General Information of Drug Therapeutic Target (DTT) (ID: TTKTLAI)

DTT Name Neutrophil gelatinase-associated lipocalin (LCN2)
Synonyms p25; Siderocalin LCN2; Oncogene 24p3; NGAL; Lipocalin-2; LCN2; 25 kDa alpha-2-microglobulin-related subunit of MMP-9
Gene Name LCN2
DTT Type
Literature-reported target
[1]
BioChemical Class
Calycin family
UniProt ID
NGAL_HUMAN
TTD ID
T72010
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPLGLLWLGLALLGALHAQAQDSTSDLIPAPPLSKVPLQQNFQDNQFQGKWYVVGLAGNA
ILREDKDPQKMYATIYELKEDKSYNVTSVLFRKKKCDYWIRTFVPGCQPGEFTLGNIKSY
PGLTSYLVRVVSTNYNQHAMVFFKKVSQNREYFKITLYGRTKELTSELKENFIRFSKSLG
LPENHIVFPVPIDQCIDG
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. .
KEGG Pathway
IL-17 signaling pathway (hsa04657 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Metal sequestration by antimicrobial proteins (R-HSA-6799990 )
Iron uptake and transport (R-HSA-917937 )
Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 )

References

1 Biomarkers of diabetic nephropathy, the present and the future. Curr Diabetes Rev. 2012 Sep;8(5):317-28.