI:15379]; (S)-2-amino-6-oxohexanoate residue [CHEBI:131803]; NH4(+) [CHEBI:28938]
ChEBI (Cofactor):Cu cation [CHEBI:23378]; lysine tyrosylquinone residue [CHEBI:20489]
Mutagenesis:MUTAGEN 455 455 N->Q: Inhibits secretion. {ECO:0000269|PubMed:23319596}.; MUTAGEN 626 628 HRH->ARA: Abolishes oxidase activity and oxidation of trimethylated 'Lys-4' of histone H3 but does not affect secretion, interaction with SNAI1, binding to the CDH1 promoter, repression of CDH1 transcription or ability to induce EMT. {ECO:0000269|PubMed:24414204, ECO:0000269|PubMed:27735137}.; MUTAGEN 626 626 H->A: Loss of enzyme activity. {ECO:0000269|PubMed:29581294}.; MUTAGEN 628 628 H->A: Loss of enzyme activity. {ECO:0000269|PubMed:29581294}.; MUTAGEN 630 630 H->A: Loss of enzyme activity. {ECO:0000269|PubMed:29581294}.; MUTAGEN 644 644 N->Q: Inhibits secretion. {ECO:0000269|PubMed:23319596}.; MUTAGEN 653 653 K->A: Loss of enzyme activity. {ECO:0000269|PubMed:29581294}.; MUTAGEN 689 689 Y->A: Loss of enzyme activity. {ECO:0000269|PubMed:29581294}.; MUTAGEN 689 689 Y->F: Does not affect ability to inhibit keratinocyte differentiation. {ECO:0000269|PubMed:22157764}.
Miscellaneous [CC]:Its overexpression in a number of cancers 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:21233336, PubMed:21732535). Allosteric inhibition by AB0023 inhibits formation of the tumor microenvironment and reduces metastatic tumor burden in xenograft models (PubMed:20818376, PubMed:21732535). However, inhibiting the enzyme activity of LOXL2 may not be sufficient, since inhibition of keratinocyte differentiation is not prevented in mutants that lack enzyme activity nor by inhibition of activity by the AB0023 antibody, thereby promoting development of squamous cell carcinomas (PubMed:22157764). {ECO:0000305|PubMed:20818376, ECO:0000305|PubMed:21233336, ECO:0000305|PubMed:21732535, ECO:0000305|PubMed:22157764}.
Reagent Data
Region:Gln 26 - Gln 774
Molecular Weight:111.6
Purification System:Chromatography
Formulation:Sterile-filtered colorless solution
Formulation Concentration:1 mg/ml
Buffer Volume:Standard
Buffer Solution:PBS
Endotoxin Level:< 1%
Aggregate Tested By:SDS-PAGE
Endotoxin Screened:< 0.1 ng/ug
Purity:> 98%
Determined: SDS-PAGE
Validated: RP-HPLC
Sample Handling
Stability:This bioreagent is stable at 4°C (short-term) and -70°C(long-term). After reconstitution, sample may be stored at 4°C for 2-7 days and below -18°C for future use.
Preparation:Reconstitute in sterile distilled H2O to no less than 100 ug/ml; dilute reconstituted stock further in other aqueous solutions if needed. Please review COA for lot-specific instructions. Final measurements should be determined by the end-user for optimal performance.