LOXL2

LOXL2
Identifiers
Aliases	LOXL2 , LOR2, WS9-14, lysyl oxidase like 2, LOR
External IDs	OMIM: 606663 MGI: 2137913 HomoloGene: 1742 GeneCards: LOXL2
Gene location (Human) Chr. Chromosome 8 (human) [1] Band 8p21.3 Start 23,296,897 bp [1] End 23,425,328 bp [1]
Gene location (Mouse) Chr. Chromosome 14 (mouse) [2] Band 14|14 D2 Start 69,846,517 bp [2] End 69,933,283 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium tibia adipose tissue smooth muscle tissue periodontal fiber placenta subcutaneous adipose tissue abdominal fat sural nerve appendix Top expressed in calvaria body of femur ankle joint ankle external carotid artery cumulus cell dermis internal carotid artery belly cord yolk sac 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 human 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 [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Lysyl oxidase homolog 2 is an enzyme that in humans is encoded by the LOXL2 gene. ^{[5] [6]}

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. ^[6]

LOXL2 can also crosslink collagen type IV and hence influence the sprouting of new blood vessels. ^[7]

Clinical significance

LOXL2 is an enzyme that is up-regulated in several types of cancer and is associated with a poorer prognosis. ^{[8] [9]} LOXL2 changes the structure of histones (proteins that are attached to DNA) ^[10] and thus changes the shape of the cells, making it easier for the cancer cells to metastasize. ^[11]

An antibody that inhibits the activity of LOXL2, simtuzumab and is currently in clinical trials for the treatment of several types of cancer and fibrotic diseases such as liver fibrosis. ^[12]

See also

• LOXL1
• LOXL3
• LOXL4

References

1. GRCh38: Ensembl release 89: ENSG00000134013 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034205 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Jourdan-Le Saux C, Le Saux O, Donlon T, Boyd CD, Csiszar K (July 1998). "The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2-p21.3". Genomics. 51 (2): 305–7. doi:10.1006/geno.1998.5356. PMID   9722957.
6. "Entrez Gene: LOXL2 lysyl oxidase-like 2".
7. Bignon M, Pichol-Thievend C, Hardouin J, Malbouyres M, Bréchot N, Nasciutti L, Barret A, Teillon J, Guillon E, Etienne E, Caron M, Joubert-Caron R, Monnot C, Ruggiero F, Muller L, Germain S (2011). "Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane". Blood. 118 (14): 3979–89. doi: 10.1182/blood-2010-10-313296 . PMID   21835952. S2CID   16622717.
8. Nishioka T, Eustace A, West C (2012). "Lysyl oxidase: from basic science to future cancer treatment". Cell Struct. Funct. 37 (1): 75–80. doi: 10.1247/csf.11015 . PMID   22453058.
9. Cano A, Santamaría PG, Moreno-Bueno G (2012). "LOXL2 in epithelial cell plasticity and tumor progression". Future Oncol. 8 (9): 1095–108. doi:10.2217/fon.12.105. PMID   23030485.
10. Herranz N, Dave N, Millanes-Romero A, Morey L, Díaz VM, Lórenz-Fonfría V, Gutierrez-Gallego R, Jerónimo C, Di Croce L, García de Herreros A, Peiró S (2012). "Lysyl oxidase-like 2 deaminates lysine 4 in histone H3". Molecular Cell. 46 (3): 369–376. doi: 10.1016/j.molcel.2012.03.002 . hdl: 10230/25392 . PMID   22483618.
11. Moreno-Bueno G, Salvador F, Martín A, Floristán A, Cuevas EP, Santos V, Montes A, Morales S, Castilla MA, Rojo-Sebastián A, Martínez A, Hardisson D, Csiszar K, Portillo F, Peinado H, Palacios J, Cano A (2011). "Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas". EMBO Mol Med. 3 (9): 528–544. doi:10.1002/emmm.201100156. PMC   3377095 . PMID   21732535.
12. "Search of: simtuzumab - List Results". ClinicalTrials.gov. Retrieved 25 February 2015.

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, Fogelgren B, Szauter KM, Mink M, Csiszar K (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): 220–4. 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): 171–4. 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): 8157–60. 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): 149–56. 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): 12939–44. 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, Kessler O, Cohen T, Resnick M, Neeman M, Neufeld G (April 2003). "Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo". Cancer Research. 63 (7): 1657–66. 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): 1565–73. PMID   12820424.
• Vadasz Z, Kessler O, Akiri G, Gengrinovitch S, Kagan HM, Baruch Y, Izhak OB, Neufeld G (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, Nieto MA, Cano A, Portillo F (October 2005). "A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression". The EMBO Journal. 24 (19): 3446–58. doi:10.1038/sj.emboj.7600781. PMC   1276164 . PMID   16096638.
• Akagawa H, Narita A, Yamada H, Tajima A, Krischek B, Kasuya H, Hori T, Kubota M, Saeki N, Hata A, Mizutani T, Inoue I (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): 377–87. doi:10.1007/s00439-007-0333-3. PMID   17287949. S2CID   25771968.