SKL (Drosophila melanogaster)
Description [+]
- Synonyms: SKL, SICKLE, IAP-INHIBITORY PROTEIN SICKLE
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: NA
- Family: IAP antagonist
- Process: apoptosis,
- Pathways:
- Criteria: manually curated
- Curator comment:
- WIKI: SKL-D_melanogaster
References [+]
- sickle, a novel Drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein.
- Srinivasula SM, Datta P, Kobayashi M, Wu JW, Fujioka M, Hegde R, Zhang Z, Mukattash R, Fernandes-Alnemri T, Shi Y, Jaynes JB, Alnemri ES
- Inhibitors of apoptosis proteins (IAPs) interact with caspases and inhibit their protease activity, whereas the IAP-inhibitory proteins Smac/DIABLO in mammals and Reaper, Hid, and Grim in flies relieve IAP-mediated inhibition to induce cell death. Here we describe the functional characterization of the novel Drosophila cell death protein Sickle (Skl), which binds to IAPs and neutralizes their apoptotic inhibitory activity. Skl exhibits no sequence homology to Reaper, Hid, Grim, or Smac/DIABLO, except within the 4 residue N-terminal IAP binding motif. Skl interacts with Drosophila and mammalian IAPs and can promote caspase activation in the presence of IAPs. Consistent with these findings, expression of Skl in Drosophila and mammalian cell lines or in Drosophila embryos induces apoptosis. Skl can also synergize with Grim to induce cell death in the Drosophila eye imaginal disc. Based on biochemical and structural data, the N terminus of Skl, like that of the mammalian Smac/DIABLO, is absolutely required for its apoptotic and caspase-promoting activities and its ability to interact with IAPs. These findings point to conservation in the structure and function of the IAP-inhibitory proteins across species and suggest the existence of other family members. Curr Biol. 2002 Jan 22;12(2):125-30.
Structure & Sequence [+]
Protein sequence [+]
skl | Drosophila melanogaster | 7227 | length:108
MAIPFFEEEHAPKSEPSGDQVDSPMAFSIDPGHDQVDFEGPPSAAEELPPPGATSEPVAP
PSAEEQLLAWKFLAITMCKVLKQFYQQHKSSGKSSKLKATVQIQPQAQ
PSAEEQLLAWKFLAITMCKVLKQFYQQHKSSGKSSKLKATVQIQPQAQ
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006616 | SRP-dependent cotranslational protein targeting to membrane, translocation | biological_proccess | ISS |
| GO:0006810 | transport | biological_proccess | IEA |
| GO:0015031 | protein transport | biological_proccess | IEA |
| GO:0065002 | intracellular protein transmembrane transport | biological_proccess | IEA |
| GO:0005488 | binding | mollecular_function | IEA |
| GO:0005783 | endoplasmic reticulum | cell_component | IEA |
| GO:0005788 | endoplasmic reticulum lumen | cell_component | IEA |
Check GO Evidence Codes here
miRNAs [+]
| miRNA | Regulation | Description | Pubmed |
|---|---|---|---|
| dme-miR-11 | downregulation by 2’-O-Me antisense miRNA oligon | Finally, the skl GFP sensor shows significant derepression for all four family mem bers (Figures 7A–7L). | Ref. |
| dme-miR-13b | downregulation by 2’-O-Me antisense miRNA oligon | Finally, the skl GFP sensor shows significant derepression for all four family mem bers (Figures 7A–7L). | Ref. |
| dme-miR-2a | overexpression by miRNA precursor transfection | The grim and sickle 39 UTR sensor transgenes were expressed at detectable levels in transgenic flies and were both downregulated by expression of miR-2b in the wing disc (Figure 4D and 4E). | Ref. |
| dme-miR-2b | downregulation by 2’-O-Me antisense miRNA oligon | Finally, the skl GFP sensor shows significant derepression for all four family mem bers (Figures 7A–7L). | Ref. |
| dme-miR-2b | overexpression by mature miRNA transfection | The second site contains a 7mer seed for miR-2 and miR-6 but only a 6mer seed for miR-11 (Figure 5C, right). miR-2 strongly downregulated the sickle reporter, miR-6 had moderate activity (presumably via the 7mer seed site), and miR-11 had nearly no activity, even though the miRNAs were overexpressed. | Ref. |
| dme-miR-308 | downregulation by 2’-O-Me antisense miRNA oligon | Finally, the skl GFP sensor shows significant derepression for all four family mem bers (Figures 7A–7L). | Ref. |
| dme-miR-6 | downregulation by 2’-O-Me antisense miRNA oligon | Finally, the skl GFP sensor shows significant derepression for all four family mem bers (Figures 7A–7L). | Ref. |
| dme-miR-6 | overexpression by mature miRNA transfection | The second site contains a 7mer seed for miR-2 and miR-6 but only a 6mer seed for miR-11 (Figure 5C, right). miR-2 strongly downregulated the sickle reporter, miR-6 had moderate activity (presumably via the 7mer seed site), and miR-11 had nearly no activity, even though the miRNAs were overexpressed. | Ref. |
Information from other databases [+]
- Gene info from FyBase [?] FBgn0036786
- Ensembl genome browser [?] : FBgn0036786
- Expression info from Arrayexpress [?] : FBgn0036786
- Protein expression from Protein Atlas: [?] FBgn0036786
Click on [?] for more information.
