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LOXL2

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LOXL2
Identifiers
AliasesLOXL2, LOR2, WS9-14, lysyl oxidase like 2, LOR
External IDsOMIM: 606663; MGI: 2137913; HomoloGene: 1742; GeneCards: LOXL2; OMA:LOXL2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002318

NM_033325

RefSeq (protein)

NP_002309

NP_201582

Location (UCSC)Chr 8: 23.3 – 23.43 MbChr 14: 69.85 – 69.93 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function

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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

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

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000134013Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034205Ensembl, 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. ^ a b "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. (Retracted, see doi:10.1016/j.molcel.2016.06.013, PMID 27392148,  Retraction Watch. If this is an intentional citation to a retracted paper, please replace {{retracted|...}} with {{retracted|...|intentional=yes}}.)
  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.
[edit]
  • Overview of all the structural information available in the PDB for UniProt: Q9Y4K0 (Lysyl oxidase homolog 2) at the PDBe-KB.

Further reading

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