Nprl2

UniProt ID: Q9VXA0
Organism: Drosophila melanogaster
Review Status: INITIALIZED
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Gene Description

GATOR1 complex subunit that inhibits TORC1 signaling during amino acid limitation and nutrient stress.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0034198 cellular response to amino acid starvation
IBA
GO_REF:0000033
ACCEPT
Summary: Nprl2 participates in the response to amino-acid starvation.
Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation.
Supporting Evidence:
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
GO:0005096 GTPase activator activity
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: GATOR1 has Rag GTPase GAP activity; Nprl2 is a GATOR1 subunit.
Reason: GTPase-activating activity is established for GATOR1 (RagA/B), so the IBA is reasonable for Nprl2 but not the primary focus.
Supporting Evidence:
PMID:23723238
GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB
GO:1904262 negative regulation of TORC1 signaling
IBA
GO_REF:0000033
ACCEPT
Summary: Nprl2 inhibits TORC1 signaling, especially under amino-acid starvation.
Reason: Both UniProt and the starvation study describe Nprl2-mediated inhibition of TORC1 in response to amino-acid limitation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.
GO:0005774 vacuolar membrane
IBA
GO_REF:0000033
MODIFY
Summary: The vacuolar membrane term is yeast-specific; Drosophila data indicate lysosomal localization.
Reason: Replace vacuolar membrane with lysosome to match the Drosophila localization evidence.
Proposed replacements: lysosome
Supporting Evidence:
PMID:24786828
Nprl2 and Nprl3 physically interact and are targeted to lysosomes and autolysosomes
GO:1990130 GATOR1 complex
IBA
GO_REF:0000033
ACCEPT
Summary: Nprl2 is a core subunit of the GATOR1 complex.
Reason: UniProt annotates Nprl2 as a probable GATOR1 subcomplex component, supporting this complex membership.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3
file:genes/DROME/Nprl2/Nprl2-deep-research-falcon.md
Nprl2 is one of three core subunits of GATOR1 (with Iml1/DEPDC5 and Nprl3).
GO:0005737 cytoplasm
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Nprl2 localizes to the cytoplasm.
Reason: UniProt reports cytoplasmic localization.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005764 lysosome
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Nprl2 localizes to lysosomes under nutrient stress.
Reason: Lysosomal targeting is reported for Nprl2/Nprl3.
Supporting Evidence:
PMID:24786828
Nprl2 and Nprl3 physically interact and are targeted to lysosomes and autolysosomes
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/Nprl2/Nprl2-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.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition
GO:1904262 negative regulation of TORC1 signaling
IEA
GO_REF:0000117
ACCEPT
Summary: Nprl2 inhibits TORC1 signaling, especially under amino-acid starvation.
Reason: Both UniProt and the starvation study describe Nprl2-mediated inhibition of TORC1 in response to amino-acid limitation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.
GO:0034198 cellular response to amino acid starvation
NAS
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
ACCEPT
Summary: Nprl2 participates in the response to amino-acid starvation.
Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation.
Supporting Evidence:
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: Nprl2 inhibits TORC1 signaling, especially under amino-acid starvation.
Reason: Both UniProt and the starvation study describe Nprl2-mediated inhibition of TORC1 in response to amino-acid limitation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.
GO:1904262 negative regulation of TORC1 signaling
IMP
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
ACCEPT
Summary: Nprl2 inhibits TORC1 signaling, especially under amino-acid starvation.
Reason: Both UniProt and the starvation study describe Nprl2-mediated inhibition of TORC1 in response to amino-acid limitation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.
GO:0009267 cellular response to starvation
IMP
PMID:27672113
The GATOR1 Complex Regulates Metabolic Homeostasis and the R...
KEEP AS NON CORE
Summary: Starvation response is supported but primarily in the amino-acid limitation context.
Reason: Evidence supports amino-acid starvation response; the broader starvation term is acceptable but not core.
Supporting Evidence:
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
PMID:27672113
The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster.
GO:0010898 positive regulation of triglyceride catabolic process
IMP
PMID:27672113
The GATOR1 Complex Regulates Metabolic Homeostasis and the R...
MARK AS OVER ANNOTATED
Summary: Nprl2 affects TAG storage, but direct positive regulation of triglyceride catabolism is not shown.
Reason: Reported phenotype is reduced TAG storage in mutants, which does not directly demonstrate increased triglyceride catabolism.
Supporting Evidence:
PMID:27672113
nprl2 and nprl3 mutant adults contain reduced amounts of stored TAG relative to wild-type animals
GO:1904262 negative regulation of TORC1 signaling
IGI
PMID:27672113
The GATOR1 Complex Regulates Metabolic Homeostasis and the R...
ACCEPT
Summary: Nprl2 inhibits TORC1 signaling, especially under amino-acid starvation.
Reason: Both UniProt and the starvation study describe Nprl2-mediated inhibition of TORC1 in response to amino-acid limitation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.
PMID:27672113
The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster.
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: Nprl2 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/Nprl2/Nprl2-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:27672113
The GATOR1 Complex Regulates Metabolic Homeostasis and the R...
ACCEPT
Summary: Nprl2 inhibits TORC1 signaling, especially under amino-acid starvation.
Reason: Both UniProt and the starvation study describe Nprl2-mediated inhibition of TORC1 in response to amino-acid limitation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.
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/Nprl2/Nprl2-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:1904262 negative regulation of TORC1 signaling
IGI
PMID:27166823
The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso...
ACCEPT
Summary: Nprl2 inhibits TORC1 signaling, especially under amino-acid starvation.
Reason: Both UniProt and the starvation study describe Nprl2-mediated inhibition of TORC1 in response to amino-acid limitation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway
PMID:24786828
Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.
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: Nprl2 is a core subunit of the GATOR1 complex.
Reason: UniProt annotates Nprl2 as a probable GATOR1 subcomplex component, supporting this complex membership.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-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 Nprl2.
Reason: Evidence supports inhibition of TORC1 specifically; replace with the TORC1-specific term.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-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: Nprl2 participates in the response to amino-acid starvation.
Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation.
Supporting Evidence:
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
PMID:23723238
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
GO:0007293 germarium-derived egg chamber formation
IGI
PMID:25512509
TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entr...
MODIFY
Summary: Evidence points to oogenesis/meiotic entry roles rather than the specific egg chamber formation term.
Reason: Use the broader oogenesis term supported by meiotic entry/oocyte development data.
Proposed replacements: oogenesis
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
control meiotic entry and promote oocyte growth and development
PMID:25512509
TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila.
GO:0005515 protein binding
IPI
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
KEEP AS NON CORE
Summary: Nprl2 physically interacts with Nprl3.
Reason: Interaction evidence supports protein binding, but the term is generic and not core.
Supporting Evidence:
PMID:24786828
Nprl2 and Nprl3 physically interact
GO:0005634 nucleus
IDA
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
UNDECIDED
Summary: Nuclear localization is not supported by the accessible sources used for this review.
Reason: Available curated localization statements emphasize cytoplasm/lysosome/autolysosome without nuclear evidence.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm. Lysosome
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
GO:0005737 cytoplasm
IDA
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
KEEP AS NON CORE
Summary: Nprl2 localizes to the cytoplasm.
Reason: UniProt reports cytoplasmic localization.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
GO:0034198 cellular response to amino acid starvation
IMP
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
ACCEPT
Summary: Nprl2 participates in the response to amino-acid starvation.
Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation.
Supporting Evidence:
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
GO:0044754 autolysosome
IDA
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
KEEP AS NON CORE
Summary: Nprl2 localizes to autolysosomes during amino-acid starvation.
Reason: UniProt notes primary localization to autolysosomes under amino-acid starvation.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
Localizes primarily to the autolysosomes during amino-acid starvation
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
GO:0045792 negative regulation of cell size
IMP
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
KEEP AS NON CORE
Summary: Nprl2 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/Nprl2/Nprl2-uniprot.txt
inhibiting TORC1-dependent cell growth
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
GO:0048477 oogenesis
IMP
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res...
KEEP AS NON CORE
Summary: Nprl2 participates in oogenesis through GATOR1 control of meiotic entry and oocyte development.
Reason: UniProt describes GATOR1 roles in meiotic entry and oocyte growth.
Supporting Evidence:
file:genes/DROME/Nprl2/Nprl2-uniprot.txt
control meiotic entry and promote oocyte growth and development
PMID:24786828
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
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/Nprl2/Nprl2-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.

Core Functions

Nprl2 is a GATOR1 subunit that contributes to Rag GTPase-activating activity to inhibit TORC1 during amino acid starvation.

Supporting Evidence:
  • file:genes/DROME/Nprl2/Nprl2-deep-research-falcon.md
    Nprl2 is one of three core subunits of GATOR1 (with Iml1/DEPDC5 and Nprl3).
  • PMID:24786828
    Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation.

References

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Deep Research

Falcon

(Nprl2-deep-research-falcon.md)

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