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
Gene location (Human)
Chr.	Chromosome 8 (human)
End	23,425,328 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	69,933,283 bp
RNA expression pattern
	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
	; ; ; ;
	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
	4017
	94352
	ENSG00000134013
	ENSMUSG00000034205
	Q9Y4K0
	P58022
	NM_002318
	NM_033325
	NP_002309
	NP_201582
	Wikidata
View/Edit Human	View/Edit Mouse

Lysyl oxidase homolog 2 is an enzyme that in humans is encoded by the LOXL2 gene.⁵⁶

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.⁸⁹ 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, is currently in clinical trials for the treatment of several types of cancer and fibrotic diseases such as liver fibrosis.¹²

References

GRCh38: Ensembl release 89: ENSG00000134013 – Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000034205 – Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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): 305–307. doi:10.1006/geno.1998.5356. PMID 9722957.
"Entrez Gene: LOXL2 lysyl oxidase-like 2".
Bignon M, Pichol-Thievend C, Hardouin J, Malbouyres M, Bréchot N, Nasciutti L, et al. (2011). "Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane". Blood. 118 (14): 3979–3989. doi:10.1182/blood-2010-10-313296. PMID 21835952. S2CID 16622717.
Nishioka T, Eustace A, West C (2012). "Lysyl oxidase: from basic science to future cancer treatment". Cell Structure and Function. 37 (1): 75–80. doi:10.1247/csf.11015. PMID 22453058.
Cano A, Santamaría PG, Moreno-Bueno G (2012). "LOXL2 in epithelial cell plasticity and tumor progression". Future Oncology. 8 (9). London, England: 1095–1108. doi:10.2217/fon.12.105. PMID 23030485.
Cebrià-Costa JP, Pascual-Reguant L, Gonzalez-Perez A, Serra-Bardenys G, Querol J, Cosín M, et al. (January 2020). "LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells". Oncogene. 39 (1): 79–121. doi:10.1038/s41388-019-0969-1. hdl:10230/44004. PMC 6937214. PMID 31462706.
Moreno-Bueno G, Salvador F, Martín A, Floristán A, Cuevas EP, Santos V, et al. (2011). "Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas". EMBO Molecular Medicine. 3 (9): 528–544. doi:10.1002/emmm.201100156. PMC 3377095. PMID 21732535.
"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, 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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000134013 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[Jourdan-Le_1998-5] 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): 305–307. doi:10.1006/geno.1998.5356. PMID 9722957.

[entrez-6] "Entrez Gene: LOXL2 lysyl oxidase-like 2".

[7] Bignon M, Pichol-Thievend C, Hardouin J, Malbouyres M, Bréchot N, Nasciutti L, et al. (2011). "Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane". Blood. 118 (14): 3979–3989. doi:10.1182/blood-2010-10-313296. PMID 21835952. S2CID 16622717.

[Nishioka_2012-8] Nishioka T, Eustace A, West C (2012). "Lysyl oxidase: from basic science to future cancer treatment". Cell Structure and Function. 37 (1): 75–80. doi:10.1247/csf.11015. PMID 22453058.

[Cano_2012-9] Cano A, Santamaría PG, Moreno-Bueno G (2012). "LOXL2 in epithelial cell plasticity and tumor progression". Future Oncology. 8 (9). London, England: 1095–1108. doi:10.2217/fon.12.105. PMID 23030485.

[10] Cebrià-Costa JP, Pascual-Reguant L, Gonzalez-Perez A, Serra-Bardenys G, Querol J, Cosín M, et al. (January 2020). "LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells". Oncogene. 39 (1): 79–121. doi:10.1038/s41388-019-0969-1. hdl:10230/44004. PMC 6937214. PMID 31462706.

[11] Moreno-Bueno G, Salvador F, Martín A, Floristán A, Cuevas EP, Santos V, et al. (2011). "Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas". EMBO Molecular Medicine. 3 (9): 528–544. doi:10.1002/emmm.201100156. PMC 3377095. PMID 21732535.

[urlSearch_of:_simtuzumab_-_List_Results_-_ClinicalTrials.gov-12] "Search of: simtuzumab - List Results". ClinicalTrials.gov. Retrieved 25 February 2015.

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Function

Clinical significance

See also

References

External links

Further reading