| IED ID | IndEnz0002000956 |
| Enzyme Type ID | protease000956 |
| Protein Name |
Neprilysin EC 3.4.24.11 Atriopeptidase Common acute lymphocytic leukemia antigen CALLA Enkephalinase Neutral endopeptidase 24.11 NEP Neutral endopeptidase Skin fibroblast elastase SFE CD antigen CD10 |
| Gene Name | MME EPN |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSSDCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKDVLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGASWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYNKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILTKYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAVVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYRAYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGTLQNSAEFSEAFHCRKNSYMNPEKKCRVW |
| Enzyme Length | 750 |
| Uniprot Accession Number | P08473 |
| 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, ECO:0000269|PubMed:8168535" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited in a dose dependent manner by opiorphin (PubMed:17101991). Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059). {ECO:0000269|PubMed:17101991, ECO:0000269|PubMed:26931059}. |
| 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:0000269|PubMed:15283675, ECO:0000269|PubMed:27588448, ECO:0000269|PubMed:8168535}; |
| 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 (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)) (PubMed:2531377, PubMed:2972276, PubMed:16254193). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573). {ECO:0000269|PubMed:15283675, ECO:0000269|PubMed:17101991, ECO:0000269|PubMed:20876573, ECO:0000269|PubMed:2531377, ECO:0000269|PubMed:27588448, ECO:0000269|PubMed:2972276}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Beta strand (15); Binding site (1); Chain (1); Disulfide bond (6); Domain (1); Erroneous initiation (1); Glycosylation (4); Helix (42); Initiator methionine (1); Lipidation (1); Metal binding (3); Modified residue (2); Motif (1); Natural variant (8); Region (1); Sequence conflict (4); Topological domain (2); Transmembrane (1); Turn (8) |
| Keywords | 3D-structure;Cell membrane;Charcot-Marie-Tooth disease;Disease variant;Disulfide bond;Glycoprotein;Hydrolase;Lipoprotein;Membrane;Metal-binding;Metalloprotease;Myristate;Neurodegeneration;Neuropathy;Phosphoprotein;Protease;Reference proteome;Signal-anchor;Spinocerebellar ataxia;Transmembrane;Transmembrane helix;Zinc |
| Interact With | P05067; P21926; Q06787-7; P08107; P04792 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein. |
| Modified Residue | MOD_RES 4; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:24275569; MOD_RES 6; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:24275569 |
| Post Translational Modification | PTM: Myristoylation is a determinant of membrane targeting. {ECO:0000269|PubMed:19756956}.; PTM: Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity. {ECO:0000269|PubMed:10669592, ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14747736, ECO:0000269|PubMed:17704566, ECO:0000269|PubMed:22766194}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (16) |
| Cross Reference PDB | 1DMT; 1R1H; 1R1I; 1R1J; 1Y8J; 2QPJ; 2YB9; 4CTH; 5JMY; 6GID; 6SH1; 6SH2; 6SUK; 6SVY; 6THP; 6XVP; |
| Mapped Pubmed ID | 10439449; 10994648; 11140838; 11849775; 11906289; 12070597; 12087466; 12102663; 12105192; 12140380; 12150966; 12203213; 12387451; 12393702; 12447961; 12485446; 12527400; 12657655; 12754344; 12785004; 14550292; 14673956; 14739539; 14749444; 14767532; 14968440; 15047060; 15205682; 15217945; 15286660; 15294904; 15464186; 15469471; 15502805; 15548496; 15578072; 15720419; 15785408; 15860464; 15870909; 15945081; 16123216; 16226260; 16400325; 16652149; 16700740; 16722930; 16857799; 16877296; 16900210; 16900384; 16940054; 16943769; 16948517; 17207277; 17220478; 17294442; 17296585; 17335564; 17342744; 17363457; 17591969; 17662271; 17712175; 17845760; 17876294; 17885484; 17906676; 17928142; 17953966; 18042078; 18092952; 18182043; 18292286; 18370954; 18393807; 18518902; 18539150; 18602473; 18605079; 18619643; 18806483; 19019493; 19047112; 19057576; 19127446; 19152193; 19196432; 19250583; 19287335; 19326964; 19437324; 19448593; 19515046; 19575892; 19606063; 19656156; 19661328; 19752720; 19787248; 19816087; 19817893; 19864659; 19897485; 19925052; 19948975; 19961253; 20014550; 20051779; 20051780; 20061637; 20079015; 20105452; 20175824; 20184665; 20204382; 20376800; 20390424; 20459800; 20468064; 20506111; 20546336; 20574156; 20663017; 20685603; 20711432; 20716621; 20856894; 20886092; 20947507; 20957047; 21052031; 21076839; 21225496; 21315759; 21365649; 21425402; 21499231; 21515054; 21585282; 21609487; 21651905; 21677537; 21681600; 21775056; 21804528; 21835428; 21877416; 21883368; 21988858; 21989348; 22006372; 22014058; 2201681; 22183801; 22257901; 22272689; 22286396; 22300665; 22371247; 22384224; 22410801; 22417750; 22464152; 22492182; 22572771; 22767595; 22880404; 22898766; 22994707; 23063927; 23065018; 23138928; 23219141; 23289620; 23339695; 23348903; 23356903; 23360525; 23509938; 23566254; 23650620; 23653392; 23686701; 23752268; 23827863; 23838604; 23857215; 23863409; 24040464; 24099862; 24460801; 24603459; 24754336; 24825898; 24848988; 24874475; 24895167; 24972738; 25089527; 25125048; 25279712; 25282623; 25308002; 25452160; 25608772; 25713420; 25733581; 25759539; 25921112; 26124315; 26362309; 26414904; 26562027; 26573127; 26609034; 26830028; 26846903; 26881775; 27039776; 27096746; 27302413; 2736261; 27513891; 27616053; 27641335; 28294061; 28553432; 28628241; 29056123; 29196110; 29306324; 29323711; 29330223; 29367254; 29561187; 29653092; 29791034; 29854824; 29906506; 30249887; 30251808; 30415211; 30711939; 30796257; 30828920; 31054987; 31189595; 31266021; 31383639; 31514225; 31816181; 32012940; 32070494; 32071687; 32272124; 32337993; 32364682; 32427034; 32545905; 32762650; 32967374; 32987038; 33131987; 33144514; 33244333; 33314757; 33342805; 33393317; 33406387; 33444077; 33541392; 33608777; 34341253; 34502327; 34505762; 34507663; 34831146; 8687431; 9232196; 9857225; |
| Motif | MOTIF 16..23; /note=Stop-transfer sequence; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 85,514 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=55.1 uM for angiotensin-1 {ECO:0000269|PubMed:15283675}; KM=179 uM for angiotensin-2 {ECO:0000269|PubMed:15283675}; KM=111.4 uM for angiotensin 1-9 {ECO:0000269|PubMed:15283675}; |
| 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 | 3.4.24.11; |