NEP_PIG
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 03-AUG-2022, entry version 93.
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=H2O + substance P = L-Leu-L-Met-NH2 + substance P(1-9);
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=H2O + substance P = L-Phe-Gly-L-Leu-L-Met-NH2 + substance P(1-
CC 7); 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=H2O + neurotensin = L-isoleucyl-L-leucine + neurotensin(1-11);
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=H2O + neurotensin = L-tyrosyl-L-isoleucyl-L-leucine +
CC neurotensin(1-10); 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 ChEMBL; CHEMBL6107; -.
DR DrugCentral; P19621; -.
DR PaxDb; P19621; -.
DR PRIDE; P19621; -.
DR eggNOG; KOG3624; Eukaryota.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
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
