LOXL2

Last updated
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
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 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]

Contents

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

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000134013 Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. Cebrià-Costa, J. P.; Pascual-Reguant, L.; Gonzalez-Perez, A.; Serra-Bardenys, G.; Querol, J.; Cosín, M.; Verde, G.; Cigliano, R. A.; Sanseverino, W.; Segura-Bayona, S.; Iturbide, A.; Andreu, D.; Nuciforo, P.; Bernado-Morales, C.; Rodilla, V.; Arribas, J.; Yelamos, J.; de Herreros, A. Garcia; Stracker, T. H.; Peiró, S. (2 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.
  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.

Further reading