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FLASH GENE
Symbol LCN2 contributors: mct - updated : 06-12-2014
HGNC name lipocalin 2
HGNC id 6526
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
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 840 22.5 198 - 2007
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     stomach   highly
    Endocrineadrenal gland     Homo sapiensAdult
    Nervousbrainhindbraincerebellum highly Homo sapiensFetal
    Reproductivefemale systemovary  highly
    Urinarykidneynephron    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticgranulocyte
    Blood/Hematopoieticmature hematopoietic
    Blood/Hematopoieticprogenitor cell
    Digestivestellate Homo sapiensFetal
    NervousPurkinje cell Homo sapiensFetal
    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
  • 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