Target Information
Target General Information | Top | |||||
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Target ID |
T25637
(Former ID: TTDI02115)
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Target Name |
Lysyl oxidase homolog 2 (LOXL2)
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Synonyms |
Lysyl oxidaserelated protein WS914; Lysyl oxidaserelated protein 2; Lysyl oxidaselike protein 2; LOXL2
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Gene Name |
LOXL2
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Colorectal cancer [ICD-11: 2B91] | |||||
Function |
Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine). When secreted in extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding. When nuclear, acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation. Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E- cadherin, probably by mediating deamination of histone H3. Also involved in E-cadherin repression following hypoxia, a hallmark of epithelial to mesenchymal transition believed to amplify tumor aggressiveness, suggesting that it may play a role in tumor progression. Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation.
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UniProt ID | ||||||
EC Number |
EC 1.4.3.13
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Sequence |
MERPLCSHLCSCLAMLALLSPLSLAQYDSWPHYPEYFQQPAPEYHQPQAPANVAKIQLRL
AGQKRKHSEGRVEVYYDGQWGTVCDDDFSIHAAHVVCRELGYVEAKSWTASSSYGKGEGP IWLDNLHCTGNEATLAACTSNGWGVTDCKHTEDVGVVCSDKRIPGFKFDNSLINQIENLN IQVEDIRIRAILSTYRKRTPVMEGYVEVKEGKTWKQICDKHWTAKNSRVVCGMFGFPGER TYNTKVYKMFASRRKQRYWPFSMDCTGTEAHISSCKLGPQVSLDPMKNVTCENGLPAVVS CVPGQVFSPDGPSRFRKAYKPEQPLVRLRGGAYIGEGRVEVLKNGEWGTVCDDKWDLVSA SVVCRELGFGSAKEAVTGSRLGQGIGPIHLNEIQCTGNEKSIIDCKFNAESQGCNHEEDA GVRCNTPAMGLQKKLRLNGGRNPYEGRVEVLVERNGSLVWGMVCGQNWGIVEAMVVCRQL GLGFASNAFQETWYWHGDVNSNKVVMSGVKCSGTELSLAHCRHDGEDVACPQGGVQYGAG VACSETAPDLVLNAEMVQQTTYLEDRPMFMLQCAMEENCLSASAAQTDPTTGYRRLLRFS SQIHNNGQSDFRPKNGRHAWIWHDCHRHYHSMEVFTHYDLLNLNGTKVAEGHKASFCLED TECEGDIQKNYECANFGDQGITMGCWDMYRHDIDCQWVDITDVPPGDYLFQVVINPNFEV AESDYSNNIMKCRSRYDGHRIWMYNCHIGGSFSEETEKKFEHFSGLLNNQLSPQ Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | GS-6624 | Drug Info | Phase 2 | Colorectal cancer | [2] | |
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | Beta-aminopropionitrile | Drug Info | Preclinical | Cardiac arrest | [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | Beta-aminopropionitrile | Drug Info | [4] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 3.90E-04 |
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Closeness centrality | 2.00E-01 | Radiality | 1.35E+01 | Clustering coefficient | 2.00E-01 |
Neighborhood connectivity | 1.02E+01 | Topological coefficient | 2.45E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
References | Top | |||||
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REF 1 | National Cancer Institute Drug Dictionary (drug id 681814). | |||||
REF 2 | ClinicalTrials.gov (NCT01769196) A Phase 2 Study to See if Simtuzumab (GS-6624) is Safe and Works in Idiopathic Pulmonary Fibrosis (IPF). U.S. National Institutes of Health. | |||||
REF 3 | Drugs and Targets in Fibrosis. Front Pharmacol. 2017 Nov 23;8:855. | |||||
REF 4 | Wnt signaling and Loxl2 promote aggressive osteosarcoma. Cell Res. 2020 Oct;30(10):885-901. |
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