| IED ID | IndEnz0002000949 |
| Enzyme Type ID | protease000949 |
| Protein Name |
Neprilysin-4 EC 3.4.24.11 |
| Gene Name | Nep4 CG4058 |
| Organism | Drosophila melanogaster (Fruit fly) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Protostomia Ecdysozoa Panarthropoda Arthropoda Mandibulata Pancrustacea Hexapoda Insecta Dicondylia Pterygota (winged insects) Neoptera Endopterygota Diptera Brachycera Muscomorpha Eremoneura Cyclorrhapha Schizophora Acalyptratae Ephydroidea Drosophilidae (pomace flies) Drosophilinae Drosophilini Drosophila (fruit flies) Sophophora melanogaster group melanogaster subgroup Drosophila melanogaster (Fruit fly) |
| Enzyme Sequence | MSRHSQLKLAMPSVHGAPATAPGSPMNAKARSVKLGLGVNQRTGRVQWCPGLTCCKMLLLLPVVMLPLTLVLILIMRLDGMLAALQLNEQRMRDLRNSHSEVPVYMEDYEALLPEGSTYNDLINEEFILPASKRTQLQILAAERARRCQPYRYGNGESMELEERNTLMKDSRTSFLPLGIPRECLGSGIELDIKPIDEEAYQRQKKRYQDIAPYWLEKIRIRERREAERHAEEASAEISEATAALQSFWNEEGTREGIRMTQAKTMKRYMDNKVDPCVDFYKYACGNWERLHPIPKDKAGFDTFEMLRESLDLVLRNLLEKNTPVHSAAELRKSPVRNTLFKLNEQGEGEGEADQAAELTAERLRRHIVSKRQLLNRVLVRYKRYTNGTKRKRLIETPRERTKEEEAAPPVVLPKDKTKDKSDNEEQLHVPTDFLKPHQDAQLKAKNLYRSCVNSAVLAKRGLEPLHTLIRELGGWPVLESQWSESNFNWQVLAATLRRYNNDILIVQWVGADIKNSEENIVQFDQTGLGLPTREYFLQPSNAKYLQAYQRYMAEVMHKMGASKADAQRVASELVAFETQLAGITAPAEQRLNVTKLYKRMTLDQLQAVVPEIKWRAYLQSLQDREVLGTEEVVIYAVEYMSKLVTLLDETDPRTVSNYMMWRFVRHRINNVDDRFDDIKQSFYHALFGREESPQRWKVCIAQVNTNMGMAVGSMFVSRYFDNNSKRDTLRMTHDLQQAFRDILKTTDWLDDTTKQLAEEKVNAMSLKIGYPDFILNPSELNSKYAGIEIYPEKYFENTLNVLLHTAKTEQAKLHERVNKTNWQTAPAIVNAYYSRNKNQIMFPAGILQPPFYHRHFPKSLNFGGIGVVIGHELTHGFDDKGRLFDRNGNIHKWWTDSSIRGFDERARCIIAQYSNYTVEEVGIVLNGESTQGENIADNGGLRQAFHAYQRWLKEHPSEVSDEILPGLNMTGPQLFFLNFGQVWCGAMRPEAIRNKLNTAIHSPGRFRVIGTLSNSVDFAREFNCPLGSPMNPQKKCSVW |
| Enzyme Length | 1040 |
| Uniprot Accession Number | Q8T062 |
| Absorption | |
| Active Site | ACT_SITE 873; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233, ECO:0000255|PROSITE-ProRule:PRU10095"; ACT_SITE 938; /note="Proton donor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233" |
| Activity Regulation | |
| Binding Site | |
| 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:19880729, ECO:0000269|PubMed:27919317}; |
| DNA Binding | |
| EC Number | 3.4.24.11 |
| Enzyme Function | FUNCTION: Metalloendoprotease which cleaves peptides at the amino side of hydrophobic residues - such as the hormones Akh and Dh31, and the neuropeptides Allatostatins (AST1, AST2, AST3 and AST4), Crz, Drosulfakinins (DSK-I and DSK-II), Lk, sNPF and the tachykinin peptides TK-1, TK-2, TK-4 and TK-5 (PubMed:27919317). Functions in female fertility, memory formation and may also act in regulating insulin signaling and food intake (PubMed:24395329, PubMed:27629706). Likely to be involved in controlling feeding behavior and the expression of insulin-like peptides by cleaving various regulatory peptides that include certain Drosulfakinins, Allatostatins and tachykinin peptides (PubMed:27919317). Required in females for normal patterns of egg laying and hatching (PubMed:24395329). Required in the dorsal paired medial neurons for the proper formation of long-term (LTM) and middle-term memories (MTM) (PubMed:27629706). Also required in the mushroom body neurons where it functions redundantly with neprilysins Nep2 and Nep3, in normal LTM formation (PubMed:27629706). {ECO:0000269|PubMed:24395329, ECO:0000269|PubMed:27629706, ECO:0000269|PubMed:27919317}.; FUNCTION: [Isoform A]: Cleaves angiotensin-1 and tachykinin neuropeptide substance P (PubMed:19880729). Functions in maintaining muscle integrity, possibly independently of its endopeptidase activity (PubMed:22583317). {ECO:0000269|PubMed:19880729, ECO:0000269|PubMed:22583317}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7. {ECO:0000269|PubMed:19880729}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Chain (1); Disulfide bond (4); Domain (1); Glycosylation (6); Metal binding (3); Mutagenesis (1); Region (2); Topological domain (2); Transmembrane (1) |
| Keywords | Alternative initiation;Cell membrane;Cytoplasm;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Metal-binding;Metalloprotease;Protease;Reference proteome;Sarcoplasmic reticulum;Signal-anchor;Transmembrane;Transmembrane helix;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform A]: Cell membrane {ECO:0000269|PubMed:19880729, ECO:0000269|PubMed:27919317}; Single-pass type II membrane protein {ECO:0000305}. Sarcoplasmic reticulum {ECO:0000269|PubMed:22583317}. Note=In larval muscles, localizes to both the cell surface and sarcoplasmic reticulum membranes that are continuous with the nuclear membrane. {ECO:0000269|PubMed:22583317, ECO:0000269|PubMed:27919317}.; SUBCELLULAR LOCATION: [Isoform B]: Cytoplasm {ECO:0000269|PubMed:19880729}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10961941; 11223883; 15788777; 15788778; 16934145; 18056427; 18215274; 18296030; 18463098; 20220848; 20371351; 21074052; 21684629; 23071443; 25312911; 25644700; 28213160; 28303263; 31722958; 34189422; 34556622; |
| Motif | |
| Gene Encoded By | |
| Mass | 119,577 |
| Kinetics | |
| Metal Binding | METAL 872; /note="Zinc; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 876; /note="Zinc; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 934; /note="Zinc; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01233" |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.11; |