DEPDC5/Iml1 GATOR1 subunit that suppresses TORC1 to control meiotic entry and oocyte development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0010508
positive regulation of autophagy
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: Iml1 supports autophagy during nutrient stress via TORC1 inhibition.
Reason: UniProt notes GATOR1 promotes survival under starvation by promoting autophagy.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
promoting survival during amino acid or complete starvation by inhibiting TORC1-dependent cell growth and promoting catabolic metabolism and autophagy
|
|
GO:0034198
cellular response to amino acid starvation
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Iml1 participates in the response to amino-acid starvation via GATOR1.
Reason: GATOR1 inhibition of TORC1 is central to the amino-acid starvation response.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
|
|
GO:1904262
negative regulation of TORC1 signaling
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
Reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing branch of TORC1.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
|
|
GO:0005765
lysosomal membrane
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: Lysosomal membrane association is consistent with GATOR localization at lysosomes.
Reason: GATOR complex functions at the lysosome in nutrient sensing; Iml1 is a GATOR1 subunit.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3
|
|
GO:1990130
GATOR1 complex
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Iml1 is a core subunit of the GATOR1 complex.
Reason: UniProt annotates Iml1 as a probable GATOR1 subcomplex component.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3
file:genes/DROME/Iml1/Iml1-deep-research-falcon.md
Iml1 encodes the Drosophila melanogaster ortholog of yeast Sea1 and human DEPDC5, forming the catalytic/scaffold subunit of the GATOR1 complex with Nprl2 and Nprl3.
|
|
GO:0005096
GTPase activator activity
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: GATOR1 has Rag GTPase GAP activity; Iml1 is a GATOR1 subunit.
Reason: GTPase-activating activity is established for GATOR1 (RagA/B), so the IEA/ISS is reasonable for Iml1 but not the primary focus.
Supporting Evidence:
PMID:23723238
GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB
|
|
GO:0051301
cell division
|
IEA
GO_REF:0000043 |
MARK AS OVER ANNOTATED |
Summary: General cell division is too broad relative to the specific mitotic-to-meiotic transition role.
Reason: Evidence indicates a specific mitotic/meiotic transition control rather than broad cell division.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition
|
|
GO:0051321
meiotic cell cycle
|
IEA
GO_REF:0000043 |
MODIFY |
Summary: Meiotic cell cycle is captured more precisely by germline mitotic-to-meiotic switching.
Reason: Use the more specific germline cell cycle switching term supported by ovarian cyst data.
Proposed replacements:
germline cell cycle switching, mitotic to meiotic cell cycle
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition
|
|
GO:0034198
cellular response to amino acid starvation
|
NAS
PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... |
ACCEPT |
Summary: Iml1 participates in the response to amino-acid starvation via GATOR1.
Reason: GATOR1 inhibition of TORC1 is central to the amino-acid starvation response.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
|
|
GO:1904262
negative regulation of TORC1 signaling
|
NAS
PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... |
ACCEPT |
Summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
Reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing branch of TORC1.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
|
|
GO:0005764
lysosome
|
IDA
PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... |
KEEP AS NON CORE |
Summary: Iml1 localizes to lysosomes as part of the GATOR complex.
Reason: GATOR complex functions at the lysosome in nutrient sensing; Iml1 is a GATOR1 subunit.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3
PMID:27166823
The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function.
|
|
GO:0051729
germline cell cycle switching, mitotic to meiotic cell cycle
|
IMP
PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entr... |
KEEP AS NON CORE |
Summary: Iml1 promotes the mitotic-to-meiotic transition in germline cysts via TORC1 inhibition.
Reason: GATOR1 members down-regulate TORC1 to promote the mitotic/meiotic transition.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition
PMID:25512509
TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila.
|
|
GO:0051729
germline cell cycle switching, mitotic to meiotic cell cycle
|
IGI
PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entr... |
KEEP AS NON CORE |
Summary: Iml1 promotes the mitotic-to-meiotic transition in germline cysts via TORC1 inhibition.
Reason: GATOR1 members down-regulate TORC1 to promote the mitotic/meiotic transition.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition
PMID:25512509
TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila.
|
|
GO:1904262
negative regulation of TORC1 signaling
|
IMP
PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entr... |
ACCEPT |
Summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
Reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing branch of TORC1.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:25512509
TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila.
|
|
GO:1904262
negative regulation of TORC1 signaling
|
IMP
PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the R... |
ACCEPT |
Summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
Reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing branch of TORC1.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:27672113
The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster.
|
|
GO:0035859
Seh1-associated complex
|
IDA
PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... |
MODIFY |
Summary: The SEA/GATOR complex term is broader than the specific GATOR1 complex membership.
Reason: Evidence supports GATOR1 subcomplex membership; use the specific GATOR1 complex term.
Proposed replacements:
GATOR1 complex
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
Component of the GATOR complex consisting of mio, Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13
PMID:27166823
The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function.
|
|
GO:1990130
GATOR1 complex
|
TAS
PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... |
ACCEPT |
Summary: Iml1 is a core subunit of the GATOR1 complex.
Reason: UniProt annotates Iml1 as a probable GATOR1 subcomplex component.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3
PMID:27166823
The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function.
|
|
GO:0032007
negative regulation of TOR signaling
|
IMP
PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTP... |
MODIFY |
Summary: This term is too general for the specific TORC1 inhibition shown for Iml1.
Reason: Evidence supports inhibition of TORC1 specifically; replace with the TORC1-specific term.
Proposed replacements:
negative regulation of TORC1 signaling
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:23723238
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
|
|
GO:0034198
cellular response to amino acid starvation
|
IMP
PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTP... |
ACCEPT |
Summary: Iml1 participates in the response to amino-acid starvation via GATOR1.
Reason: GATOR1 inhibition of TORC1 is central to the amino-acid starvation response.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:23723238
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
|
|
GO:0045792
negative regulation of cell size
|
IMP
PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTP... |
KEEP AS NON CORE |
Summary: Iml1 restrains TORC1-dependent cell growth, consistent with negative regulation of cell size.
Reason: GATOR1 inhibition of TORC1-dependent growth supports reduced cell size/growth phenotypes.
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
inhibiting TORC1-dependent cell growth
PMID:23723238
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
|
|
GO:0048142
germarium-derived cystoblast division
|
IMP
PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entr... |
KEEP AS NON CORE |
Summary: Iml1/GATOR1 regulates the mitotic divisions of germline cysts prior to meiotic entry.
Reason: Loss of GATOR1 causes ovarian cysts to undergo extra mitotic divisions before meiosis.
Supporting Evidence:
PMID:25512509
ovarian cysts undergo an extra mitotic division before meiotic entry
|
|
GO:0005096
GTPase activator activity
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: GATOR1 has Rag GTPase GAP activity; Iml1 is a GATOR1 subunit.
Reason: GTPase-activating activity is established for GATOR1 (RagA/B), so the IEA/ISS is reasonable for Iml1 but not the primary focus.
Supporting Evidence:
PMID:23723238
GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB
|
|
GO:0035859
Seh1-associated complex
|
ISS
PMID:21454883 A conserved coatomer-related complex containing Sec13 and Se... |
MODIFY |
Summary: The SEA/GATOR complex term is broader than the specific GATOR1 complex membership.
Reason: Evidence supports GATOR1 subcomplex membership; use the specific GATOR1 complex term.
Proposed replacements:
GATOR1 complex
Supporting Evidence:
file:genes/DROME/Iml1/Iml1-uniprot.txt
Component of the GATOR complex consisting of mio, Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13
PMID:21454883
A conserved coatomer-related complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces cerevisiae.
|
|
GO:0005096
GTPase activator activity
|
TAS
PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTP... |
NEW |
Summary: GATOR1 provides RagA/B GAP activity that inhibits TORC1 signaling.
Reason: GATOR1 is the Nprl2/Nprl3/Iml1 complex and is reported to have GTPase-activating protein activity for RagA/B, supporting a GTPase activator activity annotation for its subunits.
Supporting Evidence:
PMID:23723238
GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB, and its components are mutated in human cancer
|
provider: falcon
model: Edison Scientific Literature
cached: true
start_time: '2026-02-01T16:13:14.537313'
end_time: '2026-02-01T16:13:14.539520'
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template_file: templates/gene_research_go_focused.md
template_variables:
organism: DROME
gene_id: Iml1
gene_symbol: Iml1
uniprot_accession: Q9W0E3
protein_description: 'RecName: Full=GATOR complex protein Iml1 {ECO:0000303|PubMed:25512509};
AltName: Full=Increased minichromosome loss 1 {ECO:0000303|PubMed:25512509};'
gene_info: Name=Iml1 {ECO:0000303|PubMed:25512509, ECO:0000312|FlyBase:FBgn0035227};
Synonyms=DEPDC5 {ECO:0000303|PubMed:23723238}, SEA1 {ECO:0000312|FlyBase:FBgn0035227};
ORFNames=CG12090 {ECO:0000312|FlyBase:FBgn0035227};
organism_full: Drosophila melanogaster (Fruit fly).
protein_family: Belongs to the IML1 family. .
protein_domains: DEPDC5_CTD. (IPR045838); IML1. (IPR027244); IML1_double_psi_beta_barrel.
(IPR055213); IML1_N. (IPR048255); DEPDC5_CTD (PF19418)
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BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Iml1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene Iml1 (gene ID: Iml1, UniProt: Q9W0E3) in DROME.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Iml1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene Iml1 (gene ID: Iml1, UniProt: Q9W0E3) in DROME.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Plan status
- Objective 1 (verify identity): Completed. Evidence in a 2024 Drosophila-focused review maps Drosophila Iml1 to yeast Sea1 and human DEPDC5 and places it as a GATOR1 subunit alongside Nprl2 and Nprl3 (Iml1/Sea1/DEPDC5), consistent with the UniProt target context (Q9W0E3). The organism is Drosophila melanogaster. Domain annotations (IML1 family; DEPDC5_CTD) are consistent with UniProt but not detailed in the retrieved 2024 review; thus, domain verification is based on the UniProt record provided by the user and cross-species naming in the review (Sea1/Iml1/DEPDC5) (bettedi2024unveilinggator2function pages 2-4, bettedi2024unveilinggator2function pages 1-2).
- Objective 2 (search literature): Completed for 2023โ2024 developments via the 2024 review synthesizing recent fly studies on GATOR regulation, lysosome/autophagy functions, and species-specific nutrient sensing (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
- Objective 3 (gather evidence): Completed. Extracted mechanistic claims, localization, and recent developments from the 2024 review (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4, bettedi2024unveilinggator2function pages 9-10).
- Objective 4 (citation chaining): Partially completed via the 2024 reviewโs synthesis; specific 2023โ2024 primary papers are referenced within that review, but direct retrieval was insufficient; therefore, citations below primarily reference the review as a secondary, integrative source (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6).
- Objective 5 (artifact): Completed. A concise table summarizing key aspects is embedded below.
- Objective 6 (write and submit): Completed in this response.
Comprehensive research report: Drosophila Iml1 (UniProt Q9W0E3)
Executive summary
Iml1 encodes the Drosophila melanogaster ortholog of yeast Sea1 and human DEPDC5, forming the catalytic/scaffold subunit of the GATOR1 complex with Nprl2 and Nprl3. GATOR1 acts as a GAP toward RagA/B to suppress TORC1 signaling at the lysosomal surface in response to amino acid limitation. Recent Drosophila studies, synthesized in a 2024 review, refine how the opposing GATOR2 complex regulates GATOR1 and reveal TORC1-independent roles for GATOR2 in lysosome-autophagy control, as well as the emergence of a species-restricted methionine/SAM sensor that signals through GATOR2. These findings contextualize Iml1โs function in a conserved nutrient-sensing hub that governs development and metabolism in flies (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
1) Key concepts and definitions
- Identity and aliases: Iml1 is the Drosophila GATOR1 subunit orthologous to yeast Sea1 and human DEPDC5. Cross-species component tables in an authoritative 2024 review align Sea1 (yeast), Iml1 (fly), and DEPDC5 (human), supporting the alias relationships and confirming the D. melanogaster context (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 2-4).
- Complex membership and function: GATOR is divided into GATOR1 (Iml1/DEPDC5 with Nprl2/Nprl3) and GATOR2. GATOR1 serves as a negative regulator of TORC1 by acting as a GTPase-activating protein for RagA/B, thereby blocking Rag-dependent TORC1 recruitment to lysosomes under amino acid limitation (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 2-4).
- Cellular localization context: Rag GTPases localize to lysosomes and recruit TORC1 to the lysosomal surface where Rheb activates it; GATOR complexes (including GATOR2 and by context GATOR1) are found on lysosomes and autolysosomes, positioning Iml1 at this signaling hub (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
- Domain/family context: Iml1 belongs to the IML1 family and corresponds to DEPDC5 orthology; specific domain names (e.g., IML1, DEPDC5_CTD) come from the UniProt Q9W0E3 record provided in the prompt. The 2024 review supports the orthology and complex mapping (Sea1/Iml1/DEPDC5), consistent with those domain/family assignments (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 2-4).
2) Recent developments and latest research (emphasizing 2023โ2024)
- Refined GATOR2 regulation and its impact on GATOR1/TORC1: Whole-animal Drosophila studies summarized in 2023โ2024 identify WDR59 as an upstream inhibitor of GATOR2; loss of WDR59 increases GATOR1โGATOR2 interaction while decreasing GATOR1โRag interaction, altering TORC1 output and phenocopying GATOR1 mutants in specific tissues. These findings reshape how the field views GATOR2โs control of GATOR1 in vivo (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
- TORC1-independent GATOR2 role in lysosome/autophagy: Drosophila genetic analyses reveal that GATOR2 components (Wdr24, Mio, Seh1) support lysosomal acidification and autophagic flux independently of TORC1, consistent with mammalian studies that link GATOR2 to stabilization of MiT/TFE transcription factors. This reframes GATOR2 as a dual-function module and helps interpret phenotypes where TORC1 status alone does not explain defects (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 4-6).
- Species-restricted nutrient sensor for methionine/SAM: A newly characterized Drosophila methionine sensor that binds GATOR2 and is antagonized by S-adenosylmethionine (SAM) illustrates how the TORC1 pathway assimilates species-specific nutrient inputs via the GATOR hub. This discovery underscores evolutionary plasticity around a conserved core in which Iml1/GATOR1 acts as the Rag GAP arm (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 9-10).
3) Current applications and real-world implementations
- Drosophila as a system to dissect GATOR-based nutrient sensing in whole animals: The 2024 synthesis emphasizes that fly genetics and tissue-specific studies can reveal context-dependent GATOR2โGATOR1 regulation and lysosome-centric roles that are challenging to resolve in proliferative cell lines, guiding experimental design for nutrient signaling and reproductive biology. This provides a translational framework to study conserved mTORC1 control logic with organismal physiology readouts (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
4) Expert opinions and analysis from authoritative sources
- Synthesis from a Drosophila-focused review: The authors conclude that the modularity of the GATOR hub allows integration of species-specific nutrient sensors while preserving core regulation by GATOR1/Iml1 as a Rag GAP. They argue that in vivo fly work has been essential to separate TORC1-dependent versus TORC1-independent roles of GATOR2, and to illuminate tissue-specific regulation that informs how Iml1/GATOR1 function is deployed during development and stress (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
5) Relevant statistics and data from recent studies
- Genetic and phenotypic directionality: The review reports that GATOR1 component loss leads to elevated TORC1 signaling and defective response to amino acid starvation, while GATOR2 loss typically reduces TORC1 but also disrupts lysosome/autophagy in ways not rescued by TORC1 restoration. Although detailed quantitative effect sizes are study-specific, the directionality and tissue dependencies are consistently summarized across fly studies in 2023โ2024 (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
Functional annotation for Iml1 (Drosophila melanogaster; UniProt Q9W0E3)
- Primary function: Iml1 is the DEPDC5/Sea1 orthologic subunit of GATOR1, which acts as a GAP toward RagA/B to inhibit TORC1 under amino acid limitation. This positions Iml1 as a negative regulator of nutrient-induced TORC1 activation via the Rag GTPase axis (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 2-4).
- Substrates/partners: The immediate biochemical โsubstrateโ of GATOR1 is RagA/B (Rag GTPases); in flies, GATOR1 antagonizes Rag-mediated TORC1 recruitment/activation at lysosomes. Iml1 functions with Nprl2 and Nprl3 in this trimeric complex (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 2-4).
- Localization/site of action: The GATOR hub and RagโTORC1 interaction occur on lysosomal/autolysosomal membranesโthe site of TORC1 activation by Rhebโplacing Iml1 where Rag recruitment and GAP regulation are spatially integrated (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
- Pathway context: Iml1/GATOR1 integrates amino acid availability upstream of TORC1 via Rag GTPases. GATOR2 acts upstream/parallel to modulate GATOR1 and also exerts TORC1-independent control of lysosome-autophagy programs, shaping the net metabolic output in a tissue- and context-specific manner (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
Verification of identity and addressing symbol ambiguity
- The symbol Iml1 in Drosophila melanogaster matches the GATOR1 subunit orthologous to yeast Sea1 and human DEPDC5. The organism is D. melanogaster, and the complex mapping Sea1โIml1โDEPDC5 is explicitly presented in the 2024 review. Domain/family annotations (IML1 family; DEPDC5_CTD) are provided in the UniProt record Q9W0E3 supplied by the user and are consistent with cross-species component naming in the review (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 2-4).
Practical implications and open questions
- The fly literature indicates that interpreting Iml1/GATOR1 phenotypes often requires considering GATOR2โs TORC1-independent lysosomal role and emerging species-specific nutrient sensors. This raises testable hypotheses about how Iml1-linked regulation of Rag/TORC1 is modulated by tissue-specific GATOR2 states, and how lysosome-autophagy programs crosstalk to impact development (Bettedi et al., Cells, 30 Oct 2024; https://doi.org/10.3390/cells13211795) (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6).
Embedded quick-reference summary
| Aspect | Summary (Drosophila-focused) | Key details | Source / Date / URL |
|---|---|---|---|
| Identity | Iml1 โ Drosophila GATOR1 subunit | Ortholog of yeast Sea1 and human DEPDC5; identified as a core GATOR1-related protein in flies. | Bettedi et al., Cells; Published 30 Oct 2024; https://doi.org/10.3390/cells13211795 (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 2-4) |
| Aliases | Sea1; DEPDC5 (human ortholog) | Iml1 is listed alongside Sea1/DEPDC5 in cross-species mappings of GATOR/SEA components. | Bettedi et al., Cells; Published 30 Oct 2024; https://doi.org/10.3390/cells13211795 (bettedi2024unveilinggator2function pages 2-4) |
| Complex membership | Member of trimeric GATOR1 (with Nprl2 and Nprl3) | GATOR1 is the inhibitory subcomplex that functionally opposes GATOR2; Iml1 acts with Nprl2/Nprl3. | Bettedi et al., Cells; Published 30 Oct 2024; https://doi.org/10.3390/cells13211795 (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 4-6) |
| Pathway role | Negative regulator of TORC1 via Rag GTPases | GATOR1 (DEPDC5/Iml1 + NPRL2 + NPRL3) functions as a GAP toward RagA/B to prevent Rag-mediated recruitment of TORC1 to lysosomes and thereby inhibit TORC1 activation in response to amino-acid limitation. | Bettedi et al., Cells; Published 30 Oct 2024; https://doi.org/10.3390/cells13211795 (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 2-4) |
| Cellular localization | Lysosome / autolysosome surfaces (flies and mammals) | GATOR complexes localize to lysosomal/autolysosomal membranes where Rag GTPases recruit TORC1; localization underlies regulation of TORC1 and lysosome/autophagy processes. | Bettedi et al., Cells; Published 30 Oct 2024; https://doi.org/10.3390/cells13211795 (bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4) |
| 2023โ2024 Drosophila developments | Whole-animal fly studies refined GATOR regulation and revealed new lysosomal roles | Recent fly work (2023โ2024) clarified GATOR2 regulation (e.g., WDR59 can act as an upstream inhibitor of GATOR2), demonstrated TORC1-independent roles for GATOR2 in maintaining lysosomalโautophagic function, and highlighted species-specific nutrient sensors (a fly methionine sensor signaling via GATOR2). | Bettedi et al., Cells; Published 30 Oct 2024; https://doi.org/10.3390/cells13211795 (bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6) |
Table: Concise table summarizing Iml1 identity, complex membership, pathway role, localization, and 2023โ2024 Drosophila findings, with citation to Bettedi et al., Cells (30 Oct 2024) for each entry.
Cited source (URLs and dates)
- Bettedi L, Zhang Y, Yang S, Lilly MA. Unveiling GATOR2 Function: Novel Insights from Drosophila Research. Cells. Published 30 Oct 2024. DOI: 10.3390/cells13211795. URL: https://doi.org/10.3390/cells13211795 (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4, bettedi2024unveilinggator2function pages 9-10).
Notes on evidence coverage
- The mechanistic core (Iml1/DEPDC5 orthology; GATOR1 as RagA/B GAP; lysosomal localization of the RagโTORC1 hub) and the 2023โ2024 Drosophila developments (GATOR2 regulation, lysosome/autophagy roles, methionine/SAM sensor) are documented in the 2024 review cited above. Specific domain names for Iml1 (IML1 family; DEPDC5_CTD) derive from the UniProt record provided in the prompt; the review provides orthology support but does not enumerate domains explicitly (bettedi2024unveilinggator2function pages 1-2, bettedi2024unveilinggator2function pages 7-9, bettedi2024unveilinggator2function pages 4-6, bettedi2024unveilinggator2function pages 2-4).
References
(bettedi2024unveilinggator2function pages 2-4): Lucia Bettedi, Yingbiao Zhang, Shu Yang, and Mary A. Lilly. Unveiling gator2 function: novel insights from drosophila research. Cells, 13:1795, Oct 2024. URL: https://doi.org/10.3390/cells13211795, doi:10.3390/cells13211795. This article has 2 citations and is from a poor quality or predatory journal.
(bettedi2024unveilinggator2function pages 1-2): Lucia Bettedi, Yingbiao Zhang, Shu Yang, and Mary A. Lilly. Unveiling gator2 function: novel insights from drosophila research. Cells, 13:1795, Oct 2024. URL: https://doi.org/10.3390/cells13211795, doi:10.3390/cells13211795. This article has 2 citations and is from a poor quality or predatory journal.
(bettedi2024unveilinggator2function pages 7-9): Lucia Bettedi, Yingbiao Zhang, Shu Yang, and Mary A. Lilly. Unveiling gator2 function: novel insights from drosophila research. Cells, 13:1795, Oct 2024. URL: https://doi.org/10.3390/cells13211795, doi:10.3390/cells13211795. This article has 2 citations and is from a poor quality or predatory journal.
(bettedi2024unveilinggator2function pages 4-6): Lucia Bettedi, Yingbiao Zhang, Shu Yang, and Mary A. Lilly. Unveiling gator2 function: novel insights from drosophila research. Cells, 13:1795, Oct 2024. URL: https://doi.org/10.3390/cells13211795, doi:10.3390/cells13211795. This article has 2 citations and is from a poor quality or predatory journal.
(bettedi2024unveilinggator2function pages 9-10): Lucia Bettedi, Yingbiao Zhang, Shu Yang, and Mary A. Lilly. Unveiling gator2 function: novel insights from drosophila research. Cells, 13:1795, Oct 2024. URL: https://doi.org/10.3390/cells13211795, doi:10.3390/cells13211795. This article has 2 citations and is from a poor quality or predatory journal.
id: Q9W0E3
gene_symbol: Iml1
product_type: PROTEIN
status: INITIALIZED
taxon:
id: NCBITaxon:7227
label: Drosophila melanogaster
description: 'DEPDC5/Iml1 GATOR1 subunit that suppresses TORC1 to control meiotic
entry and oocyte development.'
alternative_products:
- name: A {ECO:0000312|FlyBase:FBgn0035227}
id: Q9W0E3-1
- name: B {ECO:0000312|FlyBase:FBgn0035227}
id: Q9W0E3-2
sequence_note: VSP_060140, VSP_060141
existing_annotations:
- term:
id: GO:0010508
label: positive regulation of autophagy
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Iml1 supports autophagy during nutrient stress via TORC1
inhibition.
action: KEEP_AS_NON_CORE
reason: UniProt notes GATOR1 promotes survival under starvation by promoting
autophagy.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: promoting survival during amino acid or complete
starvation by inhibiting TORC1-dependent cell growth and promoting
catabolic metabolism and autophagy
- term:
id: GO:0034198
label: cellular response to amino acid starvation
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Iml1 participates in the response to amino-acid starvation via
GATOR1.
action: ACCEPT
reason: GATOR1 inhibition of TORC1 is central to the amino-acid starvation
response.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- term:
id: GO:1904262
label: negative regulation of TORC1 signaling
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
action: ACCEPT
reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing
branch of TORC1.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- term:
id: GO:0005765
label: lysosomal membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Lysosomal membrane association is consistent with GATOR
localization at lysosomes.
action: KEEP_AS_NON_CORE
reason: GATOR complex functions at the lysosome in nutrient sensing; Iml1 is
a GATOR1 subunit.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: probable component of the GATOR1 subcomplex which is
likely composed of Iml1, Nplr2 and Nplr3
- term:
id: GO:1990130
label: GATOR1 complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Iml1 is a core subunit of the GATOR1 complex.
action: ACCEPT
reason: UniProt annotates Iml1 as a probable GATOR1 subcomplex component.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: probable component of the GATOR1 subcomplex which is
likely composed of Iml1, Nplr2 and Nplr3
- reference_id: file:genes/DROME/Iml1/Iml1-deep-research-falcon.md
supporting_text: Iml1 encodes the Drosophila melanogaster ortholog of
yeast Sea1 and human DEPDC5, forming the catalytic/scaffold subunit of
the GATOR1 complex with Nprl2 and Nprl3.
- term:
id: GO:0005096
label: GTPase activator activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
review: &id002
summary: GATOR1 has Rag GTPase GAP activity; Iml1 is a GATOR1 subunit.
action: KEEP_AS_NON_CORE
reason: GTPase-activating activity is established for GATOR1 (RagA/B), so
the IEA/ISS is reasonable for Iml1 but not the primary focus.
supported_by:
- reference_id: PMID:23723238
supporting_text: GATOR1 has GTPase-activating protein (GAP) activity for
RagA and RagB
- term:
id: GO:0051301
label: cell division
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: General cell division is too broad relative to the specific
mitotic-to-meiotic transition role.
action: MARK_AS_OVER_ANNOTATED
reason: Evidence indicates a specific mitotic/meiotic transition control
rather than broad cell division.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: down-regulate TORC1 to slow cellular metabolism and
promote the mitotic/meiotic transition
- term:
id: GO:0051321
label: meiotic cell cycle
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: Meiotic cell cycle is captured more precisely by germline
mitotic-to-meiotic switching.
action: MODIFY
reason: Use the more specific germline cell cycle switching term supported
by ovarian cyst data.
proposed_replacement_terms:
- id: GO:0051729
label: germline cell cycle switching, mitotic to meiotic cell cycle
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: down-regulate TORC1 to slow cellular metabolism and
promote the mitotic/meiotic transition
- term:
id: GO:0034198
label: cellular response to amino acid starvation
evidence_type: NAS
original_reference_id: PMID:24786828
review:
summary: Iml1 participates in the response to amino-acid starvation via
GATOR1.
action: ACCEPT
reason: GATOR1 inhibition of TORC1 is central to the amino-acid starvation
response.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- reference_id: PMID:24786828
supporting_text: The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive
response to amino-acid starvation in Drosophila.
- term:
id: GO:1904262
label: negative regulation of TORC1 signaling
evidence_type: NAS
original_reference_id: PMID:24786828
review:
summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
action: ACCEPT
reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing
branch of TORC1.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- reference_id: PMID:24786828
supporting_text: The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive
response to amino-acid starvation in Drosophila.
- term:
id: GO:0005764
label: lysosome
evidence_type: IDA
original_reference_id: PMID:27166823
review:
summary: Iml1 localizes to lysosomes as part of the GATOR complex.
action: KEEP_AS_NON_CORE
reason: GATOR complex functions at the lysosome in nutrient sensing; Iml1 is
a GATOR1 subunit.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: probable component of the GATOR1 subcomplex which is
likely composed of Iml1, Nplr2 and Nplr3
- reference_id: PMID:27166823
supporting_text: The GATOR2 Component Wdr24 Regulates TORC1 Activity and
Lysosome Function.
- term:
id: GO:0051729
label: germline cell cycle switching, mitotic to meiotic cell cycle
evidence_type: IMP
original_reference_id: PMID:25512509
review: &id001
summary: Iml1 promotes the mitotic-to-meiotic transition in germline cysts
via TORC1 inhibition.
action: KEEP_AS_NON_CORE
reason: GATOR1 members down-regulate TORC1 to promote the mitotic/meiotic
transition.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: down-regulate TORC1 to slow cellular metabolism and
promote the mitotic/meiotic transition
- reference_id: PMID:25512509
supporting_text: TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic
entry and oocyte development in Drosophila.
- term:
id: GO:0051729
label: germline cell cycle switching, mitotic to meiotic cell cycle
evidence_type: IGI
original_reference_id: PMID:25512509
review: *id001
- term:
id: GO:1904262
label: negative regulation of TORC1 signaling
evidence_type: IMP
original_reference_id: PMID:25512509
review:
summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
action: ACCEPT
reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing
branch of TORC1.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- reference_id: PMID:25512509
supporting_text: TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic
entry and oocyte development in Drosophila.
- term:
id: GO:1904262
label: negative regulation of TORC1 signaling
evidence_type: IMP
original_reference_id: PMID:27672113
review:
summary: Iml1 inhibits TORC1 signaling as part of GATOR1.
action: ACCEPT
reason: UniProt describes GATOR1 as an inhibitor of the amino acid-sensing
branch of TORC1.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- reference_id: PMID:27672113
supporting_text: The GATOR1 Complex Regulates Metabolic Homeostasis and
the Response to Nutrient Stress in Drosophila melanogaster.
- term:
id: GO:0035859
label: Seh1-associated complex
evidence_type: IDA
original_reference_id: PMID:27166823
review:
summary: The SEA/GATOR complex term is broader than the specific GATOR1
complex membership.
action: MODIFY
reason: Evidence supports GATOR1 subcomplex membership; use the specific
GATOR1 complex term.
proposed_replacement_terms:
- id: GO:1990130
label: GATOR1 complex
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: Component of the GATOR complex consisting of mio,
Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13
- reference_id: PMID:27166823
supporting_text: The GATOR2 Component Wdr24 Regulates TORC1 Activity and
Lysosome Function.
- term:
id: GO:1990130
label: GATOR1 complex
evidence_type: TAS
original_reference_id: PMID:27166823
review:
summary: Iml1 is a core subunit of the GATOR1 complex.
action: ACCEPT
reason: UniProt annotates Iml1 as a probable GATOR1 subcomplex component.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: probable component of the GATOR1 subcomplex which is
likely composed of Iml1, Nplr2 and Nplr3
- reference_id: PMID:27166823
supporting_text: The GATOR2 Component Wdr24 Regulates TORC1 Activity and
Lysosome Function.
- term:
id: GO:0032007
label: negative regulation of TOR signaling
evidence_type: IMP
original_reference_id: PMID:23723238
review:
summary: This term is too general for the specific TORC1 inhibition shown
for Iml1.
action: MODIFY
reason: Evidence supports inhibition of TORC1 specifically; replace with the
TORC1-specific term.
proposed_replacement_terms:
- id: GO:1904262
label: negative regulation of TORC1 signaling
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- reference_id: PMID:23723238
supporting_text: A Tumor suppressor complex with GAP activity for the Rag
GTPases that signal amino acid sufficiency to mTORC1.
- term:
id: GO:0034198
label: cellular response to amino acid starvation
evidence_type: IMP
original_reference_id: PMID:23723238
review:
summary: Iml1 participates in the response to amino-acid starvation via
GATOR1.
action: ACCEPT
reason: GATOR1 inhibition of TORC1 is central to the amino-acid starvation
response.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: functions as an inhibitor of the amino acid-sensing
branch of the TORC1 signaling pathway
- reference_id: PMID:23723238
supporting_text: A Tumor suppressor complex with GAP activity for the Rag
GTPases that signal amino acid sufficiency to mTORC1.
- term:
id: GO:0045792
label: negative regulation of cell size
evidence_type: IMP
original_reference_id: PMID:23723238
review:
summary: Iml1 restrains TORC1-dependent cell growth, consistent with
negative regulation of cell size.
action: KEEP_AS_NON_CORE
reason: GATOR1 inhibition of TORC1-dependent growth supports reduced cell
size/growth phenotypes.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: inhibiting TORC1-dependent cell growth
- reference_id: PMID:23723238
supporting_text: A Tumor suppressor complex with GAP activity for the Rag
GTPases that signal amino acid sufficiency to mTORC1.
- term:
id: GO:0048142
label: germarium-derived cystoblast division
evidence_type: IMP
original_reference_id: PMID:25512509
review:
summary: Iml1/GATOR1 regulates the mitotic divisions of germline cysts prior
to meiotic entry.
action: KEEP_AS_NON_CORE
reason: Loss of GATOR1 causes ovarian cysts to undergo extra mitotic
divisions before meiosis.
supported_by:
- reference_id: PMID:25512509
supporting_text: ovarian cysts undergo an extra mitotic division before
meiotic entry
- term:
id: GO:0005096
label: GTPase activator activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
review: *id002
- term:
id: GO:0035859
label: Seh1-associated complex
evidence_type: ISS
original_reference_id: PMID:21454883
review:
summary: The SEA/GATOR complex term is broader than the specific GATOR1
complex membership.
action: MODIFY
reason: Evidence supports GATOR1 subcomplex membership; use the specific
GATOR1 complex term.
proposed_replacement_terms:
- id: GO:1990130
label: GATOR1 complex
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-uniprot.txt
supporting_text: Component of the GATOR complex consisting of mio,
Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13
- reference_id: PMID:21454883
supporting_text: A conserved coatomer-related complex containing Sec13 and
Seh1 dynamically associates with the vacuole in Saccharomyces
cerevisiae.
- term:
id: GO:0005096
label: GTPase activator activity
evidence_type: TAS
original_reference_id: PMID:23723238
review:
summary: GATOR1 provides RagA/B GAP activity that inhibits TORC1 signaling.
action: NEW
reason: GATOR1 is the Nprl2/Nprl3/Iml1 complex and is reported to have
GTPase-activating protein activity for RagA/B, supporting a GTPase
activator activity annotation for its subunits.
supported_by:
- reference_id: PMID:23723238
supporting_text: GATOR1 has GTPase-activating protein (GAP) activity for
RagA and RagB, and its components are mutated in human cancer
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with
GO terms
findings: []
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to
orthologs by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings: []
- id: PMID:21454883
title: A conserved coatomer-related complex containing Sec13 and Seh1
dynamically associates with the vacuole in Saccharomyces cerevisiae.
findings: []
- id: PMID:23723238
title: A Tumor suppressor complex with GAP activity for the Rag GTPases that
signal amino acid sufficiency to mTORC1.
findings: []
- id: PMID:24786828
title: The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to
amino-acid starvation in Drosophila.
findings: []
- id: PMID:25512509
title: TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and
oocyte development in Drosophila.
findings: []
- id: PMID:27166823
title: The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome
Function.
findings: []
- id: PMID:27672113
title: The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to
Nutrient Stress in Drosophila melanogaster.
findings: []
core_functions:
- description: Iml1 (DEPDC5) is a GATOR1 subunit that scaffolds Rag
GTPase-activating activity to inhibit TORC1 signaling.
supported_by:
- reference_id: file:genes/DROME/Iml1/Iml1-deep-research-falcon.md
supporting_text: Iml1 encodes the Drosophila melanogaster ortholog of yeast
Sea1 and human DEPDC5, forming the catalytic/scaffold subunit of the
GATOR1 complex with Nprl2 and Nprl3.
- reference_id: PMID:25512509
supporting_text: the Iml1/GATOR1 complex inhibits TORC1 activity to slow
cellular metabolism and drive the mitotic/meiotic transition in developing
ovarian cysts.
molecular_function:
id: GO:0005096
label: GTPase activator activity
directly_involved_in:
- id: GO:1904262
label: negative regulation of TORC1 signaling
- id: GO:0034198
label: cellular response to amino acid starvation
in_complex:
id: GO:1990130
label: GATOR1 complex