Q5RE69 · NEP_PONAB

Function

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.

Catalytic activity

  • Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
    EC:3.4.24.11 (UniProtKB | ENZYME | Rhea)
  • substance P + H2O = substance P(1-9) + L-Leu-L-Met-NH2
    This reaction proceeds in the forward direction.
  • substance P + H2O = substance P(1-7) + L-Phe-Gly-L-Leu-L-Met-NH2
    This reaction proceeds in the forward direction.
  • neurotensin + H2O = neurotensin(1-11) + L-isoleucyl-L-leucine
    This reaction proceeds in the forward direction.
  • neurotensin + H2O = neurotensin(1-10) + L-tyrosyl-L-isoleucyl-L-leucine
    This reaction proceeds in the forward direction.

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Features

Showing features for binding site, active site.

Type
IDPosition(s)Description
Binding site103a peptide (UniProtKB | ChEBI); substrate
Binding site584Zn2+ (UniProtKB | ChEBI); catalytic
Active site585
Binding site588Zn2+ (UniProtKB | ChEBI); catalytic
Binding site647Zn2+ (UniProtKB | ChEBI); catalytic
Active site651Proton donor

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentbrush border
Cellular Componentcytoplasm
Cellular Componentdendrite
Cellular Componentearly endosome
Cellular Componentmembrane raft
Cellular Componentneuron projection terminus
Cellular Componentneuronal cell body
Cellular Componentplasma membrane
Cellular Componentsynapse
Cellular Componentsynaptic vesicle
Cellular Componenttrans-Golgi network
Molecular Functioncardiolipin binding
Molecular Functionexopeptidase activity
Molecular Functionmetalloendopeptidase activity
Molecular Functionpeptide binding
Molecular Functionphosphatidylserine binding
Molecular Functionprotein homodimerization activity
Molecular Functionzinc ion binding
Biological Processamyloid-beta clearance by cellular catabolic process
Biological Processamyloid-beta metabolic process
Biological Processbradykinin catabolic process
Biological Processcellular response to cytokine stimulus
Biological Processcellular response to UV-A
Biological Processcellular response to UV-B
Biological Processcreatinine metabolic process
Biological Processhormone catabolic process
Biological Processkidney development
Biological Processlearning or memory
Biological Processneuropeptide processing
Biological Processpeptide metabolic process
Biological Processpositive regulation of long-term synaptic potentiation
Biological Processpositive regulation of neurogenesis
Biological Processproteolysis
Biological Processreplicative senescence
Biological Processsensory perception of pain
Biological Processsubstance P catabolic process

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Neprilysin
  • EC number
  • Alternative names
    • Atriopeptidase
    • Enkephalinase
    • Neutral endopeptidase 24.11 (NEP; Neutral endopeptidase)
    • Skin fibroblast elastase (SFE)
  • CD Antigen Name
    • CD10

Gene names

    • Name
      MME

Organism names

Accessions

  • Primary accession
    Q5RE69
  • Secondary accessions
    • Q5R5K3
    • Q5RFQ2

Proteomes

Subcellular Location

Features

Showing features for topological domain, transmembrane.

Type
IDPosition(s)Description
Topological domain2-28Cytoplasmic
Transmembrane29-51Helical; Signal-anchor for type II membrane protein
Topological domain52-750Extracellular

Keywords

PTM/Processing

Features

Showing features for initiator methionine, lipidation, chain, modified residue, disulfide bond, glycosylation.

Type
IDPosition(s)Description
Initiator methionine1Removed
Lipidation2N-myristoyl glycine
ChainPRO_00003198852-750Neprilysin
Modified residue4Phosphoserine
Modified residue6Phosphoserine
Disulfide bond57↔62
Disulfide bond80↔735
Disulfide bond88↔695
Disulfide bond143↔411
Glycosylation145N-linked (GlcNAc...) asparagine
Disulfide bond234↔242
Glycosylation285N-linked (GlcNAc...) asparagine
Glycosylation311N-linked (GlcNAc...) asparagine
Glycosylation325N-linked (GlcNAc...) asparagine
Glycosylation335N-linked (GlcNAc...) asparagine
Disulfide bond621↔747
Glycosylation628N-linked (GlcNAc...) asparagine

Post-translational modification

Myristoylation is a determinant of membrane targeting.
Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.

Keywords

PTM databases

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, motif, domain.

Type
IDPosition(s)Description
Region1-20Disordered
Motif16-23Stop-transfer sequence
Domain56-750Peptidase M13

Sequence similarities

Belongs to the peptidase M13 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    750
  • Mass (Da)
    85,514
  • Last updated
    2008-02-26 v2
  • Checksum
    C4D1216E8361352F
MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSSDCIKSAARLIQNMDATAEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKDVLQEPKTEDIVAVQKAKTLYRSCINESAIDSRGGEPLLKLLPDVYGWPVATENWEQKYGASWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYKKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILTKYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAVVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYRAYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGTLQNSAEFSEAFHCRKNSYMNPEKKCRVW

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A2J8WT72A0A2J8WT72_PONABMME80
A0A8J9E2M7A0A8J9E2M7_PONABMME749

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict115in Ref. 1; CAH89405
Sequence conflict175in Ref. 1; CAH89405
Sequence conflict523in Ref. 1; CAH89938
Sequence conflict681in Ref. 1; CAH92963
Sequence conflict729in Ref. 1; CAH92963

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
CR857100
EMBL· GenBank· DDBJ
CAH89405.1
EMBL· GenBank· DDBJ
mRNA
CR857668
EMBL· GenBank· DDBJ
CAH89938.1
EMBL· GenBank· DDBJ
mRNA
CR860855
EMBL· GenBank· DDBJ
CAH92963.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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