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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FlyBase

(Nprl2-deep-research-flybase.md)
FlyBase gene description for Nprl2 (DROME) FlyBase

FlyBase gene description for Nprl2 (DROME)

Nitrogen permease regulator-like 2 (Nprl2) encodes a component of the highly conserved GAP activity towards rags 1 (GATOR1) complex, which inhibits the product of mTor activity in response to amino acid starvation. The product of Nprl2, as well as the other GATOR1 components encoded by Nprl3 and Iml1, regulates early meiotic progression.

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