Browse LOXL2

Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted, extracellular space, extracellular matrix, basement membrane Nucleus Chromosome Endoplasmic reticulum Note=Associated with chromatin (PubMed:27735137). It is unclear how LOXL2 is nuclear as it contains a signal sequence and has been shown to be secreted (PubMed:23319596). However, a number of reports confirm its intracellular location and its key role in transcription regulation (PubMed:22204712, PubMed:22483618).
Domain PF01186 Lysyl oxidase
PF00530 Scavenger receptor cysteine-rich domain
Function

Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine) (PubMed:27735137). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation (PubMed:27735137). Shows no activity against histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27' (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated (H3K4me2) (PubMed:27735137). Also mediates deamination of methylated TAF10, a member of the transcription factor IID (TFIID) complex, which induces release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription (PubMed:25959397). LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and SOX2 (By similarity). Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E-cadherin CDH1, probably by mediating deamination of histone H3 (PubMed:16096638, PubMed:27735137, PubMed:24414204). During EMT, involved with SNAI1 in negatively regulating pericentromeric heterochromatin transcription (PubMed:24239292). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (PubMed:24239292). Interacts with the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1 pathway of the unfolded protein response, leading to expression of several transcription factors involved in EMT and subsequent EMT induction (PubMed:28332555). Involved in E-cadherin repression following hypoxia, a hallmark of EMT believed to amplify tumor aggressiveness, suggesting that it may play a role in tumor progression (PubMed:20026874). When secreted into the extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:20306300). Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding (PubMed:21835952). Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation (By similarity).

> Gene Ontology
 
Biological Process GO:0001501 skeletal system development
GO:0001525 angiogenesis
GO:0001666 response to hypoxia
GO:0001667 ameboidal-type cell migration
GO:0001837 epithelial to mesenchymal transition
GO:0001935 endothelial cell proliferation
GO:0002040 sprouting angiogenesis
GO:0002062 chondrocyte differentiation
GO:0006898 receptor-mediated endocytosis
GO:0007568 aging
GO:0010035 response to inorganic substance
GO:0010038 response to metal ion
GO:0010631 epithelial cell migration
GO:0016570 histone modification
GO:0018277 protein deamination
GO:0030198 extracellular matrix organization
GO:0030199 collagen fibril organization
GO:0032330 regulation of chondrocyte differentiation
GO:0032332 positive regulation of chondrocyte differentiation
GO:0036293 response to decreased oxygen levels
GO:0043062 extracellular structure organization
GO:0043542 endothelial cell migration
GO:0046688 response to copper ion
GO:0048514 blood vessel morphogenesis
GO:0048762 mesenchymal cell differentiation
GO:0050673 epithelial cell proliferation
GO:0051216 cartilage development
GO:0060485 mesenchyme development
GO:0061035 regulation of cartilage development
GO:0061036 positive regulation of cartilage development
GO:0061448 connective tissue development
GO:0070482 response to oxygen levels
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:1990267 response to transition metal nanoparticle
Molecular Function GO:0003682 chromatin binding
GO:0003714 transcription corepressor activity
GO:0004720 protein-lysine 6-oxidase activity
GO:0005044 scavenger receptor activity
GO:0005507 copper ion binding
GO:0009055 electron carrier activity
GO:0016638 oxidoreductase activity, acting on the CH-NH2 group of donors
GO:0016641 oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor
GO:0030246 carbohydrate binding
GO:0035064 methylated histone binding
GO:0038024 cargo receptor activity
GO:0042393 histone binding
GO:0070492 oligosaccharide binding
Cellular Component GO:0005578 proteinaceous extracellular matrix
GO:0005604 basement membrane
GO:0044420 extracellular matrix component
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-2022090: Assembly of collagen fibrils and other multimeric structures
R-HSA-1474290: Collagen formation
R-HSA-2243919: Crosslinking of collagen fibrils
R-HSA-1566948: Elastic fibre formation
R-HSA-1474244: Extracellular matrix organization
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between LOXL2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.

Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of LOXL2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of LOXL2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-1.3390.00967
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-2.2620.226
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.6510.601
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3970.299
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.8780.676
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2160.939
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4080.473
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3050.838
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.5370.741
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8580.609
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 282.0750.389
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2410.137
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of LOXL2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277304.1-4.10.561
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275905.1-5.10.549
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.55.93.61
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LOXL2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LOXL2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LOXL2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LOXL2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of LOXL2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between LOXL2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolLOXL2
Namelysyl oxidase-like 2
Aliases WS9-14; LOR2; lysyl oxidase related 2; lysyl oxidase-like 2 delta e13; lysyl oxidase-like 2 protein; lysyl o ......
Chromosomal Location8p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting LOXL2 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.