Q5RE69 · NEP_PONAB
- ProteinNeprilysin
- GeneMME
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids750 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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
- substance P + H2O = substance P(1-9) + L-Leu-L-Met-NH2This reaction proceeds in the forward direction.
- substance P + H2O = substance P(1-7) + L-Phe-Gly-L-Leu-L-Met-NH2This reaction proceeds in the forward direction.
- neurotensin + H2O = neurotensin(1-11) + L-isoleucyl-L-leucineThis reaction proceeds in the forward direction.
- neurotensin + H2O = neurotensin(1-10) + L-tyrosyl-L-isoleucyl-L-leucineThis reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 103 | a peptide (UniProtKB | ChEBI); substrate | |||
Binding site | 584 | Zn2+ (UniProtKB | ChEBI); catalytic | |||
Active site | 585 | ||||
Binding site | 588 | Zn2+ (UniProtKB | ChEBI); catalytic | |||
Binding site | 647 | Zn2+ (UniProtKB | ChEBI); catalytic | |||
Active site | 651 | Proton donor | |||
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameNeprilysin
- EC number
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Pongo
Accessions
- Primary accessionQ5RE69
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type II membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Topological domain | 2-28 | Cytoplasmic | |||
Transmembrane | 29-51 | Helical; Signal-anchor for type II membrane protein | |||
Topological domain | 52-750 | Extracellular | |||
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, modified residue, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Initiator methionine | 1 | Removed | |||
Lipidation | 2 | N-myristoyl glycine | |||
Chain | PRO_0000319885 | 2-750 | Neprilysin | ||
Modified residue | 4 | Phosphoserine | |||
Modified residue | 6 | Phosphoserine | |||
Disulfide bond | 57↔62 | ||||
Disulfide bond | 80↔735 | ||||
Disulfide bond | 88↔695 | ||||
Disulfide bond | 143↔411 | ||||
Glycosylation | 145 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 234↔242 | ||||
Glycosylation | 285 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 311 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 325 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 335 | N-linked (GlcNAc...) asparagine | |||
Disulfide bond | 621↔747 | ||||
Glycosylation | 628 | N-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
PTM databases
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif, domain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-20 | Disordered | |||
Motif | 16-23 | Stop-transfer sequence | |||
Domain | 56-750 | Peptidase M13 | |||
Sequence similarities
Belongs to the peptidase M13 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length750
- Mass (Da)85,514
- Last updated2008-02-26 v2
- ChecksumC4D1216E8361352F
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2J8WT72 | A0A2J8WT72_PONAB | MME | 80 | ||
A0A8J9E2M7 | A0A8J9E2M7_PONAB | MME | 749 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Sequence conflict | 115 | in Ref. 1; CAH89405 | |||
Sequence conflict | 175 | in Ref. 1; CAH89405 | |||
Sequence conflict | 523 | in Ref. 1; CAH89938 | |||
Sequence conflict | 681 | in Ref. 1; CAH92963 | |||
Sequence conflict | 729 | in Ref. 1; CAH92963 | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |