Detail Information for IndEnz0002000949
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;