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FLASH GENE
Symbol LCN2 contributors: mct - updated : 06-12-2015
HGNC name lipocalin 2
HGNC id 6526
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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    digestiveliversteatosis
    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