LCN2

Lipocalin 2
PDB rendering based on 1dfv.
Available structures PDB 1DFV, 1L6M, 1NGL, 1QQS, 1X71, 1X89, 1X8U, 3BY0, 3CBC, 3CMP, 3DSZ, 3DTQ, 3FW4, 3FW5, 3HWD, 3HWE, 3HWF, 3HWG, 3I0A, 3K3L
Identifiers
Symbols	LCN2; 24p3; MSFI; NGAL
External IDs	OMIM: 600181 MGI: 96757 HomoloGene: 4064 GeneCards: LCN2 Gene
Gene Ontology Molecular function • protease binding • transporter activity • binding • iron ion binding • protein homodimerization activity Cellular component • extracellular region • extracellular space • cytosol Biological process • ion transport • response to oxidative stress • response to virus • response to bacterium • response to herbicide • positive regulation of gene expression • siderophore transport • positive regulation of cell projection organization • cellular response to nutrient levels • response to drug • regulation of apoptosis • innate immune response • iron ion homeostasis • protein homotrimerization • cellular response to hydrogen peroxide • cellular response to lipopolysaccharide • cellular response to interleukin-1 • cellular response to tumor necrosis factor • cellular response to protein stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3934	16819
Ensembl	ENSG00000148346	ENSMUSG00000026822
UniProt	P80188	Q3UE34
RefSeq (mRNA)	NM_005564.3	NM_008491.1
RefSeq (protein)	NP_005555.2	NP_032517.1
Location (UCSC)	Chr 9: 130.91 – 130.92 Mb	Chr 2: 32.24 – 32.24 Mb
PubMed search	[1]	[2]

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.^[1][2][3]

Function

The binding of lipocalin-2 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 lipocalin-2. Secreted lipocalin-2 then limits bacterial growth by sequestering iron-containing siderophores.^[4][5] Lipocalin-2 also functions as a growth factor.^[5]

NGAL is strongly upregulated during inflammation and is upregulated by interleukin 1 (but not TNF alpha) in humans. There are indications that some forms of acne could be caused due to the gene not being transcribed, and that Isotretinoin corrects this.^[6]

NFAT3 (NFATc4)[3] by blocking the expression of LCN2 inhibits breast carcinoma cell motility ^[7].

References

1. ^ Kjeldsen L, Johnsen AH, Sengeløv H, Borregaard N (May 1993). "Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase". J. Biol. Chem. 268 (14): 10425–32. PMID 7683678. 
2. ^ Chan P, Simon-Chazottes D, Mattei MG, Guenet JL, Salier JP (September 1994). "Comparative mapping of lipocalin genes in human and mouse: the four genes for complement C8 gamma chain, prostaglandin-D-synthase, oncogene-24p3, and progestagen-associated endometrial protein map to HSA9 and MMU2". Genomics 23 (1): 145–50. doi:10.1006/geno.1994.1470. PMID 7829063. 
3. ^ Cowland JB, Borregaard N (October 1997). "Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans". Genomics 45 (1): 17–23. doi:10.1006/geno.1997.4896. PMID 9339356. 
4. ^ Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A (December 2004). "Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron". Nature 432 (7019): 917–21. doi:10.1038/nature03104. PMID 15531878. 
5. ^ ^{a b} Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J (February 2007). "Dual action of neutrophil gelatinase-associated lipocalin". J. Am. Soc. Nephrol. 18 (2): 407–13. doi:10.1681/ASN.2006080882. PMID 17229907. 
6. ^ Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu W, Thiboutot DM (April 2008). "Neutrophil gelatinase–associated lipocalin mediates 13-cis retinoic acid–induced apoptosis of human sebaceous gland cells". J. Clin. Invest. 118 (4): 1468–78. doi:10.1172/JCI33869. PMC 2262030. PMID 18317594. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2262030. 
7. ^ Fougère, M; Gaudineau, B, Barbier, J, Guaddachi, F, Feugeas, JP, Auboeuf, D, Jauliac, S (2010 Apr 15). "NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene.". Oncogene 29 (15): 2292–301. PMID 20101218. 

Further reading

• Triebel S, Bläser J, Reinke H, Tschesche H (1993). "A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 kDa form of human gelatinase". FEBS Lett. 314 (3): 386–8. doi:10.1016/0014-5793(92)81511-J. PMID 1281792. 
• Bläser J, Triebel S, Tschesche H (1995). "A sandwich enzyme immunoassay for the determination of neutrophil lipocalin in body fluids". Clin. Chim. Acta 235 (2): 137–45. doi:10.1016/0009-8981(95)06020-7. PMID 7554268. 
• Bartsch S, Tschesche H (1995). "Cloning and expression of human neutrophil lipocalin cDNA derived from bone marrow and ovarian cancer cells". FEBS Lett. 357 (3): 255–9. doi:10.1016/0014-5793(94)01303-I. PMID 7835423. 
• Xu SY, Carlson M, Engström A et al. (1995). "Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils". Scand. J. Clin. Lab. Invest. 54 (5): 365–76. doi:10.3109/00365519409088436. PMID 7997842. 
• Bundgaard JR, Sengeløv H, Borregaard N, Kjeldsen L (1994). "Molecular cloning and expression of a cDNA encoding NGAL: a lipocalin expressed in human neutrophils". Biochem. Biophys. Res. Commun. 202 (3): 1468–75. doi:10.1006/bbrc.1994.2096. PMID 8060329. 
• Xu SY, Petersson CG, Carlson M, Venge P (1994). "The development of an assay for human neutrophil lipocalin (HNL)--to be used as a specific marker of neutrophil activity in vivo and vitro". J. Immunol. Methods 171 (2): 245–52. doi:10.1016/0022-1759(94)90044-2. PMID 8195592. 
• Axelsson L, Bergenfeldt M, Ohlsson K (1996). "Studies of the release and turnover of a human neutrophil lipocalin". Scand. J. Clin. Lab. Invest. 55 (7): 577–88. doi:10.3109/00365519509110257. PMID 8633182. 
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
• Stoesz SP, Friedl A, Haag JD et al. (1998). "Heterogeneous expression of the lipocalin NGAL in primary breast cancers". Int. J. Cancer 79 (6): 565–72. doi:10.1002/(SICI)1097-0215(19981218)79:6<565::AID-IJC3>3.0.CO;2-F. PMID 9842963. 
• Coles M, Diercks T, Muehlenweg B et al. (1999). "The solution structure and dynamics of human neutrophil gelatinase-associated lipocalin". J. Mol. Biol. 289 (1): 139–57. doi:10.1006/jmbi.1999.2755. PMID 10339412. 
• Friedl A, Stoesz SP, Buckley P, Gould MN (1999). "Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues. Cell type-specific pattern of expression". Histochem. J. 31 (7): 433–41. doi:10.1023/A:1003708808934. PMID 10475571. 
• Rudd PM, Mattu TS, Masure S et al. (1999). "Glycosylation of natural human neutrophil gelatinase B and neutrophil gelatinase B-associated lipocalin". Biochemistry 38 (42): 13937–50. doi:10.1021/bi991162e. PMID 10529240. 
• Goetz DH, Willie ST, Armen RS et al. (2000). "Ligand preference inferred from the structure of neutrophil gelatinase associated lipocalin". Biochemistry 39 (8): 1935–41. doi:10.1021/bi992215v. PMID 10684642. 
• Dias Neto E, Correa RG, Verjovski-Almeida S et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16267. 
• Zerega B, Cermelli S, Michelis B et al. (2000). "Expression of NRL/NGAL (neu-related lipocalin/neutrophil gelatinase-associated lipocalin) during mammalian embryonic development and in inflammation". Eur. J. Cell Biol. 79 (3): 165–72. doi:10.1078/S0171-9335(04)70019-9. PMID 10777108. 
• Devireddy LR, Teodoro JG, Richard FA, Green MR (2001). "Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation". Science 293 (5531): 829–34. doi:10.1126/science.1061075. PMID 11486081.