Tchem LOXL2 Lysyl oxidase homolog 2

Protein Summary

Description

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). 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. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9Y4K0
• B2R5Q0
• Q53HV3
• Q9BW70
• Q9Y5Y8

Gene Name

• LOXL2

Ensembl ID

• ENST00000389131
• ENSP00000373783
• ENSG00000134013

Symbol

• LOR
• LOR2
• WS9-14

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.91
molecular function	0.9
biological process	0.89
PubMedID	0.85
transcription factor perturbation	0.8

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 216.53   (req: < 5)

Gene RIFs: 85   (req: <= 3)

Antibodies: 411   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 216.53   (req: >= 5)

Gene RIFs: 85   (req: > 3)

Antibodies: 411   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 227

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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Approved Drugs (2)

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1 – 2 of 2

disulfiram

LOXL2Tchem Enzyme

INHIBITOR :

thiram

LOXL2Tchem Enzyme

pIC50 : 6.96

Active Ligands (227)

Explore Active Ligands

1 – 10 of 227

beta-aminopropionitrile

LOXL2Tchem Enzyme

pIC50 : 7.18

CHEMBL4568508,CHEMBL4444826

LOXL2Tchem Enzyme

pIC50 : 7.16

CHEMBL4569453

LOXL2Tchem Enzyme

pIC50 : 7.3

CHEMBL4457578

LOXL2Tchem Enzyme

pKi : 7.08

CHEMBL4515085,CHEMBL4456063

LOXL2Tchem Enzyme

pIC50 : 7.55

CHEMBL4564517

LOXL2Tchem Enzyme

pIC50 : 6.72

benzo[b]thiophen-2-ylmethanamine

LOXL2Tchem Enzyme

pKi : 8

CHEMBL4531065

LOXL2Tchem Enzyme

pIC50 : 7.7

(2-chloropyridin-4-yl)methanamine

LOXL2Tchem Enzyme

pIC50 : 6.9

CHEMBL4448713

LOXL2Tchem Enzyme

pIC50 : 8.3

Protein-Protein Interactions (75)

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1 – 10 of 75

• See Interactions on String-DB

LYZL2

Tdark

Family:  Enzyme

Novelty:  0.50542161

p_int:  0.999467121

p_ni:  0.000532867

p_wrong:  1.2e-8

Data Source:  BioPlex

RBM14

Tbio

Novelty:  0.01286049

p_int:  0.999274461

p_ni:  0.000725536

p_wrong:  3e-9

Data Source:  BioPlex

DEFA1

Tbio

Novelty:  0.01027492

p_int:  0.997871404

p_ni:  0.002128575

p_wrong:  2.1e-8

Data Source:  BioPlex

MFAP5

Tbio

Novelty:  0.01839035

p_int:  0.99772418

p_ni:  0.002275428

p_wrong:  3.93e-7

Score:  0.907

Data Source:  BioPlex,STRINGDB

KLK11

Tbio

Family:  Enzyme

Novelty:  0.00267977

p_int:  0.995782846

p_ni:  0.004217154

Data Source:  BioPlex

CSTL1

Tbio

Novelty:  0.13370814

p_int:  0.992981367

p_ni:  0.007016735

p_wrong:  0.000001897

Data Source:  BioPlex

WNT7A

Tbio

Novelty:  0.00421662

p_int:  0.991755658

p_ni:  0.008244342

Data Source:  BioPlex

PSG8

Tdark

Novelty:  0.1446257

p_int:  0.991415203

p_ni:  0.008555144

p_wrong:  0.000029653

Data Source:  BioPlex

TMEM87A

Tdark

Novelty:  0.33614983

p_int:  0.989351306

p_ni:  0.010646455

p_wrong:  0.000002239

Data Source:  BioPlex

ADAMTS4

Tchem

Family:  Enzyme

Novelty:  0.00424194

p_int:  0.988005138

p_ni:  0.011985389

p_wrong:  0.000009472

Score:  0.161

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (100)

Reactome (5)

WikiPathways (95)

Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Assembly of collagen fibrils and other multimeric structures	57 targets	R-HSA-2022090
Reactome	Collagen formation	90 targets	R-HSA-1474290
Reactome	Crosslinking of collagen fibrils	10 targets	R-HSA-2243919
Reactome	Elastic fibre formation	41 targets	R-HSA-1566948
Reactome	Extracellular matrix organization	297 targets	R-HSA-1474244

Name	Explore in Pharos	Explore in Source
Assembly of collagen fibrils and other multimeric structures	57 targets	R-HSA-2022090
Collagen formation	90 targets	R-HSA-1474290
Crosslinking of collagen fibrils	10 targets	R-HSA-2243919
Elastic fibre formation	41 targets	R-HSA-1566948
Extracellular matrix organization	297 targets	R-HSA-1474244

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (31)

Functions (6)

Components (8)

Processes (17)

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1 – 6 of 6

GO Term	Evidence	Assigned by
calcium ion binding	Inferred from Direct Assay (IDA)	UniProtKB
copper ion binding	Inferred from Direct Assay (IDA)	UniProtKB
oligosaccharide binding	Inferred from Direct Assay (IDA)	UniProtKB
protein-lysine 6-oxidase activity	Inferred from Direct Assay (IDA)	UniProtKB
electron transfer activity	Traceable Author Statement (TAS)	UniProtKB
scavenger receptor activity	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations ()

No disease associations found

GWAS Traits (20)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body height	EFO_0004339	1	2	2		77.6
mean platelet volume	EFO_0004584	2	2	2		75.5
age-related macular degeneration	EFO_0001365	4	2	0	1.1	68.5
hemoglobin measurement	EFO_0004509	3	2	3		67.5
appendicular lean mass	EFO_0004980	2	1	2		67.1

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body height	EFO_0004339	2		77.6
mean platelet volume	EFO_0004584	2		75.5
age-related macular degeneration	EFO_0001365	0	1.1	68.5
hemoglobin measurement	EFO_0004509	3		67.5
appendicular lean mass	EFO_0004980	2		67.1

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Basement membrane
Calcium
Chromatin regulator
Chromosome
Complete proteome
Copper
Disulfide bond
Endoplasmic reticulum
Extracellular matrix

GWAS Trait Find Similar Targets

No Header	No Header
age-related macular degeneration
appendicular lean mass
atrophic macular degeneration
birth weight
blood protein measurement
body height
body mass index
central corneal thickness
central serous retinopathy
ferritin measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging
neoplasm

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	ectonucleoside triphosphate diphosphohydrolase 4 [Source:RefSeq peptide;Acc:NP_001248494]
Mouse	lysyl oxidase-like 2	MGI:2137913	94352
Rat	lysyl oxidase-like 2	RGD:1308435	290350
Dog	lysyl oxidase like 2	VGNC:42739	486118
Horse	lysyl oxidase like 2	VGNC:19724	100058083

Species	Name	OMA	EggNOG	Inparanoid
Macaque	ectonucleoside triphosphate diphosphohydrolase 4 [Source:RefSeq peptide;Acc:NP_001248494]
Mouse	lysyl oxidase-like 2
Rat	lysyl oxidase-like 2
Dog	lysyl oxidase like 2
Horse	lysyl oxidase like 2

Publication Statistics

PubMed Score 216.53

PubMed score by year

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PubTator Score 117.12

PubTator score by year

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Related Publications

Text Mined References (100)

GeneRif Annotations (85)

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PMID	Year	Title