Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

LCN2

contributors: mct - updated : 06-12-2015

HGNC name	lipocalin 2
HGNC id	6526

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	9q34.11      Physical location : 130.911.731 - 130.915.734
Synonym name	neutrophil gelatinase-associated lipocalin
	lipocalin 2 (oncogene 24p3)
	siderocalin
	25 kDa alpha-2-microglobulin-related subunit of MMP-9
Synonym symbol(s)	NGAL, 24P3, p25, HNL, MSFI, 24p3

DNA

TYPE	functioning gene
STRUCTURE	4.39 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   HRE
text structure	glucocorticoid response element

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005564 7 - 840 NP_005555 22.5 198 - 2007

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly   stomach       highly Endocrine adrenal gland         Homo sapiens Adult Nervous brain hindbrain cerebellum   highly Homo sapiens Fetal Reproductive female system ovary     highly Urinary kidney nephron       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective bone

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic granulocyte Blood/Hematopoietic mature hematopoietic Blood/Hematopoietic progenitor cell Digestive stellate Homo sapiens Fetal Nervous Purkinje cell Homo sapiens Fetal

cell lineage
cell lines
fluid/secretion	saliva

at STAGE

physiological period

fetal

Text	lung, spleen

PROTEIN

PHYSICAL PROPERTIES		Hydrophilic
STRUCTURE

motifs/domains

a single eight-stranded continuously hydrogen-bunded antiparallel beta-barrel which encloses an internal ligand binding site

HOMOLOGY

Homologene

FAMILY	lipophilic ligand carrier protein superfamily
	calycin superfamily
	lipocalin family

CATEGORY

secretory , tumor suppressor , transport carrier

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm

basic FUNCTION	involved in the transport of hydrophobic ligands (retinol transport)and of small lipophilic substances
	modulator of inflammation (prostaglandin synthesis)
	immune system homeostasis
	suppressing growth induced by IL3, but not influencing CSF3-dependent cell growth
	iron-siderophore-binding protein, converting embryonic kidney mesenchyme to epithelia
	epithelial inducer in Ras malignancy and suppressor of metastasis
	iron transporter with functions distinct from that of transferrin and mediating a new iron-delivery pathway
	lineage-specific role in hematopoiesis, having important function in the regulation of hematopoiesis
	adipokine that potentially connects obesity and its related adipose inflammation
	autocrine and paracrine adipokine, acts as an antagonist to the effect of inflammatory molecules on inflammation and secretion of adipokines
	potential suppressor of invasion and angiogenesis in advanced pancreatic cancer
	important biomarker in clinical nephrology, extending to chronic kidney disease the pathophysiological role of this protein in tubular adaptations to renal damage
	plays a role as an iron-sequestering protein in the antibacterial innate immune response
	induces apoptosis in some types of cells and inhibits bacterial growth by sequestration of the iron-laden bacterial siderophore
	may actively participate in breast cancer progression
	siderophore-binding antimicrobial protein, critical for control of systemic infection with Escherichia coli
	being a crucial component of mucosal immune defense against pulmonary infection with K. pneumoniae
	critical selective modulator of PPARG activation and function in lipid homeostasis and energy expenditure 8)
	SLC22A17, in cooperation with LCN2, is involved in the acquisition of aggressive behavior among endometrial carcinoma cells
	controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation
	promotes cell migration through up-regulation of chemokines in brain
	essential role for LCN2 as a protein required for the reactive astrocytosis and cell migration in the CNS
	LCN2 accelerated neuronal motility and process extension, suggesting multiple roles for LCN2 in the regulation of neuronal cell death, migration, and morphology
	LCN2-induced cardiomyocyte apoptosis is of physiological significance and occurs via a mechanism involving elevated intracellular iron levels and BAX translocation
	is a molecular actor in neuroinflammation in early clinical stages of Alzheimer disease
	novel role as an important paracrine chemoattractant and an indispensable factor for neutrophil function in inflammation
	promotes angiogenesis, suggesting a novel mechanism through which LCN2 may promote tumor progression
	STEAP4 and LCN2 mRNA and protein levels in visceral adipose tissue are related to iron status
	is an M1-amplifier in brain microglial cells

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

inflammation

PATHWAY

metabolism

signaling

a component	constituent of human tear
	covalently linked, disulfide-bridged heterodimer with the 92 kda type v collagenase, MMP9

INTERACTION

DNA

RNA

small molecule

protein	with IL3
	CXCL10 plays a central role in LCN2-induced cell migration (key role for LCN2-CXCL10 axis in cell migration and reactive astrocytosis following brain inflammation or injury)
	JAK2/STAT3 signaling pathway appears to play a pivotal role in the LCN2 action in astrocytes
	is a new DDIT3 target gene that mediates ER stress-induced apoptosis
	LCN2-induced VEGFA is mediated through hypoxia-inducible factor 1&
	945; (HIF1A) and LCN2 regulates HIF1A through extracellular signal-regulated kinase (Erk)
	LCN2 is the key secreted factor downstream of TCF3 that promotes cell migration and wound healing
	LCN2 is a key modulator of hepatic lipid homeostasis that controls the formation of intracellular lipid droplets by regulating PLIN5 expression
	thrombin upregulates LCN2 through F2R activation and causes brain damage in brain injury
	NEGR1 interacts with leukemia inhibitory factor receptor (LIFR) and modulates LIF-induced LCN2 expression

cell & other

REGULATION

induced by

IL3 deprivation (induction of hematopoietic cells apoptosis)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in ulcerative colitis tumoral     --low   in gastric cancer tumoral     --over   consistently associated with invasive breast cancer tumoral       gain of function in multiple cancers, including breast, lung, and pancreas tumoral     --over   of SLC22A17 and LCN2 was found to be significantly associated with poor prognosis in glioma

Susceptibility

Variant & Polymorphism

Candidate gene	useful biomarker of breast cancer (Lcn2 levels might be elevated in the urine of women with breast cancer; increase in the urine of women with metastatic breast cancer, suggesting that Lcn2 may have potential as a noninvasive biomarker for advanced breast cancer)
Marker	increased plasma LCN2 levels during mild cognitive impairment (MCI) could be helpful in predicting the progression from MCI to Alzheimer disease
	HIC1-LCN2 axis may serve as a subtype-specific prognostic biomarker in triple-negative breast cancer
	urinary MMP9/LCN2 and ADAM12 are potential noninvasive biomarkers for gastric cancer, including early-stage disease
Therapy target
	System Type Disorder Pubmed digestive liver steatosis novel therapeutic drug target for the treatment of liver diseases associated with elevated fat accumulation and steatosis

ANIMAL & CELL MODELS

lipocalin-2-deficient mice have increased susceptibility to bacterial infections in the urinary tract