Neprilysin

MME
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DMT, 1R1H, 1R1I, 1R1J, 1Y8J, 2QPJ, 2YB9, 4CTH, 5JMY
Identifiers
Aliases	MME, CALLA, CD10, NEP, SFE, membrane metallo-endopeptidase, membrane metalloendopeptidase, CMT2T, SCA43
External IDs	OMIM: 120520; MGI: 97004; HomoloGene: 5275; GeneCards: MME; OMA:MME - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q25.2 Start 155,024,124 bp[1] End 155,183,704 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 E1|3 29.97 cM Start 63,148,958 bp[2] End 63,293,451 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa glomerulus metanephric glomerulus stromal cell of endometrium duodenum kidney tubule sural nerve human kidney mucosa of ileum blood Top expressed in epithelium of lens molar vestibular sensory epithelium prostate Gonadal ridge lobe of prostate vestibular membrane of cochlear duct external carotid artery calvaria vas deferens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding zinc ion binding exopeptidase activity hydrolase activity endopeptidase activity metal ion binding peptidase activity peptide binding metalloendopeptidase activity metallopeptidase activity phosphatidylserine binding protein homodimerization activity oligopeptidase activity cardiolipin binding Cellular component brush border focal adhesion integral component of plasma membrane cytoplasm membrane extracellular exosome integral component of membrane synaptic vesicle plasma membrane synapse axon dendrite neuron projection terminus secretory granule membrane early endosome trans-Golgi network cell surface cytoplasmic vesicle neuronal cell body membrane raft presynapse Biological process angiotensin maturation cellular response to UV-B cellular response to cytokine stimulus kidney development replicative senescence cellular response to UV-A creatinine metabolic process peptide metabolic process amyloid-beta metabolic process proteolysis sensory perception of pain neutrophil degranulation placenta development human ageing learning or memory lung development positive regulation of neurogenesis neuropeptide processing amyloid-beta clearance amyloid-beta clearance by cellular catabolic process positive regulation of long-term synaptic potentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4311 17380 Ensembl ENSG00000196549 ENSMUSG00000027820 UniProt P08473 Q3KQS6 Q61391 RefSeq (mRNA) NM_000902 NM_007287 NM_007288 NM_007289 NM_001354642 NM_001354643 NM_001354644 NM_008604 NM_001289462 NM_001289463 NM_001357335 RefSeq (protein) NP_000893 NP_009218 NP_009219 NP_009220 NP_001341571 NP_001341572 NP_001341573 NP_001276391 NP_001276392 NP_032630 NP_001344264 Location (UCSC) Chr 3: 155.02 – 155.18 Mb Chr 3: 63.15 – 63.29 Mb PubMed search [3] [4]
Wikidata
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Neprilysin (/ˌnɛprɪˈlaɪsɪn/; also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10) and common acute lymphoblastic leukemia antigen (CALLA)) is an enzyme that in humans is encoded by the MME gene. Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin.^[5] It also degrades the amyloid beta peptide whose abnormal folding and aggregation in neural tissue has been implicated as a cause of Alzheimer's disease. Synthesized as a membrane-bound protein, the neprilysin ectodomain is released into the extracellular domain after it has been transported from the Golgi apparatus to the cell surface.

Neprilysin is expressed in a wide variety of tissues and is particularly abundant in kidney. It is also a common acute lymphocytic leukemia antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). This protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL.^[5]

Hematopoietic progenitors expressing CD10 are considered "common lymphoid progenitors", which means they can differentiate into T, B or natural killer cells.^[6] CD10 is of use in hematological diagnosis since it is expressed by early B, pro-B and pre-B lymphocytes, and by lymph node germinal centers.^[7] Hematologic diseases in which it is positive include ALL, angioimmunoblastic T cell lymphoma, Burkitt lymphoma, chronic myelogenous leukemia in blast crisis (90%), diffuse large B-cell lymphoma (variable), follicular center cells (70%), hairy cell leukemia (10%), and myeloma (some). It tends to be negative in acute myeloid leukemia, chronic lymphocytic leukemia, mantle cell lymphoma, and marginal zone lymphoma. CD10 is found on non-T ALL cells, which derive from pre-B lymphocytes, and in germinal center-related non-Hodgkin lymphoma such as Burkitt lymphoma and follicular lymphoma, but not on leukemia cells or lymphomas, which originate in more mature B cells.^[8]