ATG18 (Drosophila melanogaster)
Description [+]
- Synonyms: ATG18
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: Autophagy-specific gene 18
- Family: other
- Process: cell death (other),
- Pathways:
- Criteria: manually curated
- Curator comment: This protein participates in autophagic cell death during Drosophila development.
- Human ortholog(s): WIPI2
- WIKI: ATG18-D_melanogaster
References [+]
- Autophagy, not apoptosis, is essential for midgut cell death in Drosophila.
- Denton D, Shravage B, Simin R, Mills K, Berry DL, Baehrecke EH, Kumar S
- Most developmentally programmed cell death in metazoans is mediated by caspases. During Drosophila metamorphosis, obsolete tissues, including the midgut and salivary glands, are removed by programmed cell death [1]. The initiator caspase Dronc and its activator Ark are required for the death of salivary glands, but not for midgut removal [2, 3]. In addition to caspases, complete removal of salivary glands requires autophagy [4]. However, the contribution of autophagy to midgut cell death has not been explored. Examination of combined mutants of the main initiator and effector caspases revealed that the canonical apoptotic pathway is not required for midgut cell death. Further analyses revealed that the caspase Decay is responsible for most of the caspase activity in dying midguts, yet inhibition of this activity has no effect on midgut removal. By contrast, midgut degradation was severely delayed by inhibition of autophagy, and this occurred without a decrease in caspase activity. Surprisingly, the combined inhibition of caspases and autophagy did not result in an additional delay in midgut removal. Together, our results indicate that autophagy, not caspases, is essential for midgut programmed cell death, providing the first in vivo evidence of caspase-independent programmed cell death that requires autophagy despite the presence of high caspase activity. Curr Biol. 2009 Nov 3;19(20):1741-6. Epub 2009 Oct 8.
- Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila.
- Berry DL, Baehrecke EH
- Autophagy is a catabolic process that is negatively regulated by growth and has been implicated in cell death. We find that autophagy is induced following growth arrest and precedes developmental autophagic cell death of Drosophila salivary glands. Maintaining growth by expression of either activated Ras or positive regulators of the class I phosphoinositide 3-kinase (PI3K) pathway inhibits autophagy and blocks salivary gland cell degradation. Developmental degradation of salivary glands is also inhibited in autophagy gene (atg) mutants. Caspases are active in PI3K-expressing and atg mutant salivary glands, and combined inhibition of both autophagy and caspases increases suppression of gland degradation. Further, induction of autophagy is sufficient to induce premature cell death in a caspase-independent manner. Our results provide in vivo evidence that growth arrest, autophagy, and atg genes are required for physiological autophagic cell death and that multiple degradation pathways cooperate in the efficient clearance of cells during development. Cell. 2007 Dec 14;131(6):1137-48.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | WD40 | 174 | 212 |
| PFAM A | WD40 | 174 | 212 |
Protein sequence [+]
Atg18 | Drosophila melanogaster | 7227 | length:377
MMSLLGRTDVDAGEVFVNFNQNITSLAVATSGGYSLYSLGSVDSTLDKIYHTKSDELFLI
ERLFESSLVAIVSQRAPRKLKVCHFKKQSEICNYSYANTILAVKLNRERLIVCLEESLYI
HNIQDMKVVHTIRDTPCNPQGLCALSSSSEHCYLAYPGSVTAGEVQIFDAINLHAKTMIP
AHDTPLAALAFSPSGTEIATASERGTVIRVFSSQDGSRLFELRRGLKRCVSIVSLSFSTC
AEYLVSSSNTETVHIFRLDRSATETAEGHGSKQSSDDWMGYSFFRFLSKTVTSYLPTQVT
DVFSQGRAFASVTLPEAGVRRMCAIATIQKQLRLLIASQDGYLYVYSIPTVEGAECQLIK
RHDLRLEDHYAMDIKGA
ERLFESSLVAIVSQRAPRKLKVCHFKKQSEICNYSYANTILAVKLNRERLIVCLEESLYI
HNIQDMKVVHTIRDTPCNPQGLCALSSSSEHCYLAYPGSVTAGEVQIFDAINLHAKTMIP
AHDTPLAALAFSPSGTEIATASERGTVIRVFSSQDGSRLFELRRGLKRCVSIVSLSFSTC
AEYLVSSSNTETVHIFRLDRSATETAEGHGSKQSSDDWMGYSFFRFLSKTVTSYLPTQVT
DVFSQGRAFASVTLPEAGVRRMCAIATIQKQLRLLIASQDGYLYVYSIPTVEGAECQLIK
RHDLRLEDHYAMDIKGA
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL013995-PA | orthology | Aedes |
| A_gambiae_AGAP005910-PA | orthology | Anopheles |
| WIPI2_CHICK | orthology | Chicken |
| WIPI2 | orthology | Chimpanzee |
| NA | orthology | Ciona |
| NP_001039594.1 | orthology | Cow |
| WIPI2 | orthology | Dog |
| WIPI2 | orthology | Fugu |
| WIPI2 | orthology | Gasterosteus |
| WIPI2 | orthology | Gorilla |
| WIPI2 | orthology | Horse |
| WIPI2 | orthology | Human |
| WIPI2 | orthology | Lyzard |
| WIPI2 | orthology | Macaca |
| WIPI2 | orthology | Medaka |
| M_domestica_ENSMODP00000002361 | orthology | Monodelphis |
| M_domestica_ENSMODP00000034018 | orthology | Monodelphis |
| XM_001363196.1 | orthology | Monodelphis |
| Wipi2 | orthology | Mouse |
| WIPI2 | orthology | Orangutan |
| WIPI2 | orthology | Ornithorhynchus |
| WIPI2 | orthology | Rabbit |
| WIPI2_RAT | orthology | Rat |
| atg-18 | orthology | Worm |
| X_tropicalis_ENSXETP00000056956 | orthology | Xenopus |
| ATG18 | orthology | Yeast |
| ATG21 | orthology | Yeast |
| WIPI2 | orthology | Zebra finch |
| wipi2 | orthology | Zebrafish |
| A_aegypti_AAEL010791-PA | paralogy | Aedes |
| A_aegypti_AAEL013063-PA | paralogy | Aedes |
| A_gambiae_AGAP007970-PA | paralogy | Anopheles |
| A_gambiae_AGAP012792-PA | paralogy | Anopheles |
| WIPI3_CHICK | paralogy | Chicken |
| IPI00575905.2 | paralogy | Chicken |
| WIPI1 | paralogy | Chimpanzee |
| WDR45L | paralogy | Chimpanzee |
| WDR45 | paralogy | Chimpanzee |
| NA | paralogy | Ciona |
| NA | paralogy | Ciona |
| NP_001069619.1 | paralogy | Cow |
| NP_001068715.1 | paralogy | Cow |
| WIPI1 | paralogy | Cow |
| WIPI1 | paralogy | Dog |
| WDR45L | paralogy | Dog |
| WDR45 | paralogy | Dog |
| CG11975 | paralogy | Fly |
| CG8678 | paralogy | Fly |
| WDR45L | paralogy | Fugu |
| WIPI1 (2 of 2) | paralogy | Fugu |
| WIPI1 (1 of 2) | paralogy | Fugu |
| WDR45 | paralogy | Fugu |
| WIPI1 (1 of 2) | paralogy | Gasterosteus |
| WIPI1 (2 of 2) | paralogy | Gasterosteus |
| WDR45L | paralogy | Gasterosteus |
| WDR45 | paralogy | Gasterosteus |
| WDR45 | paralogy | Gorilla |
| WIPI1 | paralogy | Gorilla |
| WDR45L | paralogy | Gorilla |
| WIPI1 | paralogy | Horse |
| WDR45 | paralogy | Horse |
| WDR45L | paralogy | Horse |
| WIPI1 | paralogy | Human |
| WDR45 | paralogy | Human |
| WDR45L | paralogy | Human |
| WIPI1 | paralogy | Lyzard |
| WDR45 | paralogy | Lyzard |
| WDR45L | paralogy | Lyzard |
| WIPI1 | paralogy | Macaca |
| WDR45L | paralogy | Macaca |
| WDR45 | paralogy | Macaca |
| WDR45 | paralogy | Medaka |
| WIPI1 (1 of 2) | paralogy | Medaka |
| WDR45L | paralogy | Medaka |
| WIPI1 (2 of 2) | paralogy | Medaka |
| WDR45L | paralogy | Monodelphis |
| WIPI1 | paralogy | Monodelphis |
| Wdr45l | paralogy | Mouse |
| Wdr45 | paralogy | Mouse |
| Wipi1 | paralogy | Mouse |
| P_pygmaeus_ENSPPYP00000009167 | paralogy | Orangutan |
| WIPI1 | paralogy | Orangutan |
| WIPI3_PONPY | paralogy | Orangutan |
| WDR45L | paralogy | Ornithorhynchus |
| WDR45L | paralogy | Rabbit |
| WIPI1 | paralogy | Rabbit |
| NP_001120769.1 | paralogy | Rat |
| Wdr45 | paralogy | Rat |
| NP_001034676.1 | paralogy | Rat |
| WDR45L | paralogy | Tetraodon |
| WIPI1 (1 of 2) | paralogy | Tetraodon |
| WDR45 | paralogy | Tetraodon |
| NP_001022835.1 | paralogy | Worm |
| BC087784.1 | paralogy | Xenopus |
| wdr45 | paralogy | Xenopus |
| wdr45l | paralogy | Xenopus |
| HSV2 | paralogy | Yeast |
| WIPI1 | paralogy | Zebra finch |
| WDR45L | paralogy | Zebra finch |
| wdr45l | paralogy | Zebrafish |
| WIPI1 (2 of 2) | paralogy | Zebrafish |
| wipi1 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000090051 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0008152 | metabolic process | biological_proccess | IEA |
| GO:0016740 | transferase activity | mollecular_function | IEA |
| GO:0016757 | transferase activity, transferring glycosyl groups | mollecular_function | IEA |
| GO:0016758 | transferase activity, transferring hexosyl groups | mollecular_function | IEA |
| GO:0015020 | glucuronosyltransferase activity | mollecular_function | IEA |
| GO:0003851 | 2-hydroxyacylsphingosine 1-beta-galactosyltransferase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
Check GO Evidence Codes here
Information from other databases [+]
- Ensembl genome browser [?] : FBgn0035850
- Expression info from Arrayexpress [?] : FBgn0035850
- Protein expression from Protein Atlas: [?] FBgn0035850
Click on [?] for more information.
