LCN2
Description
The LCN2 (lipocalin 2) is a protein-coding gene located on chromosome 9.
Lipocalin-2 (LCN2), also known as oncogene 24p3 or neutrophil gelatinase-associated lipocalin (NGAL), is a protein that in humans is encoded by the LCN2 gene. NGAL is involved in innate immunity by sequestering iron and preventing its use by bacteria, thus limiting their growth. It is expressed in neutrophils and in low levels in the kidney, prostate, and epithelia of the respiratory and alimentary tracts. NGAL is used as a biomarker of kidney injury.
The binding of NGAL to bacterial siderophores is important in the innate immune response to bacterial infection. Upon encountering invading bacteria, the toll-like receptors on immune cells stimulate the synthesis and secretion of NGAL. Secreted NGAL then limits bacterial growth by sequestering iron-containing siderophores. Lipocalin-2 binds, next to bacterial siderophores, also to the mammalian siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA). This complex ensures that excess free iron does not accumulate in the cytoplasm. Mammalian cells lacking 2,5-DHBA accumulate abnormal intracellular levels of iron leading to high levels of reactive oxygen species. Lipocalin-2 also functions as a growth factor and participates in synaptic plasticity.
LCN2 is an iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. It binds iron through association with 2,3-dihydroxybenzoic acid (2,3-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. The 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. LCN2 is 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. LCN2 is involved in innate immunity; it limits bacterial proliferation by sequestering iron bound to microbial siderophores, such as enterobactin. It can also bind siderophores from M.tuberculosis.
LCN2 is also known as 24p3, MSFI, NGAL, p25.
