ID   NEP_PIG                 Reviewed;          26 AA.
AC   P19621;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   02-SEP-2026, entry version 101.
DE   RecName: Full=Neprilysin;
DE            EC=3.4.24.11 {ECO:0000250|UniProtKB:P08473};
DE   AltName: Full=Atriopeptidase;
DE   AltName: Full=Enkephalinase;
DE   AltName: Full=Neutral endopeptidase 24.11 {ECO:0000303|PubMed:3548708};
DE            Short=NEP;
DE            Short=Neutral endopeptidase;
DE   AltName: Full=Skin fibroblast elastase;
DE            Short=SFE;
DE   AltName: CD_antigen=CD10;
DE   Flags: Fragment;
GN   Name=MME;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Kidney;
RX   PubMed=3548708; DOI=10.1042/bj2400305;
RA   Fulcher I.S., Pappin D.J.C., Kenny A.J.;
RT   "The N-terminal amino acid sequence of pig kidney endopeptidase-24.11 shows
RT   homology with pro-sucrase-isomaltase.";
RL   Biochem. J. 240:305-308(1986).
CC   -!- FUNCTION: Thermolysin-like specificity, but is almost confined on
CC       acting on polypeptides of up to 30 amino acids. Biologically important
CC       in the destruction of opioid peptides such as Met- and Leu-enkephalins
CC       by cleavage of a Gly-Phe bond. Catalyzes cleavage of bradykinin,
CC       substance P and neurotensin peptides. Able to cleave angiotensin-1,
CC       angiotensin-2 and angiotensin 1-9. Involved in the degradation of
CC       atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-
CC       32)). Displays UV-inducible elastase activity toward skin preelastic
CC       and elastic fibers. {ECO:0000250|UniProtKB:P08473}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage of polypeptides between hydrophobic
CC         residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=substance P + H2O = substance P(1-9) + L-Leu-L-Met-NH2;
CC         Xref=Rhea:RHEA:71459, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692,
CC         ChEBI:CHEBI:190693, ChEBI:CHEBI:190700;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71460;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=substance P + H2O = substance P(1-7) + L-Phe-Gly-L-Leu-L-Met-
CC         NH2; Xref=Rhea:RHEA:71467, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692,
CC         ChEBI:CHEBI:190695, ChEBI:CHEBI:190698;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71468;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=neurotensin + H2O = neurotensin(1-11) + L-isoleucyl-L-leucine;
CC         Xref=Rhea:RHEA:71475, ChEBI:CHEBI:15377, ChEBI:CHEBI:147362,
CC         ChEBI:CHEBI:190704, ChEBI:CHEBI:190706;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71476;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=neurotensin + H2O = neurotensin(1-10) + L-tyrosyl-L-isoleucyl-
CC         L-leucine; Xref=Rhea:RHEA:71479, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:147362, ChEBI:CHEBI:190705, ChEBI:CHEBI:190707;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71480;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P08473};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P08473};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P08473};
CC       Single-pass type II membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000305}.
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DR   PIR; A26070; A26070.
DR   STRING; 9823.ENSSSCP00000057965; -.
DR   BindingDB; P19621; -.
DR   ChEMBL; CHEMBL6107; -.
DR   DrugCentral; P19621; -.
DR   PaxDb; 9823-ENSSSCP00000057965; -.
DR   eggNOG; KOG3624; Eukaryota.
DR   InParanoid; P19621; -.
DR   Proteomes; UP000008227; Unplaced.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0010815; P:bradykinin catabolic process; ISS:UniProtKB.
DR   GO; GO:0042447; P:hormone catabolic process; ISS:UniProtKB.
DR   GO; GO:0010814; P:substance P catabolic process; ISS:UniProtKB.
PE   1: Evidence at protein level;
KW   Cell membrane; Direct protein sequencing; Hydrolase; Membrane;
KW   Metalloprotease; Protease; Reference proteome; Transmembrane; Zinc.
FT   CHAIN           <1..>26
FT                   /note="Neprilysin"
FT                   /id="PRO_0000078215"
FT   NON_TER         1
FT   NON_TER         26
SQ   SEQUENCE   26 AA;  3039 MW;  3848804A9DDF7DEF CRC64;
     PKPKKKQRWT PLEISLEVLV LVLVXI
//