======= LOXL2 ======= == Gene Information == * **Official Symbol**: LOXL2 * **Official Name**: lysyl oxidase like 2 * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4017|4017]] * **UniProt**: [[https://www.uniprot.org/uniprot/Q9Y4K0|Q9Y4K0]] * **Interactions**: [[https://thebiogrid.org/search.php?search=LOXL2&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20LOXL2|Open PubMed]] * **OMIM**: [[https://omim.org/entry/606663|Open OMIM]] == Function Summary == * **Entrez Summary**: N/A * **UniProt Summary**: 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}. |SRCR| |Lysyl oxidase| |protein-lysine 6-oxidase activity| |peptidyl-lysine oxidation| |negative regulation of stem cell population maintenance| |oligosaccharide binding| |protein oxidation| |heterochromatin organization| |positive regulation of chondrocyte differentiation| |endothelial cell proliferation| |regulation of stem cell population maintenance| |positive regulation of cartilage development| |response to copper ion| |collagen fibril organization| |positive regulation of epithelial to mesenchymal transition| |scavenger receptor activity| |regulation of chondrocyte differentiation| |copper ion binding| |sprouting angiogenesis| |endothelial cell migration| |regulation of cartilage development| |epithelial to mesenchymal transition| |electron transfer activity| |epithelial cell migration| |regulation of epithelial to mesenchymal transition| |epithelium migration| |epithelial cell proliferation| |basement membrane| |tissue migration| |chromatin| |mesenchymal cell differentiation| |ameboidal-type cell migration| |electron transport chain| |mesenchyme development| |aging| |peptidyl-lysine modification| |angiogenesis| |extracellular matrix organization| |response to hypoxia| |response to decreased oxygen levels| |collagen-containing extracellular matrix| |response to metal ion| |response to oxygen levels| |extracellular structure organization| |blood vessel morphogenesis| |generation of precursor metabolites and energy| |supramolecular fiber organization| |blood vessel development| |vasculature development| |cardiovascular system development| |response to inorganic substance| |cell population proliferation| |endocytosis| |tube morphogenesis| |import into cell| |chromatin organization| |calcium ion binding| |tube development| |negative regulation of transcription by RNA polymerase II| |circulatory system development| |peptidyl-amino acid modification| |anatomical structure formation involved in morphogenesis| |cell adhesion| |biological adhesion| |negative regulation of developmental process| |oxidation-reduction process| |cell migration| |positive regulation of cell differentiation| |endoplasmic reticulum| |chromosome organization| |cell motility| |localization of cell| |response to abiotic stimulus| |negative regulation of transcription, DNA-templated| |negative regulation of multicellular organismal process| |negative regulation of nucleic acid-templated transcription| |negative regulation of RNA biosynthetic process| |locomotion| |negative regulation of RNA metabolic process| |positive regulation of developmental process| |negative regulation of cellular macromolecule biosynthetic process| |negative regulation of nucleobase-containing compound metabolic process| |negative regulation of macromolecule biosynthetic process| |negative regulation of cellular biosynthetic process| |negative regulation of biosynthetic process| |movement of cell or subcellular component| |extracellular space| |negative regulation of gene expression| |positive regulation of multicellular organismal process| |tissue development| |regulation of cell differentiation| |protein-containing complex subunit organization| |vesicle-mediated transport| |membrane| \\ === CRISPR Data === ^Screen^Score^ |[[:results:exp7|Bortezomib 0.05μM R00 exp7]]|-1.75| |[[:results:exp23|Nocodazole 0.02μM R00 exp23]]|-1.72| No correlation found to any other genes in chemogenomics. Global Fraction of Cell Lines Where Essential: 0/726 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/28| |bone|0/25| |breast|0/33| |central nervous system|0/56| |cervix|0/4| |colorectal|0/17| |esophagus|0/13| |fibroblast|0/1| |gastric|0/15| |kidney|0/21| |liver|0/20| |lung|0/75| |lymphocyte|0/14| |ovary|0/26| |pancreas|0/24| |peripheral nervous system|0/16| |plasma cell|0/15| |prostate|0/1| |skin|0/24| |soft tissue|0/7| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/29| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 10053 * **Expression level (log2 read counts)**: 1.83 {{:chemogenomics:nalm6 dist.png?nolink |}}