Human Gene LOXL2 (ENST00000389131.8) from GENCODE V44
Description: Homo sapiens lysyl oxidase like 2 (LOXL2), mRNA. (from RefSeq NM_002318) RefSeq Summary (NM_002318): 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]. Gencode Transcript: ENST00000389131.8 Gencode Gene: ENSG00000134013.16 Transcript (Including UTRs) Position: hg38 chr8:23,296,897-23,404,120 Size: 107,224 Total Exon Count: 14 Strand: - Coding Region Position: hg38 chr8:23,298,043-23,368,351 Size: 70,309 Coding Exon Count: 13
ID:LOXL2_HUMAN DESCRIPTION: RecName: Full=Lysyl oxidase homolog 2; EC=1.4.3.13; AltName: Full=Lysyl oxidase-like protein 2; AltName: Full=Lysyl oxidase-related protein 2; AltName: Full=Lysyl oxidase-related protein WS9-14; Flags: Precursor; 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. CATALYTIC ACTIVITY: Peptidyl-L-lysyl-peptide + O(2) + H(2)O = peptidyl-allysyl-peptide + NH(3) + H(2)O(2). COFACTOR: Copper (By similarity). COFACTOR: Contains 1 lysine tyrosylquinone (By similarity). ENZYME REGULATION: According to some reports, it is inhibited by beta-aminopropionitrile (BAPN) (PubMed:20439985). 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. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.01 mM for 1,5-diaminopentane; KM=1.05 mM for spermine; SUBUNIT: Component of some chromatin repressor complex. Interacts with SNAI1. 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. 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. PTM: 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. 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 (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). SIMILARITY: Belongs to the lysyl oxidase family. SIMILARITY: Contains 4 SRCR domains. SEQUENCE CAUTION: Sequence=AAD34343.1; Type=Erroneous termination; Positions=775; Note=Translated as stop;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y4K0
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004720 protein-lysine 6-oxidase activity GO:0005044 scavenger receptor activity GO:0005507 copper ion binding GO:0005515 protein binding GO:0009055 electron carrier activity GO:0016491 oxidoreductase activity GO:0016641 oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor GO:0046872 metal ion binding GO:0070492 oligosaccharide binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001666 response to hypoxia GO:0001837 epithelial to mesenchymal transition GO:0001935 endothelial cell proliferation GO:0002040 sprouting angiogenesis GO:0006325 chromatin organization GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006464 cellular protein modification process GO:0006898 receptor-mediated endocytosis GO:0007155 cell adhesion GO:0007568 aging GO:0010718 positive regulation of epithelial to mesenchymal transition GO:0018057 peptidyl-lysine oxidation GO:0022900 electron transport chain GO:0030199 collagen fibril organization GO:0032332 positive regulation of chondrocyte differentiation GO:0043542 endothelial cell migration GO:0045892 negative regulation of transcription, DNA-templated GO:0046688 response to copper ion GO:0055114 oxidation-reduction process GO:0070828 heterochromatin organization GO:1902455 negative regulation of stem cell population maintenance