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FLASH GENE
Symbol LOX contributors: mct/npt/pgu - updated : 27-04-2017
HGNC name lysyl oxidase
HGNC id 6664
Location 5q23.1      Physical location : 121.398.889 - 121.414.055
Synonym name protein-lysine 6-oxidase
Synonym symbol(s) HREV142, RRG1, MGC105112
EC.number 1.4.3.13
DNA
TYPE breakpoint
STRUCTURE 15.16 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
text structure five possible binding sequences for Sp1, six for AP-2, one for AP-1, three for PEA3, three for MEP-1
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
text four minor transcripts
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 splicing 4393 21.6 187 - 2014 25017124
  • LOXv2
  • lacks exon 1 of LOX, but contains an additional 222 bp sequence from the 5prime-flanking intronic region of exon 2
  • function as amine oxidases with distinct tissue specificities
  • - splicing - 18 162 - 2010 20048148
  • lysyl oxidase propeptide
  • inhibit serum- and FGF2-stimulated DNA synthesis and FGF2-stimulated cell growth
  • may act to inhibit the proliferative response possibly to allow cells to exit from the cell cycle and progress to the next stages of osteoblasts differentiation
  • may provide a feedback control mechanism that serves to inhibit properties associated with the development of vascular pathology
  • direct interaction of LOX-PP with SH3KBP1, interaction reducing the invasive phenotype of breast cancer cells (PMID: 24167568)
  • 7 splicing 5177 46.9 417 - 2014 25017124
  • LOX
  • function as amine oxidases with distinct tissue specificities
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly Homo sapiens
    Endocrinepancreas    
    Respiratorylung    
    Skin/Tegumentskin   highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Muscularsmoothvessel highly Homo sapiens
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide 21AA
  • an active site at the C terminus including a Cu2+ binding site
  • four hystidyl residues
  • a copper-binding region
  • catalytic domain interacting with the transcription repressor GATAD2B
  • conjugated GlycoP , MetalloP
    isoforms Precursor Pro-LOX is secreted as a 50 kDa proenzyme
    HOMOLOGY
    interspecies homolog to murine Ras recision gene
    homolog to murine Lox (87.3pc)
    Homologene
    FAMILY
  • lysyl oxidase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    text extracellular matrix
    basic FUNCTION
  • lysyl oxidase, copper dependent, processed by BMP1 to the mature enzyme necessary for the formation of covalent cross-links in collagen and elastic fibers
  • playing a potential tumor suppressor role but also involved in tumor progression
  • essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases
  • key enzyme in extracellular matrix maturation
  • seems to be involved in the impairment of endothelial function triggered by different pathological conditions
  • essential for hypoxia-induced metastasis
  • its enzyme activity is critical for the biosynthesis of mature and functional collagens and elastin
  • can associate with extracellular and intracellular binding partners to affect its known biological activities as a tumor suppressor and inhibitor of cell proliferation
  • implicated in chromatin decondensation, decondensation suggested to be promoted by LOX actions on histone H1
  • essential mediator of STK11-deficiency-elicited lung cancer progression through ECM alteration, especially collagen matrix remodeling
  • may alter cancer cell growth potential via ECM remodeling
  • lysosome may regulate the dendrite development of Purkinje cells though degradation of LOX
  • multifunctional enzyme required for collagen biosynthesis
  • plays a critical role in vascular remodelling
  • critical intracellular role for LOX and LOXL2 in transcriptional regulation
  • enzyme responsible for the formation of collagen cross-links
  • PLOD1 and lysyl oxidase (LOX), contribute to ECM maturation and stabilization
  • LOX and PLOD1 are critical players in vascular calcification, and important role of ECM remodeling in this process
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • copper Cu2+
  • protein
  • interacts with EFEMP2 (importance of the ternary complex of EFEMP2, LOX, and tropoelastin in the process of elastic fiber assembly)
  • POSTN promotes the activation of LOX
  • activates AKT1 through platelet-derived growth factor receptor beta (PDGFRB) stimulation, resulting in increased VEGFA expression
  • activity participates in primary tumor growth by directly impacting the senescence stability
  • play a causal role in vascular remodeling in clinical and experimental pulmonary arterial hypertension
  • ECM cross-linking enzyme expressed in the trabecular meshwork and regulated by transforming growth factor beta (TGF-beta) isoforms
  • LOX propeptide promotes adipogenesis through inhibition of FGF2 signaling
  • EMILIN1 not only assists in EFEMP2 and tropoelastin deposition onto the fibrillin microfibril (FMF) scaffold during elastogenesis, but also targets LOX via EFEMP2 to collagen fibers in order to establish critical collagen crosslinks
  • cell & other
    REGULATION
    inhibited by TNF (endothelial dysfunction induced by TNF is associated with a decrease of LOX expression/activity)
    Other regulated by hypoxia-inducible factor (HIF)
    GATAD2B might be important for the regulation of LOX in the nucleus
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    low expressed by hypermethylation in gastric cancer
    tumoral     --over  
    elevated in hypoxic tumour cells (breast, head and neck tumors)
    constitutional     --other  
    dysregulated in pulmonary arterial hypertension
    constitutional     --low  
    in keratoconus and in keratoconus-associated disorders
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • promising biomarker for lung cancer prognosis (
  • may be a tumour endothelial cells (TECs) marker
  • Therapy target good therapeutic target for preventing and treating metastases
    SystemTypeDisorderPubmed
    cancerlung 
    potential target for disease treatment in lung cancer patients
    cancerangiogenesis 
    possible therapeutic target for novel antiangiogenic therapy
    ANIMAL & CELL MODELS