Detail Information for IndEnz0002007816
IED ID IndEnz0002007816
Enzyme Type ID protease007816
Protein Name Neprilysin
EC 3.4.24.11
Atriopeptidase
Enkephalinase
Neutral endopeptidase 24.11
NEP
Neutral endopeptidase
Skin fibroblast elastase
SFE
CD antigen CD10
Gene Name MME
Organism Oryctolagus cuniculus (Rabbit)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Lagomorpha Leporidae (rabbits and hares) Oryctolagus Oryctolagus cuniculus (Rabbit)
Enzyme Sequence MGRSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTVIAVTMIALYATYDDGICKSSDCIKSAARLIQNMDATAEPCTDFFKYACGGWLKRNVIPETSSRYSNFDILRDELEVILKDVLQEPKTEDIVAVQKAKTLYRSCVNETAIDSRGGQPLLKLLPDVYGWPVATQNWEQTYGTSWSAEKSIAQLNSNYGKKVLINFFVGTDDKNSMNHIIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMIAVAKLIRQEEGLPIDENQISVEMNKVMELEKEIANATTKSEDRNDPMLLYNKMTLAQIQNNFSLEINGKPFSWSNFTNEIMSTVNINIPNEEDVVVYAPEYLIKLKPILTKYFPRDFQNLFSWRFIMDLVSSLSRTYKDSRNAFRKALYGTTSESATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKKAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWITGAAIVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLVDWWTQQSANNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGIGQAYRAYQNYVKKNGEEKLLPGIDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGSLQNSVEFSEAFQCPKNSYMNPEKKCRVW
Enzyme Length 750
Uniprot Accession Number P08049
Absorption
Active Site ACT_SITE 585; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233, ECO:0000255|PROSITE-ProRule:PRU10095"; ACT_SITE 651; /note="Proton donor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
Activity Regulation
Binding Site BINDING 103; /note=Substrate carboxyl; /evidence=ECO:0000250
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11; Evidence={ECO:0000250|UniProtKB:P08473};
DNA Binding
EC Number 3.4.24.11
Enzyme 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. 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. {ECO:0000250|UniProtKB:P08473}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (2); Beta strand (12); Binding site (1); Chain (1); Disulfide bond (6); Domain (1); Glycosylation (5); Helix (43); Initiator methionine (1); Lipidation (1); Metal binding (3); Modified residue (2); Motif (1); Region (1); Topological domain (2); Transmembrane (1); Turn (9)
Keywords 3D-structure;Cell membrane;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Lipoprotein;Membrane;Metal-binding;Metalloprotease;Myristate;Phosphoprotein;Protease;Reference proteome;Signal-anchor;Transmembrane;Transmembrane helix;Zinc
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein.
Modified Residue MOD_RES 4; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P08473; MOD_RES 6; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P08473
Post Translational Modification PTM: Myristoylation is a determinant of membrane targeting. {ECO:0000250}.; PTM: Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity. {ECO:0000250}.
Signal Peptide
Structure 3D X-ray crystallography (3)
Cross Reference PDB 4XBH; 4ZR5; 5V48;
Mapped Pubmed ID 31204686;
Motif MOTIF 16..23; /note=Stop-transfer sequence; /evidence=ECO:0000255
Gene Encoded By
Mass 85,582
Kinetics
Metal Binding METAL 584; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU01233; METAL 588; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU01233; METAL 647; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU01233
Rhea ID
Cross Reference Brenda