Neprilysin

Function

Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Catalyzes cleavage of bradykinin, substance P and neurotensin peptides. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.

Classification

Family (Pfam)

PF01431 Peptidase_M13, PF05649 Peptidase_M13_N

InterPro

MetalloPept_cat_dom_sf, Peptidase_M13, Peptidase_M13_C, Peptidase_M13_dom_2, Peptidase_M13_N

Functional cluster

Secreted Hydrolases & Toxins

Experimental structures · PDB · 16

• 1DMT X-ray 2.10A
• 1R1H X-ray 1.95A
• 1R1I X-ray 2.60A
• 1R1J X-ray 2.35A
• 1Y8J X-ray 2.25A
• 2QPJ X-ray 2.05A
• 2YB9 X-ray 2.40A
• 4CTH X-ray 2.15A
• 5JMY X-ray 2.00A
• 6GID X-ray 1.90A
• 6SH1 X-ray 2.10A
• 6SH2 X-ray 2.60A
• … and 4 more

A predicted model is available from AlphaFold.

Gene Ontology · 54

• GO:0030424 axon
• GO:0005903 brush border
• GO:0009986 cell surface
• GO:0005737 cytoplasm
• GO:0031410 cytoplasmic vesicle
• GO:0030425 dendrite
• GO:0005769 early endosome
• GO:0070062 extracellular exosome
• GO:0005925 focal adhesion
• GO:0016020 membrane
• GO:0045121 membrane raft
• GO:0044306 neuron projection terminus
• GO:0043025 neuronal cell body
• GO:0005886 plasma membrane
• GO:0098793 presynapse
• GO:0030667 secretory granule membrane
• GO:0045202 synapse
• GO:0008021 synaptic vesicle
• GO:0005802 trans-Golgi network
• GO:1901612 cardiolipin binding
• GO:0004175 endopeptidase activity
• GO:0008238 exopeptidase activity
• GO:0004181 metallocarboxypeptidase activity
• GO:0004222 metalloendopeptidase activity
• GO:0070012 oligopeptidase activity
• GO:0042277 peptide binding
• GO:0001786 phosphatidylserine binding
• GO:0042803 protein homodimerization activity
• GO:0008270 zinc ion binding
• GO:0097242 amyloid-beta clearance
• GO:0150094 amyloid-beta clearance by cellular catabolic process
• GO:0050435 amyloid-beta metabolic process
• GO:0002003 angiotensin maturation
• GO:0010815 bradykinin catabolic process
• GO:0071345 cellular response to cytokine stimulus
• GO:0071492 cellular response to UV-A
• GO:0071493 cellular response to UV-B
• GO:0046449 creatinine metabolic process
• GO:0042447 hormone catabolic process
• GO:0001822 kidney development
• GO:0007611 learning or memory
• GO:0030324 lung development
• GO:0061837 neuropeptide processing
• GO:0006518 peptide metabolic process
• GO:0001890 placenta development
• GO:1900273 positive regulation of long-term synaptic potentiation
• GO:0050769 positive regulation of neurogenesis
• GO:0030163 protein catabolic process
• GO:0016485 protein processing
• GO:0006508 proteolysis
• GO:0090399 replicative senescence
• GO:0043627 response to estrogen
• GO:0019233 sensory perception of pain
• GO:0010814 substance P catabolic process

Disease associations

• Charcot-Marie-Tooth disease type 2T MONDO:0044640
• spinocerebellar ataxia 43 MONDO:0014867

Drugs targeting this protein · 4

• RACECADOTRIL inhibitor
• SACUBITRIL inhibitor
• ILEPATRIL inhibitor
• DAGLUTRIL inhibitor

Related proteins · sequence + function similarity

• Neprilysin 1.00
• Neprilysin 1.00
• Neprilysin 1.00
• Neprilysin 0.99
• Neprilysin-3 0.94
• Endothelin-converting enzyme homolog 0.94
• Neprilysin-2 0.94
• Endothelin-converting enzyme 1 0.93
• Neprilysin-1 0.93
• Neprilysin-11 0.92
• Neprilysin-2 0.91
• Endothelin-converting enzyme 1 0.90

Co-cited proteins · studied together in the literature

• Neprilysin 2 shared papers
• Opiorphin prepropeptide 1 shared papers
• Endothelin-converting enzyme 1 2 shared papers
• Natriuretic peptides A 2 shared papers
• Basic phospholipase A2 homolog 2 2 shared papers
• Angiotensinogen 1 shared papers
• Neurotensin/neuromedin N 1 shared papers
• Protachykinin-1 1 shared papers
• Natriuretic peptides B 1 shared papers
• Dipeptidyl peptidase 4 1 shared papers
• Angiotensin-converting enzyme 1 shared papers

Literature · 27 cited papers

• Rare variants in MME, encoding metalloprotease neprilysin, are linked to late-onset autosomal-dominant axonal polyneuropathies. Am. J. Hum. Genet. · 2016
• MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43). Neurol. Genet. · 2016
• Corrigendum: N-terminal domain of Bothrops asper Myotoxin II enhances the activity of endothelin converting enzyme-1 and neprilysin. Sci. Rep. · 2016
• Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2. Ann. Neurol. · 2016
• N-terminal domain of Bothrops asper Myotoxin II enhances the activity of endothelin converting enzyme-1 and neprilysin. Sci. Rep. · 2016
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• The human CD10 lacking an N-glycan at Asn(628) is deficient in surface expression and neutral endopeptidase activity. Biochim. Biophys. Acta · 2012
• Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses. J. Biol. Chem. · 2010
• Neutral endopeptidase is a myristoylated protein. Mol. Cell. Biochem. · 2010
• Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV. Acta Crystallogr. D · 2007
• Human opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc. Natl. Acad. Sci. U.S.A. · 2006
• Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form. Clin. Chem. · 2006
• … and 15 more in the literature graph