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FLASH GENE
Symbol LOX contributors: mct/npt/pgu - updated : 27-04-2015
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
  • 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