LOXL2

LOXL2
Identifiers
Aliases	LOXL2, LOR2, WS9-14, lysyl oxidase like 2, LOR
External IDs	OMIM: 606663; MGI: 2137913; HomoloGene: 1742; GeneCards: LOXL2; OMA:LOXL2 - orthologs
Enzyme activity EC # BRENDA ExPASy KEGG MetaCyc 1.4.3.13 ↗ ↗ ↗ ↗
Gene location (Human) Chr. Chromosome 8 (human) Band 8p21.3 Start 23,296,897 bp End 23,425,328 bp
Gene location (Mouse) Chr. Chromosome 14 (mouse) Band 14|14 D2 Start 69,846,517 bp End 69,933,283 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium cartilage tissue tibia gonad adipose tissue smooth muscle tissue muscle layer of sigmoid colon periodontal fiber placenta subcutaneous adipose tissue Top expressed in calvaria body of femur ankle joint epithelium of lens ankle stroma of bone marrow migratory enteric neural crest cell external carotid artery cumulus cell dermis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor scavenger receptor activity oligosaccharide binding protein-lysine 6-oxidase activity oxidoreductase activity electron transfer activity protein binding copper ion binding metal ion binding calcium ion binding Cellular component nucleoplasm membrane chromosome extracellular region basement membrane extracellular matrix extracellular space chromatin nucleus endoplasmic reticulum collagen-containing extracellular matrix Biological process positive regulation of chondrocyte differentiation response to hypoxia collagen fibril organization epithelial to mesenchymal transition regulation of transcription, DNA-templated endothelial cell migration endothelial cell proliferation receptor-mediated endocytosis response to copper ion cell adhesion ageing negative regulation of transcription, DNA-templated sprouting angiogenesis transcription, DNA-templated electron transport chain negative regulation of transcription by RNA polymerase II positive regulation of epithelial to mesenchymal transition peptidyl-lysine oxidation heterochromatin organization negative regulation of stem cell population maintenance chromatin organization vesicle-mediated transport endocytosis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4017 94352 Ensembl ENSG00000134013 ENSMUSG00000034205 UniProt Q9Y4K0 P58022 RefSeq (mRNA) NM_002318 NM_033325 RefSeq (protein) NP_002309 NP_201582 Location (UCSC) Chr 8: 23.3 – 23.43 Mb Chr 14: 69.85 – 69.93 Mb PubMed search
Wikidata
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Lysyl oxidase homolog 2 is an enzyme that in humans is encoded by the LOXL2 gene.

Function

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.

LOXL2 can also crosslink collagen type IV and hence influence the sprouting of new blood vessels.

Clinical significance

LOXL2 is an enzyme that is up-regulated in several types of cancer and is associated with a poorer prognosis. LOXL2 changes the structure of histones (proteins that are attached to DNA) and thus changes the shape of the cells, making it easier for the cancer cells to metastasize.

An antibody that inhibits the activity of LOXL2, simtuzumab, is currently in clinical trials for the treatment of several types of cancer and fibrotic diseases such as liver fibrosis.

See also

• LOXL1
• LOXL3
• LOXL4

External links

• Overview of all the structural information available in the PDB for UniProt: Q9Y4K0 (Lysyl oxidase homolog 2) at the PDBe-KB.

Further reading

• Csiszar K (2001). Lysyl oxidases: a novel multifunctional amine oxidase family. Progress in Nucleic Acid Research and Molecular Biology. Vol. 70. pp. 1–32. doi:10.1016/S0079-6603(01)70012-8. ISBN 978-0-12-540070-1. PMID 11642359.
• Molnar J, Fong KS, He QP, Hayashi K, Kim Y, Fong SF, et al. (April 2003). "Structural and functional diversity of lysyl oxidase and the LOX-like proteins". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1647 (1–2): 220–224. doi:10.1016/s1570-9639(03)00053-0. PMID 12686136.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Saito H, Papaconstantinou J, Sato H, Goldstein S (March 1997). "Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence". The Journal of Biological Chemistry. 272 (13): 8157–8160. doi:10.1074/jbc.272.13.8157. PMID 9079631.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Jourdan-Le Saux C, Tronecker H, Bogic L, Bryant-Greenwood GD, Boyd CD, Csiszar K (April 1999). "The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues". The Journal of Biological Chemistry. 274 (18): 12939–12944. doi:10.1074/jbc.274.18.12939. PMID 10212285.
• Hein S, Yamamoto SY, Okazaki K, Jourdan-LeSaux C, Csiszar K, Bryant-Greenwood GD (January 2001). "Lysyl oxidases: expression in the fetal membranes and placenta". Placenta. 22 (1): 49–57. doi:10.1053/plac.2000.0580. PMID 11162352.
• Akiri G, Sabo E, Dafni H, Vadasz Z, Kartvelishvily Y, Gan N, et al. (April 2003). "Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo". Cancer Research. 63 (7): 1657–1666. PMID 12670920.
• Rost T, Pyritz V, Rathcke IO, Görögh T, Dünne AA, Werner JA (2003). "Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas". Anticancer Research. 23 (2B): 1565–1573. PMID 12820424.
• Vadasz Z, Kessler O, Akiri G, Gengrinovitch S, Kagan HM, Baruch Y, et al. (September 2005). "Abnormal deposition of collagen around hepatocytes in Wilson's disease is associated with hepatocyte specific expression of lysyl oxidase and lysyl oxidase like protein-2". Journal of Hepatology. 43 (3): 499–507. doi:10.1016/j.jhep.2005.02.052. PMID 16023247.
• Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, et al. (October 2005). "A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression". The EMBO Journal. 24 (19): 3446–3458. doi:10.1038/sj.emboj.7600781. PMC 1276164. PMID 16096638.
• Akagawa H, Narita A, Yamada H, Tajima A, Krischek B, Kasuya H, et al. (May 2007). "Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptibility gene to intracranial aneurysms". Human Genetics. 121 (3–4): 377–387. doi:10.1007/s00439-007-0333-3. PMID 17287949. S2CID 25771968.