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FLASH GENE
Symbol MPO contributors: mct - updated : 28-11-2017
HGNC name myeloperoxidase
HGNC id 7218
Corresponding disease
MPOD myeloperoxidase deficiency
Location 17q22      Physical location : 56.347.216 - 56.358.296
EC.number 1.11.1.7/1.11.2.2
DNA
TYPE functioning gene
SPECIAL FEATURE
text tail to tail with LPO
STRUCTURE 11.08 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map cen - MPO - LPO - EPX - qter
Authors Sakamaki (00)
Physical map
MRPS23 17q22-q23 mitochondrial ribosomal protein S23 C14orf34 14q23.2 chromosome 14 open reading frame 34 ZNF161 17q23.3 zinc finger protein 161 SFRS1 17q21.3-q22 splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) Dlc2 17q23.2 dynein light chain 2 OR4D1 17q24.2 olfactory receptor, family 4, subfamily D, member 1 HSHPX5 17q23.2 HPX-5 LOC124538 17q23.2 similar to Olfactory receptor 4D2 EPX 17q24-q25 eosinophil peroxidase FLJ20345 17q23.2 hypothetical protein FLJ20345 LPO 17q23.1 lactoperoxidase MPO 17q22-q23.1 myeloperoxidase BZRAP1 17q22-q23 benzodiazapine receptor (peripheral) associated protein 1 SUPT4H1 17q21-q23 suppressor of Ty 4 homolog 1 (S. cerevisiae) FLJ20315 17q23.2 hypothetical protein FLJ20315 FLJ40311 17q23.2 hypothetical protein FLJ40311 MTMR4 1721.1-q23 myotubularin related protein 4 PNUTL2 17q22-q23 peanut-like 2 (Drosophila) FLJ40121 17q23.2 hypothetical protein FLJ40121 TEX14 17q22-q23 testis expressed sequence 14 RAD51C 17q22-q23 RAD51 homolog C (S. cerevisiae) PPM1E 17q23.2 protein phosphatase 1E (PP2C domain containing) TRIM37 17q22-q23 tripartite motif-containing 37 LOC348235 17q23.2 hypothetical protein LOC348235
regionally located cluster with LPO and EPO
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 - 3215 - 745 - 1991 1663499
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivepharynx    
Nervousbrain    
Reproductivemale systemprostate    Homo sapiens
Visualeye    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticerythrocyte Homo sapiens
Blood/Hematopoieticmonocyte
Blood/Hematopoieticneutrophil Homo sapiens
Lymphoid/Immunemacrophage
Reproductiveepithelial cell Homo sapiens
cell lineage
cell lines
fluid/secretion blood
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an heme protein with a calcium binding loop, as other peroxidases
  • conjugated HemoP
    mono polymer dimer
    HOMOLOGY
    Homologene
    FAMILY
  • peroxidase family
  • XPO subfamily
  • mammalian heme peroxidase (MHP) multigene family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text
  • azurophilic granules
  • primary liposomes
  • basic FUNCTION
  • involved in oxygen dependent mechanism of phagocytosis and in myeloid differentiation
  • contributes critically to O2-dependent neutrophil antimicrobial activity
  • implicated in atherosclerosis and cholesterol homeostasis
  • crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation
  • acts as a major downstream mediator of atrial fibrosis and atrial arrhythmogeneity
  • intimately involved in the pathophysiology of atrial fibrillation
  • is required for neutrophil extracellular traps (NETs) formation
  • is involved in a multitude of inflammatory processes involving oxidative modification of soluble components and cellular surfaces
  • plays a key role in promoting atherosclerosis via oxidative stress by modification of both high- and low-density lipoprotein and production of other bioactive molecules
  • MPO is unique in its capacity to oxidize chloride at physiologic pH to produce hypochlorous acid (HOCl), a potent microbicide that contributes to neutrophil-mediated host defense against infection
  • MPO, via its catalytic activity, inhibits the generation of adaptive immunity by suppressing dendritic cells (DCs) activation, Ag uptake/processing, and migration to lymph nodes (LNs) to limit pathological tissue inflammation
  • abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases
  • uses hydrogen peroxide generated by the oxidative burst of neutrophils to produce an array of antimicrobial oxidants
  • has both potent microbicidal and, upon binding to the vessel wall, pro-inflammatory properties
  • role for myeloperoxidase-dependent lipid peroxidation
  • MPO -dependent lipid peroxidation promotes the oxidative modification of cytosolic proteins in phagocytic neutrophils
  • MPO may contribute importantly to formation and rupture of cerebral aneurysms
  • important and previously unsuspected role for MPO and EPX as drivers of angiogenesis
  • chaperoned by calreticulin (CALR) in the endoplasmic reticulum
  • MPO and PRTN3 in neutrophils of Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) patients with active disease have a distinct pattern of histone modifications, which implicates epigenetic mechanisms in regulating expression of autoantigen genes
  • peroxidase enzymes, like MPO and EPX, may play a fundamental role in inhibiting TNFSF11-induced osteoclast differentiation at inflammatory sites of bone fracture and injury
  • the difference in MPO between women with abnormal and normal menstrual cycles and the upregulation of MPO before ovulation suggest that neutrophils and MPO are closely related to ovulation
  • is the major peroxidase enzyme in neutrophil granules and is implicated in contributing to inflammatory lung damage in cystic fibrosis
  • EPX and MPO are key contributors to cancer progression by augmenting pro-tumorigenic collagen production and angiogenesis
  • is synthesized by neutrophil and monocyte precursor cells and contributes to host defense by mediating microbial killing
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • formed by dimerization of hemi-MPO
  • MPO, PON1, and high-density lipoprotein bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ceruloplasmin (CP), the multicopper oxidase of plasma, interacts with myeloperoxidase (MPO), and inhibits its peroxidase and chlorinating activity
  • NR1H3 and PPARA target gene (role of these receptors in regulation of proinflammatory genes in macrophages)
  • interacting with SFTPD (myeloperoxidase-dependent inactivation of surfactant protein D)
  • CP should provide a protective shield against inadvertent oxidant production by MPO during inflammation
  • MPO binds to extracellular matrix (ECM) proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins
  • MPO binds CFP directly, which then serves as a focus for alternative pathway (AP) activation
  • SERPING1 inhibits the peroxidase activity of MPO in CF (cystic fibrosis) sputum likely via an antioxidant mechanism
  • cell & other
  • bind to both endothelial cells and leukocyte membranes
  • REGULATION
    induced by oxidative stress that induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure
    Other cleaved in an alpha large (59kDa) iron binding subunit and two smaller beta subunits (13kDa)
    ASSOCIATED DISORDERS
    corresponding disease(s) MPOD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in children with hypercholesterolemia
    tumoral       loss of function
    in myelofibrosis (MF) patients with MPO deficiency is associated a homozygous CALR mutation and also deficiency in eosinophilic peroxidase (EPX
    constitutional       gain of function
    is associated with the development of obesity
    Susceptibility
  • to Kawasaki disease (KD)
  • to gastric cancer
  • Variant & Polymorphism SNP
  • G allele of MPO -463G>A polymorphism is a potential genetic marker for KD risk
  • MPO gene polymorphism MPO-463 G/G genotype is associated with susceptibility of gastric cancer
  • Candidate gene
    Marker
  • may potentially be used as an imaging biomarker of cerebral aneurysm instability
  • is an early biomarker of inflammation associated with cardiovascular disease (CVD) risk in obese children at the prepubertal age
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    peroxidase inhibitors may have therapeutic potential for the treatment of angiogenesis related diseases driven by inflammation
    cardiovascularrythm 
    may serve as a potential new target of treatment in atrial fibrillation
    ANIMAL & CELL MODELS
  • Mpo-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored
  • Mpo deficiency upregulates the expression of several proinflammatory cytokines and chemokines in mouse neutrophils
  • in diabetic rat aortas, both Mpo expresion and NADPH oxidase activity were increased while the endothelial function was simultaneously impaired