TISIDB

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
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 [ TOP ]
There is no record.

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
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

[ TOP ]

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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
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

[ TOP ]

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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-1.339	0.00967
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.262	0.226
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.651	0.601
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.397	0.299
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.878	0.676
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.216	0.939
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.408	0.473
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.305	0.838
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.537	0.741
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.858	0.609
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	2.075	0.389
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.241	0.137

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	4.1	-4.1	0.561
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	5.1	-5.1	0.549
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	5.9	3.6	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
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 [ TOP ]

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of LOXL2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between LOXL2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	LOXL2
Name	lysyl 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 Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting LOXL2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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