Names & Taxonomy
- Uniprot ID:
- P08473
- Entry Name:
- NEP_HUMAN
- Status:
- reviewed
- Protein Names:
- Neprilysin (EC 3.4.24.11) (Atriopeptidase) (Common acute lymphocytic leukemia antigen) (CALLA) (Enkephalinase) (Neutral endopeptidase 24.11) (NEP) (Neutral endopeptidase) (Skin fibroblast elastase) (SFE) (CD antigen CD10)
- Gene Names:
- MME EPN
- Gene Names Primary:
- MME
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 750
- Sequence:
- MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSSDCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKDVLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGASWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYNKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILTKYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAVVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYRAYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGTLQNSAEFSEAFHCRKNSYMNPEKKCRVW
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane; Single-pass type II membrane protein.
Function
- Function:
- Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of atrial natriuretic factor (ANF) (PubMed:2531377, PubMed:2972276). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573).
- Catalytic Activity:
- Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
- Cofactor:
- COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=55.1 uM for angiotensin-1
- Enzyme Regulation:
- ENZYME REGULATION: Inhibited in a dose dependent manner by opiorphin.
- Active Site:
- ACT_SITE 585 585; ACT_SITE 651 651 Proton donor.
- Cross Reference Drug Bank:
- DB00616 DB06655 DB09292
- Gene Ontology Go:
- axon
brush border
cytoplasm
dendrite
extracellular exosome
focal adhesion
integral component of membrane
integral component of plasma membrane
neuron projection terminus
plasma membrane
synapse
synaptic vesicle
endopeptidase activity
exopeptidase activity
metalloendopeptidase activity
peptide binding
zinc ion binding
angiotensin maturation
beta-amyloid metabolic process
cellular protein metabolic process
cellular response to cytokine stimulus
cellular response to UV-A
cellular response to UV-B
creatinine metabolic process
kidney development
peptide metabolic process
proteolysis
replicative senescence
sensory perception of pain - Gene Ontology Biological Process:
- angiotensin maturation
beta-amyloid metabolic process
cellular protein metabolic process
cellular response to cytokine stimulus
cellular response to UV-A
cellular response to UV-B
creatinine metabolic process
kidney development
peptide metabolic process
proteolysis
replicative senescence
sensory perception of pain - Gene Ontology Molecular Function:
- endopeptidase activity
exopeptidase activity
metalloendopeptidase activity
peptide binding
zinc ion binding - Gene Ontology Cellular Component:
- axon
brush border
cytoplasm
dendrite
extracellular exosome
focal adhesion
integral component of membrane
integral component of plasma membrane
neuron projection terminus
plasma membrane
synapse
synaptic vesicle - Keywords:
- 3D-structure
Cell membrane
Complete proteome
Disulfide bond
Glycoprotein
Hydrolase
Lipoprotein
Membrane
Metal-binding
Metalloprotease
Myristate
Phosphoprotein
Protease
Reference proteome
Signal-anchor
Transmembrane
Transmembrane helix
Zinc - Interacts With:
- P21926; P08107; P04792