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FLASH GENE
Symbol MME contributors: mct - updated : 11-10-2016
HGNC name membrane metallo-endopeptidase
HGNC id 7154
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a single 24-amino acid hydrophobic segment that could function as both a transmembrane region and a signal peptide
  • a conserved pentapeptide zinc binding motif (HEXXH)
  • a second zinc binding motif and 10 cysteine residues
  • C-terminal 700 amino acids, including six potential N-linked glycosylation sites composing the extracellular protein segment
  • conjugated GlycoP , MetalloP
    HOMOLOGY
    Homologene
    FAMILY
  • peptidase M13 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • transmembrane glycoprotein type II
  • only the mature form of MME, which has been glycosylated in the Golgi, exists in lipid rafts, where it is directly associated with phosphatidylserine
  • basic FUNCTION
  • playing a role in regulating cerebral amyloid deposition
  • has proteolytic activity toward beta-amyloid, suggesting a possible association with Alzheimer disease
  • involved in lowering of brain APP due to plasma MME which altered blood-brain APP transport dynamics
  • fibroblastic MME expression may down-regulate skin inflammation by degrading TAC1 or reducing its level in the dermal microenvironment
  • neutral endopeptidase, that is one of the major APP-degrading enzymes in the brain
  • plays potentially a relevant role in renal embryogenesis
  • contributes to free fatty acid (FFA)-induced cellular dysfunction in nonislet tissues in type 2 diabetes
  • MME activity in the skin was elevated at early anagen, and decreased during catagen to telogen
  • plays likely an important role in regulating the hair cycle by its increased expression and activity in the follicular epithelium during early anagen
  • might be involved in the development of endometriosis due to its influence on CD44-dependent cell adhesion
  • important, previously neglected, role of MME for regulation of luminal factors in the epididymis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • protein constituent of transmembrane
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • cleaves and inactivates various neuropeptides and peptide hormones, including glucagon, enkephalins, TAC1, neurotensin, oxytocin, and bradykinin
  • APP-degrading protease neprilysin (MME) is down-regulated in normal aging and late-onset form of Alzheimer disease (LOAD)
  • estrogen stimulates degradation of APP by up-regulating MME, reducing risk for Alzheimer
  • TAC1 in pulmonary and synovial cells is degraded by MME
  • MME protected against beta cell cytotoxicity induced by exogenously added or endogenously produced human IAPP
  • major regulator of bioactivity of natriuretic peptides
  • MME up-regulation might be an adaptive response to hypoxia, which was mediated by HIF1A binding to HDAC1 at the early stage of hypoxia
  • cell & other
    REGULATION
    induced by PRKCE; specific PRKCE activation directly stimulated MME activity, leading to degradation of a monomeric form of APP peptide and decreased APP neuronal toxicity
    inhibited by PROL1
    Other developmentally regulated in other cell types, i.e. lymphocytes
    ASSOCIATED DISORDERS
    corresponding disease(s) CMT2T , SCA43
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in acute lymphoblastic leukemias
    constitutional germinal mutation      
    truncating mutations causing alloimmunisation during pregnancy and diopathic renal failure in early adulthood (might be caused by immune-mediated fetal nephron loss)
    constitutional       gain of function
    per se mediates insulin secretory dysfunction
    tumoral       loss of function
    hypoxia negatively regulates the tumor suppressor function of MME in prostate cancer
    tumoral     --low  
    in prostate cancer
    constitutional       loss of function
    reduction in MME and IDE activity is not the primary cause of APP accumulation in Alzheimer disease, but rather a late-stage phenomenon secondary to neurodegeneration
    Susceptibility to late-onset Alzheimer's disease
    Variant & Polymorphism
    Candidate gene for the development of alternative therapies for Alzheimer's disease
    Marker
  • tumoral MME expression correlated with aggressive histologic types and higher mitotic activity and is an independent prognostic factor for patients with malignant pleural mesothelioma
  • Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials
    diabete  
    interventions to inhibit neprilysin may improve beta-cell function in obese humans with type 2 diabetes
    cancerreproductiveprostate
    upregulation of MME may provide a novel therapeutic strategy in prostate cancer
    ANIMAL & CELL MODELS
  • mice deficient in neprilysin showed no obvious degenerative changes in peripheral nerves