Target Information
| Target General Information | Top | |||||
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| Target ID |
T72010
(Former ID: TTDNR00711)
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| Target Name |
Neutrophil gelatinase-associated lipocalin (LCN2)
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| Synonyms |
p25; Siderocalin LCN2; Oncogene 24p3; NGAL; Lipocalin-2; LCN2; 25 kDa alpha-2-microglobulin-related subunit of MMP-9
Click to Show/Hide
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| Gene Name |
LCN2
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5- DHBA), a siderophore that shares structural similarities withbacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth. .
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| BioChemical Class |
Calycin family
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| UniProt ID | ||||||
| Sequence |
MPLGLLWLGLALLGALHAQAQDSTSDLIPAPPLSKVPLQQNFQDNQFQGKWYVVGLAGNA
ILREDKDPQKMYATIYELKEDKSYNVTSVLFRKKKCDYWIRTFVPGCQPGEFTLGNIKSY PGLTSYLVRVVSTNYNQHAMVFFKKVSQNREYFKITLYGRTKELTSELKENFIRFSKSLG LPENHIVFPVPIDQCIDG Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T37JN5 | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Colchicine | Ligand Info | |||||
| Structure Description | Crystal structure of an Anticalin-colchicine complex | PDB:5NKN | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [2] |
| PDB Sequence |
SDLIPAPPLS
14 KVPLQQNFQD24 NQFHGKWYVV34 GVAGNGFLRE44 DKDPIKMAAT54 IYELKEDKSY 64 NVTFQKFPMK74 KCQYMTDTLV84 PGSQPGEFTL94 GNIKSEPGYT104 SWLVRVVSTN 114 YNQHAMVFFK124 AVQQNREDFF134 ITLYGRTKEL144 TSELKENFIR154 FSKSLGLPEN 164 HIVFPVPIDQ174 CI
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VAL33
4.534
VAL36
4.605
GLY40
3.729
PHE41
3.655
MET51
4.521
THR54
4.601
TYR56
4.045
VAL66
3.667
PHE68
3.580
GLN69
3.589
LYS70
3.364
PHE71
2.739
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| Ligand Name: Catechol | Ligand Info | |||||
| Structure Description | Crystal structure of Siderocalin (NGAL, Lipocalin 2) complexed with Ferric Catechol | PDB:3FW4 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [3] |
| PDB Sequence |
SDLIPAPPLS
14 KVPLQQNFQD24 NQFQGKWYVV34 GLAGNAILRE44 DKDPQKMYAT54 IYELKEDKSY 64 NVTSVLFRKK74 KCDYWIRTFV84 PGSQPGEFTL94 GNIKSYPGLT104 SYLVRVVSTN 114 YNQHAMVFFK124 KVSQNREYFK134 ITLYGRTKEL144 TSELKENFIR154 FSKSLGLPEN 164 HIVFPVPIDQ174 CIDG
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| IL-17 signaling pathway | hsa04657 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 10 | Degree centrality | 1.07E-03 | Betweenness centrality | 3.04E-04 |
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| Closeness centrality | 2.06E-01 | Radiality | 1.36E+01 | Clustering coefficient | 3.11E-01 |
| Neighborhood connectivity | 2.24E+01 | Topological coefficient | 1.73E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Biomarkers of diabetic nephropathy, the present and the future. Curr Diabetes Rev. 2012 Sep;8(5):317-28. | |||||
| REF 2 | An engineered lipocalin that tightly complexes the plant poison colchicine for use as antidote and in bioanalytical applications. Biol Chem. 2019 Feb 25;400(3):351-366. | |||||
| REF 3 | Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat Chem Biol. 2010 Aug;6(8):602-9. | |||||
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