| IED ID | IndEnz0002016066 |
| Enzyme Type ID | protease016066 |
| Protein Name |
Protein immune deficiency |
| Gene Name | imd CG5576 |
| 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 | MSKLRNLLPTIFGGKEAQNPTPVEGRLEKDAAPVDDNEPDNNNSGALALPSTAGTPTASSDLTESVLRELSDPNYNSMDVVHSANIPGTLSNVQTNNTMNVHSAQQQVVMNFSNANNLHFGSVYNFNQNLSACSSRKGSTSTAEESVASPDGKPRASATRKTVSIVAMMQSQEEPDVRLLDVVSTHLGEGWKQVMRDLGMSEGQIDQAIIDHQMHGNIREVIYQLLLQWIRSSADGVATVGRLTTLLWESQHRDCVQRMKLVWKALEKRKTNS |
| Enzyme Length | 273 |
| Uniprot Accession Number | Q7K4Z4 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Essential for the imd/NF-kappa-B (Imd) humoral and epithelial immune response to Gram-negative bacteria (PubMed:7568155, PubMed:8808632, PubMed:11266367, PubMed:12433364). Functions as an adapter protein that transduces immunity signals from the activation of pathogen recognition receptors (PRRs) by bacterial infection to the Imd signaling pathway (PubMed:7568155, PubMed:11269502, PubMed:11703941, PubMed:12433364, PubMed:20122400). Binding of diaminopimelic acid-type (DAP-type) bacterial peptidoglycans (PGN) causes multimerization or clustering of PGRP receptors which activate the Imd cascade probably by recruiting imd, Fadd and Dredd to the receptor complex (PubMed:11269502, PubMed:12433364, PubMed:20122400). Once in proximity, Dredd cleaves imd in a Fadd-dependent manner to enable its association and activation by the ubiquitin E3-ligase DIAP2 (PubMed:20122400). The activated form of imd recruits and activates the Tab2/Tak1 complex thus acting upstream of the IKK complex (ird5 and key) to activate Rel and induce the expression of antimicrobial peptides such as Def, Dpt and Cecropin (PubMed:7568155, PubMed:8808632, PubMed:11703941, PubMed:12433364, PubMed:19837371, PubMed:20122400, PubMed:11266367). Also able to inhibit the viral replication of the Sindbis virus (PubMed:19763182). Involved in promoting the polyubiquitination and stability of faf which in turn, regulates the Imd pathway by controlling imd polyubiquitination and/or stability; they may therefore form a regulatory feedback mechanism within the Imd pathway (PubMed:23919485). Not required for the cuticle melanization immune response to bacterial challenge (PubMed:11266367). {ECO:0000269|PubMed:11266367, ECO:0000269|PubMed:11269502, ECO:0000269|PubMed:11703941, ECO:0000269|PubMed:12433364, ECO:0000269|PubMed:19763182, ECO:0000269|PubMed:19837371, ECO:0000269|PubMed:20122400, ECO:0000269|PubMed:23919485, ECO:0000269|PubMed:7568155, ECO:0000269|PubMed:8808632}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (1); Compositional bias (1); Domain (1); Erroneous initiation (1); Frameshift (1); Motif (1); Mutagenesis (2); Region (4); Site (1) |
| Keywords | Immunity;Innate immunity;Reference proteome;Ubl conjugation |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | PTM: Phosphorylated. {ECO:0000269|PubMed:20122400}.; PTM: Caspase-mediated cleavage is required for activation and function; upon immune stimulation, peptidoglycans (PGN) induce proteolytic cleavage by caspases such as Dredd leading to its ubiquitination. {ECO:0000269|PubMed:20122400}.; PTM: Ubiquitination is essential for function; after PGN-induced caspase-mediated cleavage the N-terminally cleaved imd interacts with the E3 ligase Diap2 leading to polyubiquitination of 'Lys-63'-linked chains involving the E2 complex members Uev1A, ben and Ubc5 (PubMed:20122400). These 'Lys-63' chains stabilize imd and may serve as scaffolds to recruit and activate the key kinases TAK1 and IKK (PubMed:20122400). Under normal unchallenged conditions, scny deubiquitinates the activating 'Lys-63'-linked chains to prevent signal transduction and this is also likely to promote the polyubiquitination of 'Lys-48'-linked chains which act as 'tags' for proteosomal degradation (PubMed:19837371). Usp2 then deubiquitinates the 'Lys-48'-linked chains and this promotes degradation of imd probably by allowing interaction between imd and the proteasome (PubMed:25027767). {ECO:0000269|PubMed:19837371, ECO:0000269|PubMed:20122400, ECO:0000269|PubMed:25027767}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10369678; 10489372; 10602463; 10725405; 10793472; 10811906; 10898983; 10980426; 11017107; 11027343; 11050330; 11050334; 11114385; 11118328; 11156609; 11252795; 11283698; 11369236; 11418244; 11485985; 11562344; 11606746; 11724812; 11733057; 11742098; 11742378; 11823479; 11854512; 11872802; 11912488; 11912489; 11948618; 11951023; 12032070; 12123572; 12225920; 12359879; 12368087; 12401167; 12431377; 12453405; 12464174; 12513692; 12514104; 12530956; 12692550; 12728280; 12732719; 12819096; 12967553; 12967563; 14557290; 14603309; 14605208; 14731387; 15031506; 15032585; 15037551; 15199954; 15199955; 15199956; 15207846; 15221030; 15314671; 15538387; 15621522; 15640802; 15657141; 15695583; 15738385; 15771614; 15797611; 15831751; 15843462; 15894191; 16061795; 16061818; 16081424; 16163390; 16169493; 16170305; 16497588; 16767093; 16789834; 16888344; 16894030; 16940158; 17050695; 17068333; 17166233; 17194782; 17216353; 17227774; 17275304; 17343912; 17352533; 17376868; 17475494; 17509683; 17520783; 17553907; 17588928; 17603113; 17660749; 17708965; 17987029; 18039029; 18060786; 18066067; 18221416; 18248629; 18261909; 18271626; 18385808; 18390723; 18417101; 18474356; 18604211; 18654628; 18688280; 18690061; 18692774; 18820477; 18833296; 19088848; 19139277; 19218090; 19497884; 19520911; 19668222; 19716177; 19740772; 19829691; 19890048; 19893628; 19951294; 19958789; 20089584; 20137906; 20169185; 20220848; 20421637; 20457811; 20551040; 20596596; 20615957; 20627393; 20679214; 20719775; 20849943; 20865166; 20948189; 21074052; 21076039; 21148307; 21183483; 21209287; 21264297; 21270389; 21297578; 21354324; 21540243; 21641926; 21730059; 21740495; 21979942; 21987808; 22022271; 22328149; 22355724; 22368770; 22496667; 22498775; 22549468; 22611248; 22614785; 22622177; 22724070; 22772451; 22808242; 22824741; 22913798; 22949833; 23071443; 23124073; 23228366; 23261474; 23502677; 23596533; 23648644; 23663779; 23680639; 23721820; 23749869; 23764256; 23808845; 23886953; 23893105; 23986574; 24012863; 24069567; 24120681; 24127584; 24358857; 24374974; 24380076; 24381562; 24392358; 24455491; 24475130; 24628939; 24653003; 24673174; 24706930; 24733183; 24735869; 24856462; 24891502; 24907422; 24947515; 24949430; 24983497; 24997434; 25092914; 25115549; 25253354; 25281658; 25312911; 25421701; 25530181; 25533207; 25601202; 25915418; 25931442; 26068126; 26202785; 26245905; 26322507; 26374124; 26391223; 26434917; 26508789; 26513145; 26524764; 26567510; 26739560; 26859824; 26960254; 26994292; 27101844; 27152227; 27357148; 27548432; 27631699; 27819340; 27893816; 27974438; 28085885; 28102430; 28250052; 28273919; 28377500; 28445733; 28503170; 28814724; 28834743; 29045898; 29108998; 29146454; 29167272; 29522475; 29637607; 29644870; 29677000; 29693007; 29752064; 29760446; 29849035; 29915049; 29924997; 29942319; 30026495; 30119996; 30131599; 30134574; 30242153; 30344041; 30356215; 30404807; 30463009; 30633769; 30684503; 30822306; 30857831; 30902578; 30902902; 30986429; 30993906; 31009489; 31052481; 31160313; 31164352; 31167957; 31358113; 31402304; 31481676; 31575764; 31610128; 31722958; 31735669; 31835066; 31907335; 31928998; 31963772; 32019113; 32038657; 32047838; 32056841; 32174007; 32228858; 32463841; 32598400; 32598968; 32612612; 32698005; 32733472; 32774336; 32781380; 32810129; 32836177; 32866212; 32898765; 33319966; 33358662; 33377870; 33449862; 33476667; 33529757; 33573306; 33593820; 33665569; 33800390; 33828545; 33902461; 33946849; 33990202; 34341118; 34370736; 34448472; 34452932; 34463269; 8861100; 9394624; 9510254; 9529244; 9553105; 9600835; 9736738; 9826701; |
| Motif | MOTIF 31..34; /note=IAP-binding motif; /evidence=ECO:0000269|PubMed:20122400 |
| Gene Encoded By | |
| Mass | 29,899 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |