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LOXL2 (lysyl oxidase-like 2)

Written2009-02Sheri FT Fong, Keith SK Fong, Katalin Csiszar
John A. Burns School of Medicine, University of Hawaii, 1960 East West Road, Biomed T415, Honolulu, HI 96822, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_nameslysyl oxidase-like 2
Alias_symbol (synonym)WS9-14
Other alias
HGNC (Hugo) LOXL2
LocusID (NCBI) 4017
Atlas_Id 41192
Location 8p21.3  [Link to chromosome band 8p21]
Location_base_pair Starts at 23296897 and ends at 23404209 bp from pter ( according to hg19-Feb_2009)  [Mapping LOXL2.png]
Local_order CHMP7 - R3HCC1 - LOXL2 - ENTPD4 - SLC25A37
Fusion genes
(updated 2016)
ENTPD4 (8p21.3) / LOXL2 (8p21.3)LOXL2 (8p21.3) / BCAP31 (Xq28)TUSC3 (8p22) / LOXL2 (8p21.3)
WARS2 (1p12) / LOXL2 (8p21.3)
Note Some databases also include LOR2 as an alias or synonym for LOXL2, but LOR2 actually refers to LOXL3.

DNA/RNA

 
  Figure 1. Lysyl oxidase-like 2 gene structure. Exons are depicted as boxes separated by intron sequences (solid lines). The size of each exon and intron is shown in base pairs, above and below the gene, respectively. The exons shaded in red encode amino acids sequences that are conserved in all lysyl oxidase family members. The exon shaded in blue contains the 3' UTR sequence.
Description The LOXL2 gene is located on chromosome 8p21.2-p21.3 (Jourdan-Le Saux et al., 1998). It is composed of fourteen exons and thirteen introns, distributed through approximately 107 kb of genomic DNA (Fong et al., 2007). Two transcripts of sizes 3.6 kb and 4.9 kb have been reported, with the smaller transcript much more abundant and resulting from three possible termination sites located 690 bp, 740 bp and 900 bp 3' of the termination codon (Jourdan-Le Saux et al., 1999). The termination site used for the larger 4.9 kb transcript has not been described. Intron 4 contains a polymorphic CA-repeat microsatellite (Fong et al., 2007) and there are at least 17 SNPs within the LOXL2 gene (Akagawa et al., 2007). The LOXL2 gene also contains a CpG island of approximately 1150 bp, starting 176 bases upstream of the transcriptional start and extending into intron 1 (Fong et al., 2007).
Transcription The LOXL2 promoter region contains numerous putative binding sites for transcription factors, including WT1, SP1, NF-kB and AP-1 (Fong et al., 2007).
LOXL2 gene expression is induced by TGF-b1 or indomethacin, and inhibited by retinoic acid or phorbol ester (Saito et al., 1997). It has also been described as a type II TGF-b receptor-dependent gene in lung adenocarcinoma subtypes (Borczuk et al., 2005). LOXL2 expression could be induced in MCF-7 breast cancer cells cultured on a collagen I matrix conditioned by fibroblasts (Kirschmann et al., 2002), in H292 human airway epithelial cells exposed to mite allergen (Vroling et al., 2007), and in MC3T3-E1 osteoblastic cells exposed to active vitamin D3 in culture (Nagaoka et al., 2008). LOXL2 is also induced by hypoxia. Hypoxia-inducible factor-1 alpha (HIF-1a) stimulates LOXL2 mRNA transcription in fibroblasts and renal tubular epithelial cells (Higgins et al., 2007; Salnikow et al., 2008). This upregulation was inhibited in fibroblasts by siRNA targeting the ETS1 transcription factor (Salnikow et al., 2008).
Transcription of the LOXL2 gene may also be affected by the methylation status of its CpG island (Fong et al., 2007).
Pseudogene No known pseudogene.

Protein

 
  Figure 2. Lysyl oxidase-like 2 protein structure. All members of the lysyl oxidase family of proteins share two highly conserved domains: a unique copper-binding (Cu) domain containing four histidines, shaded in red; and a cytokine-receptor like (CRL) domain similar to type I cytokine receptors, shaded in green. LOXL2, LOXL3 and LOXL4 also contain four Scavenger Receptor Cysteine-Rich (SRCR) domains, shaded in blue, that are commonly found in cell surface receptors and adhesion molecules. The predicted signal sequence is shaded in purple.
Description The LOXL2 transcript encodes for a 774-amino acid protein containing a predicted signal peptide of 22 amino acids, yielding an 87 kDa protein based on sequence analysis and produced by in vitro translation. In addition, there are three potential N-linked glycosylation sites (Saito et al., 1997). Western analysis of secreted proteins from LOXL2-transfected cells detected a protein of approximately 95 kDa, likely a glycosylated LOXL2 protein, and a protein of 63 kDa, which is an extracellular proteolytically processed form of LOXL2 (Akiri et al., 2003; Vadasz et al., 2005; Fong et al., 2007; Hollosi et al., 2009). Western analysis of cellular proteins isolated from LOXL2-transfected normal mammary epithelial cells revealed a 95 kDa protein similar to the secreted form and no processed form in the soluble cellular protein collection, with two additional LOXL2 proteins in the insoluble cellular protein collection: a 105 kDa protein that may be an alternately glycosylated full-length form, as well as a 50 kDa protein, which is another proteolytically processed form of LOXL2 (Hollosi et al., 2009). Although other LOX family members are processed extracellularly into their mature forms by bone morphogenetic protein-1 and related enzymes (Borel et al., 2001; Csiszar, 2001; Uzel et al., 2001), no potential processing site(s) or responsible enzymes have been identified for LOXL2.
Expression Tissue expression of LOXL2 mRNA has been described in extracts of spleen, thymus, prostate, testis, uterus, small intestine, colon, heart, brain, placenta, lung, liver, kidney, pancreas, skeletal muscle and bone (Jourdan-Le Saux et al., 1999; Pires Martins et al., 2001). LOXL2 was more highly expressed in fetal heart compared to adult heart, and was found in the left and right atrium and ventricles, and the apex of the adult heart, as well as the aorta (Pires Martins et al., 2001; Molnar et al., 2003).
As for normal cell types, LOXL2 mRNA expression has been reported in fibroblasts (Saito et al., 1997; Pires Martins et al., 2001; Kirschmann et al., 2002), melanocytes and B-cells (Pires Martins et al., 2001), syncytiotrophoblasts and cytotrophoblasts (Jourdan-Le Saux et al., 1999; Hein et al., 2001), bone marrow stromal cells (Monticone et al., 2004), and astrocytes from the optic nerve head (Urban et al., 2007). LOXL2 protein has been detected in syncytiotrophoblasts and cytotrophoblasts (Hein et al., 2001), bone marrow stromal cells (Monticone et al., 2004), colonic enteroendocrine cells and esophageal squamous cells (Fong et al., 2007), and mammary epithelial cells (Hollosi et al., 2009).
Localisation In cell culture, LOXL2 has been detected extracellularly (Akiri et al., 2003; Vadasz et al., 2005; Fong et al., 2007; Hollosi et al., 2009) and intracellularly (Fong et al., 2007; Hollosi et al., 2009), and also localized to the perinuclear compartment (Peinado et al., 2005). In tissues, LOXL2 has been localized to the cytoplasm in colonic enteroendocrine cells and esophageal squamous cells towards the lumen surface (Fong et al., 2007), and associated with the luminal membrane surface in mammary gland acini (Hollosi et al., 2009).
Function LOXL2, similar to its other LOX family members, has been reported to have amine oxidase activity, but unlike its family members, its enzyme activity was not inhibited by beta-aminoproprionitrile (BAPN) (Vadasz et al., 2005; Hollosi et al., 2009). Other LOX family members are known to oxidize peptidyl lysine and hydroxylysine residues in collagen and lysine residues in elastin to form the covalent cross-links that stabilize and insolubilize several fibrillar collagen types and elastin fibers (reviewed in Lucero and Kagan, 2006), and it has been reported that LOXL2 has catalytic activity against collagen type I (Vadasz et al., 2005). Treatment of MC3T3-E1 osteoblastic cells with active vitamin D3 resulted in increased LOXL2 expression (other LOX family members were not up-regulated), and increased collagen cross-links and acceleration of cross-link maturation (Nagaoka et al., 2008). As for its role in elastin fiber assembly, LOXL2 has been reported to interact with fibulin-5, which could tether LOXL2 onto microfibrils to facilitate elastic fiber assembly and maturation (Hirai et al., 2007). A single nucleotide polymorphism (SNP) in LOXL2 has been described to have an interactive effect with SNPs in the elastin/LIM kinase 1 locus in intracranial aneurysm susceptibility (Akagawa et al., 2007), and LOXL2 silencing repressed elastin gene transcription and eliminated elastic fiber formation by human umbilical vein endothelial cells (HUVEC) (Lelievre et al., 2008).
In diseases, LOXL2 has been reported to enhance the in vivo accumulation and deposition of collagen in breast tumors and glioma tumors formed by LOXL2-overexpressing cancer cells (Akiri et al., 2003). Increased LOXL2 has been described in hepatocytes from patients with Wilson's disease or primary biliary cirrhosis, which are fibrotic liver diseases (Vadasz et al., 2005); renal tubulointerstitial fibrosis from experimental unilateral ureteral obstruction and human renal samples of diabetic nephropathy, IgA nephropathy and hypertensive nephrosclerosis (Higgins et al., 2007); as well as a mouse model of chronic cholangitis which is similar to primary sclerosing cholangitis in humans (Nakken et al., 2007). Decreased LOXL2 mRNA expression was noted in human pelvic organ prolapse (Klutke et al., 2008).
LOXL2 is reduced in endothelial cells exposed to laminar shear stress, which induces reduction of atherogenicity (Chu and Peters, 2008). VE-statin/egfl7 that increases after arterial injury (Campagnolo et al., 2005), may modulate smooth muscle migration through interaction with the catalytic domain of LOXL2 and all LOX enzymes to inhibit enzyme activity (Lelievre et al., 2008). Increased LOXL2 has also been described in intracranial aneurysms, associated with a SNP in exon 5 (Akagawa et al., 2007).
LOXL2 is the only LOX family member not expressed in MC3T3-E1 osteoblastic cells (Atsawasuwan et al., 2005), and not up-regulated upon osteoblast differentiation (Kaku et al., 2007). Although expressed in bone marrow stromal cells (BMSC), LOXL2 was down-regulated in osteoblasts derived from BMSC (Qi et al., 2003; Monticone et al., 2004).
In addition, increased LOXL2 expression was observed in senescent fibroblasts, replicative senescence and stress-induced premature senescence (Saito et al., 1997; Pascal et al., 2005), and may be involved in primary open-angle glaucoma (Urban et al., 2007). LOXL2 also appears to have a role in cell proliferation (Akiri et al., 2003; Vadasz et al., 2005).
LOXL2 also has been described to have multiple roles in cancer, including epithelial-mesenchymal transition and the promotion of cancer cell adhesion, migration, invasion and metastases, and these are described in more detail in the following sections.
Homology In the human lysyl oxidase protein family, there are five members, named LOX, LOXL1, LOXL2, LOXL3 and LOXL4. They all contain a lysine tyrosylquinone (LTQ), the only mammalian cofactor derived from the cross-linking of two amino acid side chains (Anthony, 1996), and which is unique to the LOX family. The other highly conserved motif that is unique to the LOX family is the copper-binding domain, which contains four histidines (Krebs and Krawetz, 1993). All LOX family members also contain a cytokine receptor-like (CRL) domain, which has part of the consensus sequence of Class 1 cytokine receptors (Bazan, 1990). LOXL2 has closest homology to LOXL3 and LOXL4, as these three members differ from LOX and LOXL1 by the presence of 4 SRCR domains, and may represent a separate subfamily (Asuncion et al., 2001; Maki et al., 2001).

Mutations

Note Despite the implication of LOXL2 in several diseases and disorders, there are only sparse reports of any gene loss, polymorphisms or epigenetic alterations in the LOXL2 gene.
Epigenetics Increase in LOXL2 expression following treatment with the demethylating agent, 5-aza-2'-deoxycytidine, in colon and breast cancer cell lines indicate that the demethylation of the LOXL2 CpG island is a possible mechanism for regulating LOXL2 gene expression (Fong et al., 2007; Hollosi et al., 2009).
Somatic Loss of heterozygosity has been documented in colon and esophageal cancers at a level lower than the loss of heterozygosity documented in chromosome 8p21.2 - p21.3 for these cancers, indicating that LOXL2 is unlikely to be a tumor suppressor (Fong et al., 2007).

Implicated in

Note
  
Entity Blood cancers
Note LOXL2 mRNA was reported to be barely detectable or absent in the erythroleukemia cell line K562 and the T-cell leukemia cell line Jurkat (Saito et al., 1997).
  
  
Entity Brain cancer
Note LOXL2 mRNA was reported to be highly expressed in the cultured astrocytoma cell line U373MG (Saito et al., 1997).
C6-glioma cells, transfected with LOXL2, enhanced the in vivo accumulation and deposition of collagen in tumors (Akiri et al., 2003).
  
  
Entity Breast cancer
Note LOXL2 mRNA was demonstrated to be up-regulated in the invasive and metastatic cell lines, MDA-MB-231, Hs578T and MDA-MB435, compared to the poorly-invasive and non-metastatic cell lines, MCF-7 and T47D (Kirschmann et al., 2002; Akiri et al., 2003; Hollosi et al., 2009). MCF-7 cells, transfected with LOXL2, became more invasive in vivo and formed tumors with collagen deposition, and LOXL2 protein expression was more prevalent in poorly-differentiated compared to well-differentiated breast carcinomas (Akiri et al., 2003). LOXL2 mRNA was demonstrated to be present in 30 of 31 (97%) effusions due to breast cancer, compared to 17 of 23 (74%) primary breast carcinomas (Sebban et al., 2009). Increased LOXL2 protein expression was associated with decreased overall survival and decreased disease-free survival in patients with lymph node-negative breast adenocarcinomas (Peinado et al., 2008). LOXL2 mRNA expression may be regulated by methylation of its CpG island (Hollosi et al., 2009).
  
  
Entity Cervical cancer
Note LOXL2 mRNA was reported to be highly expressed in the adherent cultured cervical adenocarcinoma cell line HeLa, but not the non-adherent cultured cervical adenocarcinoma cell line HeLa-S3 (Saito et al., 1997).
  
  
Entity Colon cancer
Note LOXL2 was reported to be expressed in tumor-bearing tissue of the colon compared to absent expression in normal colon tissue using mining of the human EST database (Pires Martins et al., 2001). Increased LOXL2 mRNA expression has been shown in colon tumors (Fong et al., 2007; Macartney-Coxson et al., 2008). Increased LOXL2 protein expression is associated with less-differentiated colon cancers, which have more aggressive behavior and high incidence in metastasis (Fong et al., 2007), and has been shown in liver metastases due to colon cancer (Macartney-Coxson et al., 2008). LOXL2 mRNA expression may be regulated by methylation of its CpG island (Fong et al., 2007).
  
  
Entity Duodenal cancer
Note LOXL2 mRNA was reported to be highly expressed in the duodenal adenocarcinoma cell line HuTu80 (Saito et al., 1997).
  
  
Entity Epithelial-mesenchymal transition (EMT)
Note Increased LOXL2 mRNA expression was described in immortalized kidney epithelial cells that had undergone EMT (Kiemer et al., 2001). LOXL2 has been shown to interact with Snail through the SNAG domain with Snail's lysine residues 98 and 137 as possible substrates, leading to increased stability of Snail, down-regulation of E-cadherin, up-regulation of fibronectin and induction of EMT (Peinado et al., 2005). LOXL2 is thought to contribute to Snail stability by impeding GSK3b-dependent Snail degradation (Peinado et al., 2005). LOXL2 also interacts with fibulin-5 (Hirai et al., 2007), which has been implicated in EMT in mammary epithelial cells (Lee et al., 2008).
  
  
Entity Esophageal cancer
Note Increased LOXL2 mRNA expression has been reported in esophageal tumors (Fong et al., 2007).
  
  
Entity Fibrosarcoma
Note LOXL2 mRNA was reported to be highly expressed in the cultured fibrosarcoma cell line HT 1080 (Saito et al., 1997).
  
  
Entity Gastric cancer
Note LOXL2 mRNA was reported to be barely detectable or absent in the cultured gastric carcinoma cell line KATO III (Saito et al., 1997).
  
  
Entity Germ cell cancer
Note LOXL2 was reported to be expressed in tumor-bearing tissue of germ cells using mining of the human EST database (Pires Martins et al., 2001).
  
  
Entity Head and neck squamous cell carcinoma (HNSCC)
Note Reduced LOXL2 mRNA levels were noted in 9 of 10 HNSCC cell lines, but mean LOXL2 expression levels between malignantly transformed tissues and reference tissues were similar (Rost et al., 2003). LOXL2 was identified in poorly-differentiated HNSCC tumors with likely strong desmoplastic response or epithelial-mesenchymal transition, and as part of a gene set predictive of high risk of recurrence in HNSCC (Chung et al., 2004, Chung et al., 2006).
In oral squamous cell carcinoma (OSCC) tissues, there was significantly higher LOXL2 expression compared to paired normal matched tissues, and LOXL2 was part of a 25-gene predictor set to distinguish normal from OSCC tissues (Ziober et al., 2006; Shieh et al., 2007). However, there was higher LOXL2 expression in cultured normal oral mucosal cells than OSCC cells (Shieh et al., 2007).
Increased LOXL2 protein expression was reported to correlate with local recurrence, decreased overall survival and decreased disease-free survival in patients with laryngeal squamous cell carcinoma (Peinado et al., 2008).
  
  
Entity Lung cancer
Note LOXL2 was reported to be barely detectable or absent in the cultured lung small cell carcinoma cell line NCI-H69 (Saito et al., 1997). Repression of type II TGF-b receptor by siRNA in the lung carcinoma cell line H23, was associated with increased number of invasive cells and increased levels of LOXL2 mRNA (Borczuk et al., 2005). Increased LOXL2 protein expression was reported to be associated with decreased overall survival and decreased disease-free survival in patients with lung squamous cell carcinoma (Peinado et al., 2008).
  
  
Entity Malignant Mesothelioma
Note LOXL2 mRNA expression was noted to be higher in effusions due to malignant mesothelioma than in effusions due to benign reactive mesothelium (Sebban et al., 2009).
  
  
Entity Melanoma
Note LOXL2 mRNA was reported to be highly expressed in the lymph node melanoma cell line Hs294T (Saito et al., 1997). LOXL2 mRNA expression was also highly expressed in the highly invasive uveal melanoma cell lines M619 and C918, compared to absent expression in the poorly invasive uveal melanoma cell line OCM-1A (Kirschmann et al., 2002).
  
  
Entity Ovarian cancer
Note Using gene expression profiling, LOXL2 mRNA expression was reported to be down-regulated in serous ovarian adenocarcinomas compared to the mucinous ovarian cancers (Hough et al., 2000; Ono et al., 2000). However, a more recent report found LOXL2 mRNA to be expressed in all types of primary ovarian cancer tissues, including serous, clear cell, endometrioid, undifferentiated and mixed type, as well as metastases and metastatic effusions (Sebban et al., 2009).
  
  
Entity Pancreatic cancer
Note LOXL2 mRNA was upregulated in Panc1 pancreatic cancer cells compared to normal human pancreatic duct epithelial (HPDE) cells (Gronberg et al., 2006).
  
  
Entity Peripheral nerve sheath cancer
Note LOXL2 mRNA was over-expressed in high-grade malignant peripheral nerve sheath tumors, which are highly aggressive (Kresse et al., 2008).
  
  
Entity Ras-transformation
Note LOXL2 mRNA expression was down-regulated nearly 60 fold in ras-transformed fibroblasts compared to immortalized rat embryonic fibroblasts (Zuber et al., 2000).
  
  
Entity Skin cancer
Note Knockdown of LOXL2 mRNA in the mouse malignant squamous cell carcinoma cell line HaCa4 and the spindle cell carcinoma cell line CarB resulted in decreased tumor growth, increased apoptosis, re-expression of E-cadherin, decreased expression of fibronectin, vimentin and MMP-9 (Peinado et al., 2005). LOXL2 knockdown in HaCa4 also resulted in increased cell-cell contacts, elimination of in vivo invasive ability and a skin-like epidermal differentiation program with re-expression and organization of E-cadherin at suprabasal layers. Expression of LOXL2 was correlated with malignant progression in a mouse skin carcinogenesis model (Peinado et al., 2008).
  

Breakpoints

Note None involving the LOXL2 gene.

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Nakken KE, Nygard S, Haaland T, Berge KE, Arnkvaern K, Odegaard A, Labori KJ, Raeder MG.
Scand J Gastroenterol. 2007 Oct;42(10):1245-55.
PMID 17852852
 
Identification by cDNA microarray of genes involved in ovarian carcinogenesis.
Ono K, Tanaka T, Tsunoda T, Kitahara O, Kihara C, Okamoto A, Ochiai K, Takagi T, Nakamura Y.
Cancer Res. 2000 Sep 15;60(18):5007-11.
PMID 11016619
 
Comparison of replicative senescence and stress-induced premature senescence combining differential display and low-density DNA arrays.
Pascal T, Debacq-Chainiaux F, Chretien A, Bastin C, Dabee AF, Bertholet V, Remacle J, Toussaint O.
FEBS Lett. 2005 Jul 4;579(17):3651-9.
PMID 15963989
 
A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression.
Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, Nieto MA, Cano A, Portillo F.
EMBO J. 2005 Oct 5;24(19):3446-58. Epub 2005 Aug 18.
PMID 16096638
 
Lysyl oxidase-like 2 as a new poor prognosis marker of squamous cell carcinomas.
Peinado H, Moreno-Bueno G, Hardisson D, Perez-Gomez E, Santos V, Mendiola M, de Diego JI, Nistal M, Quintanilla M, Portillo F, Cano A.
Cancer Res. 2008 Jun 15;68(12):4541-50.
PMID 18559498
 
Switching on-off Snail: LOXL2 versus GSK3beta.
Peinado H, Portillo F, Cano A.
Cell Cycle. 2005 Dec;4(12):1749-52. Epub 2005 Dec 5.
PMID 16294032
 
Whole-body gene expression by data mining.
Pires Martins R, Leach RE, Krawetz SA.
Genomics. 2001 Feb 15;72(1):34-42.
PMID 11247664
 
Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells.
Qi H, Aguiar DJ, Williams SM, La Pean A, Pan W, Verfaillie CM.
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3305-10. Epub 2003 Mar 11.
PMID 12631704
 
Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas.
Rost T, Pyritz V, Rathcke IO, Gorogh T, Dunne AA, Werner JA.
Anticancer Res. 2003 Mar-Apr;23(2B):1565-73.
PMID 12820424
 
Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence.
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J Biol Chem. 1997 Mar 28;272(13):8157-60.
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Regulation of hypoxia-inducible genes by ETS1 transcription factor.
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Carcinogenesis. 2008 Aug;29(8):1493-9. Epub 2008 Apr 1.
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Sebban S, Davidson B, Reich R.
Virchows Arch. 2009 Jan;454(1):71-9. Epub 2008 Nov 18.
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Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4378-85.
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Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3209-15.
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Citation

This paper should be referenced as such :
Fong, SFT ; Fong, KSK ; Csiszar, K
LOXL2 (lysyl oxidase-like 2)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(1):29-35.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LOXL2ID41192ch8p21.html


External links

Nomenclature
HGNC (Hugo)LOXL2   6666
Cards
AtlasLOXL2ID41192ch8p21
Entrez_Gene (NCBI)LOXL2  4017  lysyl oxidase like 2
AliasesLOR; LOR2; WS9-14
GeneCards (Weizmann)LOXL2
Ensembl hg19 (Hinxton)ENSG00000134013 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000134013 [Gene_View]  chr8:23296897-23404209 [Contig_View]  LOXL2 [Vega]
ICGC DataPortalENSG00000134013
TCGA cBioPortalLOXL2
AceView (NCBI)LOXL2
Genatlas (Paris)LOXL2
WikiGenes4017
SOURCE (Princeton)LOXL2
Genetics Home Reference (NIH)LOXL2
Genomic and cartography
GoldenPath hg38 (UCSC)LOXL2  -     chr8:23296897-23404209 -  8p21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)LOXL2  -     8p21.3   [Description]    (hg19-Feb_2009)
EnsemblLOXL2 - 8p21.3 [CytoView hg19]  LOXL2 - 8p21.3 [CytoView hg38]
Mapping of homologs : NCBILOXL2 [Mapview hg19]  LOXL2 [Mapview hg38]
OMIM606663   
Gene and transcription
Genbank (Entrez)AF117949 AK098436 AK124508 AK222477 AK293292
RefSeq transcript (Entrez)NM_002318
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)LOXL2
Cluster EST : UnigeneHs.626637 [ NCBI ]
CGAP (NCI)Hs.626637
Alternative Splicing GalleryENSG00000134013
Gene ExpressionLOXL2 [ NCBI-GEO ]   LOXL2 [ EBI - ARRAY_EXPRESS ]   LOXL2 [ SEEK ]   LOXL2 [ MEM ]
Gene Expression Viewer (FireBrowse)LOXL2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4017
GTEX Portal (Tissue expression)LOXL2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y4K0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9Y4K0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y4K0
Splice isoforms : SwissVarQ9Y4K0
PhosPhoSitePlusQ9Y4K0
Domaine pattern : Prosite (Expaxy)LYSYL_OXIDASE (PS00926)    SRCR_1 (PS00420)    SRCR_2 (PS50287)   
Domains : Interpro (EBI)Lysyl_oxidase    Lysyl_oxidase_CS    SRCR    SRCR-like_dom   
Domain families : Pfam (Sanger)Lysyl_oxidase (PF01186)    SRCR (PF00530)   
Domain families : Pfam (NCBI)pfam01186    pfam00530   
Domain families : Smart (EMBL)SR (SM00202)  
Conserved Domain (NCBI)LOXL2
DMDM Disease mutations4017
Blocks (Seattle)LOXL2
SuperfamilyQ9Y4K0
Human Protein AtlasENSG00000134013
Peptide AtlasQ9Y4K0
HPRD09446
IPIIPI00294839   IPI00909789   IPI00983265   IPI00984570   IPI00973713   IPI00981947   IPI00973750   IPI00980637   IPI00982423   
Protein Interaction databases
DIP (DOE-UCLA)Q9Y4K0
IntAct (EBI)Q9Y4K0
FunCoupENSG00000134013
BioGRIDLOXL2
STRING (EMBL)LOXL2
ZODIACLOXL2
Ontologies - Pathways
QuickGOQ9Y4K0
Ontology : AmiGOresponse to hypoxia  epithelial to mesenchymal transition  endothelial cell proliferation  sprouting angiogenesis  chromatin binding  transcription corepressor activity  protein-lysine 6-oxidase activity  scavenger receptor activity  copper ion binding  protein binding  basement membrane  extracellular space  nucleus  nucleus  nucleoplasm  chromosome  transcription, DNA-templated  cellular protein modification process  receptor-mediated endocytosis  cell adhesion  aging  electron carrier activity  membrane  histone modification  protein deamination  collagen fibril organization  extracellular matrix  positive regulation of chondrocyte differentiation  methylated histone binding  endothelial cell migration  negative regulation of transcription, DNA-templated  response to copper ion  oxidation-reduction process  oligosaccharide binding  
Ontology : EGO-EBIresponse to hypoxia  epithelial to mesenchymal transition  endothelial cell proliferation  sprouting angiogenesis  chromatin binding  transcription corepressor activity  protein-lysine 6-oxidase activity  scavenger receptor activity  copper ion binding  protein binding  basement membrane  extracellular space  nucleus  nucleus  nucleoplasm  chromosome  transcription, DNA-templated  cellular protein modification process  receptor-mediated endocytosis  cell adhesion  aging  electron carrier activity  membrane  histone modification  protein deamination  collagen fibril organization  extracellular matrix  positive regulation of chondrocyte differentiation  methylated histone binding  endothelial cell migration  negative regulation of transcription, DNA-templated  response to copper ion  oxidation-reduction process  oligosaccharide binding  
REACTOMEQ9Y4K0 [protein]
REACTOME PathwaysR-HSA-2243919 [pathway]   
NDEx NetworkLOXL2
Atlas of Cancer Signalling NetworkLOXL2
Wikipedia pathwaysLOXL2
Orthology - Evolution
OrthoDB4017
GeneTree (enSembl)ENSG00000134013
Phylogenetic Trees/Animal Genes : TreeFamLOXL2
HOVERGENQ9Y4K0
HOGENOMQ9Y4K0
Homologs : HomoloGeneLOXL2
Homology/Alignments : Family Browser (UCSC)LOXL2
Gene fusions - Rearrangements
Fusion : MitelmanTUSC3/LOXL2 [8p22/8p21.3]  [t(8;8)(p21;p22)]  
Fusion: TCGATUSC3 8p22 LOXL2 8p21.3 PRAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerLOXL2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LOXL2
dbVarLOXL2
ClinVarLOXL2
1000_GenomesLOXL2 
Exome Variant ServerLOXL2
ExAC (Exome Aggregation Consortium)LOXL2 (select the gene name)
Genetic variants : HAPMAP4017
Genomic Variants (DGV)LOXL2 [DGVbeta]
DECIPHERLOXL2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisLOXL2 
Mutations
ICGC Data PortalLOXL2 
TCGA Data PortalLOXL2 
Broad Tumor PortalLOXL2
OASIS PortalLOXL2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICLOXL2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDLOXL2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch LOXL2
DgiDB (Drug Gene Interaction Database)LOXL2
DoCM (Curated mutations)LOXL2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)LOXL2 (select a term)
intoGenLOXL2
NCG5 (London)LOXL2
Cancer3DLOXL2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606663   
Orphanet
MedgenLOXL2
Genetic Testing Registry LOXL2
NextProtQ9Y4K0 [Medical]
TSGene4017
GENETestsLOXL2
Target ValidationLOXL2
Huge Navigator LOXL2 [HugePedia]
snp3D : Map Gene to Disease4017
BioCentury BCIQLOXL2
ClinGenLOXL2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4017
Chemical/Pharm GKB GenePA30429
Clinical trialLOXL2
Miscellaneous
canSAR (ICR)LOXL2 (select the gene name)
Probes
Litterature
PubMed71 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineLOXL2
EVEXLOXL2
GoPubMedLOXL2
iHOPLOXL2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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