InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LCN2

Summary

InnateDB Protein

IDBP-87417.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LCN2

Protein Name

lipocalin 2

Synonyms

24p3; MSFI; NGAL;

Species

Homo sapiens

Ensembl Protein

ENSP00000362108

InnateDB Gene

IDBG-87415 (LCN2)

Protein Structure

UniProt Annotation

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 with bacterial 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. {ECO:0000269PubMed:12453413}.

Subcellular Localization

Secreted {ECO:0000269PubMed:12453413}. Note=Upon binding to the SLC22A17 (24p3R) receptor, it is internalized.

Disease Associations

Tissue Specificity

Expressed in bone marrow and in tissues that are prone to exposure to microorganism. High expression is found in bone marrow as well as in uterus, prostate, salivary gland, stomach, appendix, colon, trachea and lung. Not found in the small intestine or peripheral blood leukocytes. {ECO:0000269PubMed:9339356}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 12 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	12 [view]
Protein-Protein	7 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0005215	transporter activity
GO:0005506	iron ion binding
GO:0005515	protein binding
GO:0036094	small molecule binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0006811	ion transport
GO:0006979	response to oxidative stress
GO:0009615	response to virus
GO:0009617	response to bacterium
GO:0009635	response to herbicide
GO:0009636	response to toxic substance
GO:0010628	positive regulation of gene expression
GO:0015891	siderophore transport
GO:0031346	positive regulation of cell projection organization
GO:0031667	response to nutrient levels
GO:0031669	cellular response to nutrient levels
GO:0042493	response to drug
GO:0045087	innate immune response (InnateDB)
GO:0070207	protein homotrimerization
GO:0070301	cellular response to hydrogen peroxide
GO:0071222	cellular response to lipopolysaccharide
GO:0071347	cellular response to interleukin-1
GO:0071356	cellular response to tumor necrosis factor
GO:0097192	extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005829	cytosol
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000566 Lipocalin/cytosolic fatty-acid binding domain
IPR002345 Lipocalin
IPR002968 Alpha-1-microglobulin
IPR002972 Prostaglandin D synthase
IPR003087 Neutrophil gelatinase-associated lipocalin
IPR011038 Calycin-like

PFAM

PF00061
PF08212

PRINTS

PR00179
PR01215
PR01254
PR01275

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P80188