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FLASH GENE
Symbol LOXL2 contributors: mct - updated : 27-04-2015
HGNC name lysyl oxidase-like 2
HGNC id 6666
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systembreast    Homo sapiens
 male systemprostate   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone  highly
Muscularstriatumskeletal highly
cells
SystemCellPubmedSpeciesStageRna symbol
not specificchondrocyte Homo sapiens
Reproductiveepithelial cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four scavenger receptor cysteine-rich (SRCR) domains in the N-terminus
  • N-glycosylated protein, where N-linked glycans at Asn-455 and Asn-644 that are each essential for protein stability (
  • C-terminal lysyl oxidase (LOX) catalytic domain, sharing extensive homology with the conserved copper-binding and catalytic domains of LOX but lacking a signal sequence
  • conjugated MetalloP
    HOMOLOGY
    Homologene
    FAMILY lysyl oxidase family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • extracellular, copper-dependent enzyme that initiates the cross-linking of collagens and elastin by catalyzing the oxidative deamination of peptidyl lysine to alpha-aminoadipic-delta-semialdehyde
  • plays an essential role in the formation of extracellular matrix and connective tissue
  • plays a part in epithelial-mesenchymal transition (EMT) by stabilizing the transcription factor SNAI1
  • functions as an amine oxidase for formation of lysine-derived cross-links found in collagen and elastin
  • promotes invasion in breast cancer by regulating the expression and activity of the extracellular proteins tissue inhibitor of metalloproteinase-1 (TIMP1) and matrix metalloproteinase-9 (MMP9)
  • induces epithelial to mesenchymal transition and promotes invasiveness
  • its expression is required for ATDC5 chondrocyte cell line differentiation through regulation of SNAIL and SOX9, important transcription factors that control chondrocyte differentiation
  • promotes chondrocyte differentiation by mechanisms that are likely to include roles as both a regulator and an effector of chondrocyte differentiation
  • likely playing a vital role in chondrogenesis
  • inhibits the differentiation of keratinocytes promoting development of squamous cell carcinomas, but its enzymatic activity is not required for LOXL2-induced inhibition of keratinocyte differentiation
  • having intracellular functions, such as its involvement in the regulation of the epithelial-to-mesenchymal transition, epithelial cell polarity and differentiation mediated by transcriptional repression mechanisms
  • matrix-remodeling enzyme shown to play a key role in invasion and metastasis of breast carcinoma cells
  • tumor- secreted LOXL2 activated fibroblasts through integrin-mediated focal adhesion kinase activation
  • controls tumor-associated cell proliferation through the interaction with MARCKSL1
  • critical intracellular role for LOX and LOXL2 in transcriptional regulation
  • likely regulating extracellular and intracellular cell signaling pathways
  • involved in a wide range of physiological and pathological processes, including fibrosis and tumor progression, implicating intracellular and extracellular functions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • copper Cu2+
  • lysine tyrosylquinone
  • protein
  • interacts and cooperates with SNAI1, a transcription factor, to down-regulate E-cadherin expression that might play a role in tumor progression
  • LOXL2 activity is linked with the transcriptional control of CDH1 gene by regulating H3K4me3 deamination
  • SNAI1 regulates heterochromatin transcription through LOXL2, thus creating the favorable transcriptional state necessary for completing EMT (epithelial-to-mesenchymal transition)
  • MARCKSL1 is a LOXL2 interacting protein (scavenger-receptor domain of LOXL2 was shown to interact with the N-terminal domain of MARCKSL1)
  • is a direct repressor of NOTCH1, and represses NOTCH1 expression in the skin to promote squamous cell carcinoma progression
  • cell & other
    REGULATION
    Other its expression is regulated in a temporal manner during fracture repair
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in metastatic breast cancer-derived cell lines
    tumoral     --over  
    in colon and esophageal cancer and may contribute to tumor progression
    tumoral     --over  
    is a frequent event in gastric carcinoma progression (
    tumoral       gain of function
    one of the most highly and specifically upregulated genes in pancreatic cancer
    tumoral     --over  
    correlated with decreased overall survival and metastasis-free survival in breast cancer patients with ERBB2-positive tumors
    Susceptibility to intracranial aneurysm
    Variant & Polymorphism SNP SNP7 showed an empirically significant association with intracranial aneurysm
    Candidate gene
    Marker
  • may be a beneficial marker for breast cancer patients that could benefit most from anti-ERBB2 therapy
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    development of anti-LOXL2 therapeutics for the treatment of metastatic breast cancer
    cancerdigestivestomach
    may be a therapeutic target for preventing and treating metastases
    cancer  
    antibody allosteric modulators of enzymatic function represent a novel useful therapeutics in oncology
    immunologyinflammatory 
    antibody allosteric modulators of enzymatic function represent a novel useful therapeutics in inflammation
    cancerdigestivepancreas
    improved response toward chemotherapy in LOXL2-silenced pancreatic cancer cells is possibly mediated by the transcription factor E2F5
    cancerskin 
    target for squamous cell carcinoma progression therapy
    ANIMAL & CELL MODELS
  • germ-line deletion of Loxl2 promotes lethality in half of newborn mice mainly associated to congenital heart defects, while Loxl2 overexpression triggers male sterility due to epididymal dysfunction caused by epithelial disorganization, fibrosis and acute inflammation