IMD (Drosophila melanogaster)
Description [+]
- Synonyms: IMD, IMMUNE DEFICIENCY, BG5
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: NA
- Family: Death Domain-containing protein : other
- Process: immunity,
- Pathways:
- Criteria: manually curated
- Curator comment:
- Human ortholog(s): RIPK1
- WIKI: IMD-D_melanogaster
References [+]
- [Bleeding in haemophilia during massive treatment with anti-haemophilic globulin (author's transl)]
- Sutor AH, Jesdinsky-Buscher C
- After a traffic accident, causing intracranial haemorrhage in a 15-year-old boy with moderately severe haemophilia A, severe bleeding sequelae could not be prevented despite satisfactory substitution with lyophilized antihaemophilic globulin. The bleeding was probably due to a platelet abnormality and not due to an inhibitor. The bleedings were brought under control by freshly prepared cryoprecipitate of the patient's own blood group. Dtsch Med Wochenschr. 1975 May 23;100(21):1183-6.
- References from Human ortholog(s):
- Identification of RIP1 kinase as a specific cellular target of necrostatins.
- Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J
- Necroptosis is a cellular mechanism of necrotic cell death induced by apoptotic stimuli in the form of death domain receptor engagement by their respective ligands under conditions where apoptotic execution is prevented. Although it occurs under regulated conditions, necroptotic cell death is characterized by the same morphological features as unregulated necrotic death. Here we report that necrostatin-1, a previously identified small-molecule inhibitor of necroptosis, is a selective allosteric inhibitor of the death domain receptor-associated adaptor kinase RIP1 in vitro. We show that RIP1 is the primary cellular target responsible for the antinecroptosis activity of necrostatin-1. In addition, we show that two other necrostatins, necrostatin-3 and necrostatin-5, also target the RIP1 kinase step in the necroptosis pathway, but through mechanisms distinct from that of necrostatin-1. Overall, our data establish necrostatins as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis. Nat Chem Biol. 2008 May;4(5):313-21.
- TNF-alpha induces two distinct caspase-8 activation pathways.
- Wang L, Du F, Wang X
- The inflammatory response of mammalian cells to TNF-alpha can be switched to apoptosis either by cotreatment with a protein synthesis inhibitor, cycloheximide, or Smac mimetic, a small molecule mimic of Smac/Diablo protein. Cycloheximide promotes caspase-8 activation by eliminating endogenous caspase-8 inhibitor, c-FLIP, while Smac mimetic does so by triggering autodegradation of cIAP1 and cIAP2 (cIAP1/2), leading to the release of receptor interacting protein kinase (RIPK1) from the activated TNF receptor complex to form a caspase-8-activating complex consisting of RIPK1, FADD, and caspase-8. This process also requires the action of CYLD, a RIPK1 K63 deubiquitinating enzyme. RIPK1 is critical for caspase-8 activation-induced by Smac mimetic but dispensable for that triggered by cycloheximide. Moreover, Smac mimetic-induced caspase-8 activation is not blocked by endogenous c-FLIP. These findings revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP. Cell. 2008 May 16;133(4):693-703.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Death | 177 | 263 |
Protein sequence [+]
imd | Drosophila melanogaster | 7227 | length:273
MSKLRNLLPTIFGGKEAQNPTPVEGRLEKDAAPVDDNEPDNNNSGALALPSTAGTPTASS
DLTESVLRELSDPNYNSMDVVHSANIPGTLSNVQTNNTMNVHSAQQQVVMNFSNANNLHF
GSVYNFNQNLSACSSRKGSTSTAEESVASPDGKPRASATRKTVSIVAMMQSQEEPDVRLL
DVVSTHLGEGWKQVMRDLGMSEGQIDQAIIDHQMHGNIREVIYQLLLQWIRSSADGVATV
GRLTTLLWESQHRDCVQRMKLVWKALEKRKTNS
DLTESVLRELSDPNYNSMDVVHSANIPGTLSNVQTNNTMNVHSAQQQVVMNFSNANNLHF
GSVYNFNQNLSACSSRKGSTSTAEESVASPDGKPRASATRKTVSIVAMMQSQEEPDVRLL
DVVSTHLGEGWKQVMRDLGMSEGQIDQAIIDHQMHGNIREVIYQLLLQWIRSSADGVATV
GRLTTLLWESQHRDCVQRMKLVWKALEKRKTNS
Structure links:
- Smartdomain prediction information: SM00005
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL010083-PA | orthology | Aedes |
| IMD | orthology | Anopheles |
| RIPK1 | orthology | Chimpanzee |
| RIPK1 | orthology | Gorilla |
| RIPK1 | orthology | Human |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0008363 | larval chitin-based cuticle development | biological_proccess | NAS |
| GO:0042302 | structural constituent of cuticle | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0008010 | structural constituent of chitin-based larval cuticle | mollecular_function | NAS |
| GO:0045735 | nutrient reservoir activity | mollecular_function | IEA |
| GO:0005576 | extracellular region | cell_component | NAS |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from FyBase [?] FBgn0013983
- Ensembl genome browser [?] : FBgn0013983
- Expression info from Arrayexpress [?] : FBgn0013983
- Protein expression from Protein Atlas: [?] FBgn0013983
Click on [?] for more information.
