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FLASH GENE
Symbol MME contributors: mct - updated : 11-10-2016
HGNC name membrane metallo-endopeptidase
HGNC id 7154
Corresponding disease
CMT2T Charcot-Marie-Tooth disease, axonal, type 2T
SCA43 spinocerebellar ataxia 43
Location 3q25.2      Physical location : 154.797.435 - 154.901.518
Synonym name
  • antigen CD10 (gp100), 100kD identified by antibodies J5, VIL-A1, ALB2, neprilysin
  • neprilysin
  • common acute lymphoblastic leukemia antigen
  • membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase, CALLA, CD10)
  • enkephalinase
  • atriopeptidase
  • CD10 antigen
  • neutral endopeptidase 24.11
  • Synonym symbol(s) CALLA, CD10, NEP, MGC126681, MGC126707, DKFZp686O16152, EPN
    EC.number 3.4.24.11
    DNA
    TYPE functioning gene
    STRUCTURE 103.57 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    GPR105 3q21-q25 G protein-coupled receptor 105 GPR87 3q24 G protein-coupled receptor 87 GPR86 3q24 G protein-coupled receptor 86 P2RY12 3q24-q25 purinergic receptor P2Y, G-protein coupled, 12 FLJ25972 3q25.1 hypothetical protein FLJ25972 LOC344752 3q25.1 similar to Arylacetamide deacetylase LOC201651 3q25.1 similar to esterase/N-deacetylase (EC 3.5.1.-), 50K hepatic - rabbit AADAC 3q21.3-q25.2 arylacetamide deacetylase (esterase) GPR91 3q24-3q25.1 G protein-coupled receptor 91 MBNL1 3q25.1-q25.2 muscleblind-like (Drosophila) P2RY1 3q25 purinergic receptor P2Y, G-protein coupled, 1 RAP2B 3q25.2 RAP2B, member of RAS oncogene family LOC152118 3q25.2 hypothetical gene supported by AF086445 DKFZP434D146 3q25.2 DKFZP434D146 protein RH_II/GuBp2 3q25.2 similar to orphan seven transmembrane receptor DHX36 3q25 DEAH (Asp-Glu-Ala-His) box polypeptide 36 GPR149 3q25.2 G protein-coupled receptor 149 MME 3q25.1-q25.2 membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase, CALLA, CD10) LOC256283 3q25.2 hypothetical LOC256283 KIAA1069 3q26.1 hypothetical LOC256283 FLJ31139 3q25.31 hypothetical protein FLJ31139 SLC33A1 3q25.31 solute carrier family 33 (acetyl-CoA transporter), member 1 GMPS 3q24 guanine monphosphate synthetase LOC389168 3 similar to template acyivating factor-I alpha LOC344760 3q25.31 similar to seven transmembrane helix receptor MRE11B 3q25 MRE11 meiotic recombination 11 homolog B (S. cerevisiae) KCNAB1 3q26.1 potassium voltage-gated channel, shaker-related subfamily, beta member 1 SSR3 3q25.31 signal sequence receptor, gamma (translocon-associated protein gamma) TIPARP 3q25.31 TCDD-inducible poly(ADP-ribose) polymerase LOC389169 3 hypothetical gene supported by BC001951; NM_006191 LOC389170 3 similar to hypothetical protein FLJ14957 LOC339892 3q25.31 similar to Death domain containing protein CRADD (Caspase and RIP adaptator with death domain) (RIP associated protein with a death domain) CCNL1 3q26.1 cyclin L1 LOC391589 3 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) FLJ12604 3q24-q25 hypothetical protein FLJ12604 PTX3 3q21-q25 pentaxin-related gene, rapidly induced by IL-1 beta LOC152078 3q25.32 hypothetical protein BC010062 SHOX2 3q25-q26.1 short stature homeobox 2 MGC12197 3q25.32 BM-011 protein MLF1 3q25.1 myeloid leukemia factor 1 EFG1 3q25.1-q26.2 myeloid leukemia factor 1 LXN 3q25-q31 myeloid leukemia factor 1 RARRES1 3q25.31 retinoic acid receptor responder (tazarotene induced) 1 FLJ14153 3q25.32 hypothetical protein FLJ14153 GPR79 3q26 G protein-coupled receptor 79 pseudogene
    RNA
    TRANSCRIPTS type messenger
    text all transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 5643 - 750 - 2004 14968440
    also called variant 1
    23 - 5619 - 750 - 2004 14968440
    also called variant 1bis
    23 - 5710 - 750 - 2004 14968440
    also called variant 2b
    23 - 5665 - 750 - 2004 14968440
    also called variant 2A
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    Reproductivemale systemmale genital tractepididymis highly Homo sapiens
     male systemprostate  highly Homo sapiens
    Urinarykidney   highly Homo sapiensFetal
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Nervousperipherous    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    Reproductiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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