Cup is a large germline-enriched eIF4E-binding protein of the 4E-T family that represses translation of localized maternal mRNAs in the Drosophila ovary and early embryo. Recruited to oskar mRNA by Bruno and to nanos mRNA by Smaug, Cup binds the cap-binding factor eIF4E1 through a canonical YXXXXL motif and a non-canonical lateral motif, displacing eIF4G and blocking 43S ribosome recruitment; an eIF4E-independent effector domain recruits the CCR4-NOT deadenylase and decapping activators, leaving targets deadenylated but protected from decay. Cup is a component of germline P bodies with Me31B and Tral, is required for oskar localization (recruiting Barentsz), gurken regulation and oogenesis, shuttles between nucleus and cytoplasm, and also acts at larval neuromuscular junctions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening | TAS PMID:36951092 RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent... | ACCEPT | Summary: Cup is a co-repressor in the Smaug-nanos RNP that recruits CCR4-NOT and promotes deadenylation of target mRNAs. Reason: Reconstitution and tethering studies show that Cup is part of the Smaug-dependent repressor complex that induces CCR4-NOT deadenylation, and that the Cup effector domain associates with CAF1-CCR4-NOT and promotes deadenylation of bound mRNAs. Cup therefore contributes mechanistically to poly(A) shortening of its targets. Supporting Evidence: PMID:36951092 The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4-NOT deadenylase PMID:21937713 CUP maintains mRNA targets in a repressed state by promoting their deadenylation and protects deadenylated mRNAs from further degradation PMID:21937713 This domain associates with the deadenylase complex CAF1-CCR4-NOT and decapping activators |
| GO:0000932 P-body | IDA PMID:16256742 Efficient protein trafficking requires trailer hitch, a comp... | ACCEPT | Summary: Cup localizes to P bodies (germline RNP granules) in nurse cells and oocytes. Reason: Multiple independent imaging studies in Drosophila egg chambers place Cup in P bodies with Me31B and Tral, consistent with its role in storing translationally repressed maternal mRNAs. Supporting Evidence: PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) PMID:23178881 Similarly, Cup and Eukaryotic initiation factor 4E (eIF4E) colocalize with P bodies |
| GO:0000932 P-body | IDA PMID:19464282 The spinal muscular atrophy protein SMN affects Drosophila g... | ACCEPT | Summary: Cup localizes to P bodies (germline RNP granules) in nurse cells and oocytes. Reason: Multiple independent imaging studies in Drosophila egg chambers place Cup in P bodies with Me31B and Tral, consistent with its role in storing translationally repressed maternal mRNAs. Supporting Evidence: PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) PMID:23178881 Similarly, Cup and Eukaryotic initiation factor 4E (eIF4E) colocalize with P bodies |
| GO:0000932 P-body | IDA PMID:20452345 Drosophila SMN complex proteins Gemin2, Gemin3, and Gemin5 a... | ACCEPT | Summary: Cup localizes to P bodies (germline RNP granules) in nurse cells and oocytes. Reason: Multiple independent imaging studies in Drosophila egg chambers place Cup in P bodies with Me31B and Tral, consistent with its role in storing translationally repressed maternal mRNAs. Supporting Evidence: PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) PMID:23178881 Similarly, Cup and Eukaryotic initiation factor 4E (eIF4E) colocalize with P bodies |
| GO:0000932 P-body | IDA PMID:21939654 U bodies respond to nutrient stress in Drosophila. | ACCEPT | Summary: Cup localizes to P bodies (germline RNP granules) in nurse cells and oocytes. Reason: Multiple independent imaging studies in Drosophila egg chambers place Cup in P bodies with Me31B and Tral, consistent with its role in storing translationally repressed maternal mRNAs. Supporting Evidence: PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) PMID:23178881 Similarly, Cup and Eukaryotic initiation factor 4E (eIF4E) colocalize with P bodies |
| GO:0000932 P-body | IDA PMID:23178881 Drosophila patterning is established by differential associa... | ACCEPT | Summary: Cup localizes to P bodies (germline RNP granules) in nurse cells and oocytes. Reason: Multiple independent imaging studies in Drosophila egg chambers place Cup in P bodies with Me31B and Tral, consistent with its role in storing translationally repressed maternal mRNAs. Supporting Evidence: PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) PMID:23178881 Similarly, Cup and Eukaryotic initiation factor 4E (eIF4E) colocalize with P bodies |
| GO:0000932 P-body | IDA NOT PMID:24335285 Human 4E-T represses translation of bound mRNAs and enhances... | REMOVE | Summary: NOT annotation stating that Cup is not located in P bodies, based on GFP-Cup expressed in human HeLa cells. Reason: The negative result was obtained by heterologous expression of Drosophila Cup in HeLa cells, where the authors themselves attribute it to the absence of fly cofactors. In its native context Cup is a well-documented P-body component in Drosophila egg chambers, so the NOT statement does not describe Cup biology and is contradicted by several FlyBase IDA annotations. Supporting Evidence: PMID:24335285 we observed that Drosophila Cup, which lacks these sequences, does not localize to P-bodies in HeLa cells PMID:24335285 could simply reflect the lack of appropriate fly cofactors in mammalian cells PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) |
| GO:0000932 P-body | IDA PMID:37553798 Cup is essential for oskar mRNA translational repression dur... | ACCEPT | Summary: Cup localizes to P bodies (germline RNP granules) in nurse cells and oocytes. Reason: Multiple independent imaging studies in Drosophila egg chambers place Cup in P bodies with Me31B and Tral, consistent with its role in storing translationally repressed maternal mRNAs. Supporting Evidence: PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) PMID:23178881 Similarly, Cup and Eukaryotic initiation factor 4E (eIF4E) colocalize with P bodies |
| GO:0003723 RNA binding | IDA PMID:16469699 Bruno acts as a dual repressor of oskar translation, promoti... | UNDECIDED | Summary: RNA binding by Cup, attributed to the Bruno/oskar silencing study. Reason: Cup has no recognized RNA-binding domain and is recruited to oskar and nanos mRNAs by the RNA-binding proteins Bruno and Smaug. The cached abstract describes Cup as an eIF4E-binding protein that interacts with Bruno; it does not show direct RNA binding by Cup, and the full text was not available to check the assay behind this IDA. Supporting Evidence: PMID:16469699 The eIF4E binding protein Cup interacts with Bruno and inhibits oskar translation |
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: mRNA binding propagated by IBA across the 4E-T/Cup family. Reason: Cup associates with target mRNAs within RNPs, but recruitment is through sequence-specific RNA-binding partners (Bruno, Smaug) and via eIF4E at the cap. Direct, sequence-independent mRNA binding by Cup has not been demonstrated, so the propagated mRNA binding term overstates its molecular activity relative to its eIF4E-binding and repressor functions. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN001283523 SUPPORTS SOURCE BUT NOT TARGET Family members associate with mRNPs, but Drosophila Cup is recruited to its targets indirectly through Bruno, Smaug and eIF4E; mRNP association is conflated with direct mRNA binding. Supporting Evidence: PMID:14685270 Cup mediates an indirect interaction between Smaug and eIF4E PMID:14691132 Thus, Cup is a translational repressor of oskar that is required to assemble the oskar mRNA localization machinery |
| GO:0005515 protein binding | IPI PMID:14605208 A protein interaction map of Drosophila melanogaster. | REMOVE | Summary: Generic protein binding (Cup with Me31B). Reason: Protein binding is uninformative. The Cup-Me31B association reflects co-membership of repressive maternal RNPs, which is captured by the P-body and translational repression annotations. Removal does not dispute the interaction. Supporting Evidence: PMID:21937713 This domain associates with the deadenylase complex CAF1-CCR4-NOT and decapping activators |
| GO:0005515 protein binding | IPI PMID:14685270 Drosophila Cup is an eIF4E-binding protein that functions in... | MODIFY | Summary: Protein binding between Cup and eIF4E1. Reason: Cup binds eIF4E through a canonical YXXXXL motif plus a non-canonical lateral motif; the informative term is eukaryotic initiation factor 4E binding. Proposed replacements: eukaryotic initiation factor 4E binding Supporting Evidence: PMID:14685270 Cup is an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E PMID:14723848 Cup binds the 5'-cap binding translation initiation factor eIF4E through a sequence conserved among eIF4E binding proteins |
| GO:0005515 protein binding | IPI PMID:14685270 Drosophila Cup is an eIF4E-binding protein that functions in... | REMOVE | Summary: Generic protein binding (Cup with Smaug). Reason: Protein binding is uninformative. The Smaug-Cup interaction recruits Cup to nanos mRNA; its functional consequence is captured by translation repressor activity and negative regulation of translation. Removal does not dispute the interaction. Supporting Evidence: PMID:14685270 Here we demonstrate that Smaug interacts with the Cup protein |
| GO:0005515 protein binding | IPI PMID:14723848 Drosophila cup is an eIF4E binding protein that associates w... | REMOVE | Summary: Generic protein binding (Cup with Me31B). Reason: Protein binding is uninformative. The Cup-Me31B association reflects co-membership of repressive maternal RNPs, which is captured by the P-body and translational repression annotations. Removal does not dispute the interaction. Supporting Evidence: PMID:21937713 This domain associates with the deadenylase complex CAF1-CCR4-NOT and decapping activators |
| GO:0005515 protein binding | IPI PMID:14723848 Drosophila cup is an eIF4E binding protein that associates w... | MODIFY | Summary: Protein binding between Cup and eIF4E1. Reason: Cup binds eIF4E through a canonical YXXXXL motif plus a non-canonical lateral motif; the informative term is eukaryotic initiation factor 4E binding. Proposed replacements: eukaryotic initiation factor 4E binding Supporting Evidence: PMID:14685270 Cup is an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E PMID:14723848 Cup binds the 5'-cap binding translation initiation factor eIF4E through a sequence conserved among eIF4E binding proteins |
| GO:0005515 protein binding | IPI PMID:17277377 nup154 genetically interacts with cup and plays a cell-type-... | REMOVE | Summary: Generic protein binding (Cup with the nucleoporin Nup154). Reason: Protein binding is uninformative and the functional relevance of Cup-Nup154 co-immunoprecipitation is unclear. Removal does not dispute the interaction. Supporting Evidence: PMID:17277377 The two proteins colocalize in vivo and are co-immunoprecipitated from ovarian extracts |
| GO:0005634 nucleus | EXP PMID:15465908 Cup is a nucleocytoplasmic shuttling protein that interacts ... | KEEP AS NON CORE | Summary: Cup can enter the nucleus. Reason: Cup is a nucleocytoplasmic shuttling protein that accumulates in the nucleus when CRM1 export is blocked, but at steady state it is retained in the cytoplasm by eIF4E binding, where its repressor functions are executed. Nuclear localization is real but not the site of its core activity. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cup can enter the nucleus. Reason: Cup is a nucleocytoplasmic shuttling protein that accumulates in the nucleus when CRM1 export is blocked, but at steady state it is retained in the cytoplasm by eIF4E binding, where its repressor functions are executed. Nuclear localization is real but not the site of its core activity. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm |
| GO:0005634 nucleus | IDA PMID:24335285 Human 4E-T represses translation of bound mRNAs and enhances... | KEEP AS NON CORE | Summary: Cup can enter the nucleus. Reason: Cup is a nucleocytoplasmic shuttling protein that accumulates in the nucleus when CRM1 export is blocked, but at steady state it is retained in the cytoplasm by eIF4E binding, where its repressor functions are executed. Nuclear localization is real but not the site of its core activity. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cup can enter the nucleus. Reason: Cup is a nucleocytoplasmic shuttling protein that accumulates in the nucleus when CRM1 export is blocked, but at steady state it is retained in the cytoplasm by eIF4E binding, where its repressor functions are executed. Nuclear localization is real but not the site of its core activity. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:15465908 Cup is a nucleocytoplasmic shuttling protein that interacts ... | ACCEPT | Summary: Cup is a cytoplasmic protein in germline cells. Reason: Cup is predominantly cytoplasmic in nurse cells and oocytes, where it associates with maternal mRNPs and represses translation. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm PMID:9118812 It is strongly associated with large structures in the cytoplasm and perinuclear region of nurse cells |
| GO:0005737 cytoplasm | EXP PMID:17277377 nup154 genetically interacts with cup and plays a cell-type-... | ACCEPT | Summary: Cup is a cytoplasmic protein in germline cells. Reason: Cup is predominantly cytoplasmic in nurse cells and oocytes, where it associates with maternal mRNPs and represses translation. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm PMID:9118812 It is strongly associated with large structures in the cytoplasm and perinuclear region of nurse cells |
| GO:0005737 cytoplasm | EXP PMID:9118812 The Drosophila gene fs(2)cup interacts with otu to define a ... | ACCEPT | Summary: Cup is a cytoplasmic protein in germline cells. Reason: Cup is predominantly cytoplasmic in nurse cells and oocytes, where it associates with maternal mRNPs and represses translation. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm PMID:9118812 It is strongly associated with large structures in the cytoplasm and perinuclear region of nurse cells |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cup is a cytoplasmic protein in germline cells. Reason: Cup is predominantly cytoplasmic in nurse cells and oocytes, where it associates with maternal mRNPs and represses translation. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm PMID:9118812 It is strongly associated with large structures in the cytoplasm and perinuclear region of nurse cells |
| GO:0005737 cytoplasm | IDA PMID:19101615 The molecular chaperone Hsp90 is a component of the cap-bind... | ACCEPT | Summary: Cup is a cytoplasmic protein in germline cells. Reason: Cup is predominantly cytoplasmic in nurse cells and oocytes, where it associates with maternal mRNPs and represses translation. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm PMID:9118812 It is strongly associated with large structures in the cytoplasm and perinuclear region of nurse cells |
| GO:0005737 cytoplasm | IDA PMID:24335285 Human 4E-T represses translation of bound mRNAs and enhances... | ACCEPT | Summary: Cup is a cytoplasmic protein in germline cells. Reason: Cup is predominantly cytoplasmic in nurse cells and oocytes, where it associates with maternal mRNPs and represses translation. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm PMID:9118812 It is strongly associated with large structures in the cytoplasm and perinuclear region of nurse cells |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cup is a cytoplasmic protein in germline cells. Reason: Cup is predominantly cytoplasmic in nurse cells and oocytes, where it associates with maternal mRNPs and represses translation. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm PMID:9118812 It is strongly associated with large structures in the cytoplasm and perinuclear region of nurse cells |
| GO:0005829 cytosol | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | ACCEPT | Summary: Cytosolic localization from a high-throughput YFP-trap localization screen. Reason: Consistent with the many low-throughput observations of cytoplasmic Cup. Supporting Evidence: PMID:15465908 Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm |
| GO:0007143 female meiotic nuclear division | IGI PMID:11060247 Nanos interacts with cup in the female germline of Drosophil... | KEEP AS NON CORE | Summary: cup mutations perturb female meiotic chromosome segregation. Reason: Dominant cup alleles disrupt meiotic chromosome segregation and cup is needed for normal nurse cell and oocyte chromosome morphology. These are downstream consequences of Cup function in the germline cytoplasm rather than a direct role in the meiotic machinery. Supporting Evidence: PMID:9118812 cup mutations dominantly disrupt meiotic chromosome segregation |
| GO:0007297 follicle cell of egg chamber migration | HMP PMID:1783295 Female sterile mutations on the second chromosome of Drosoph... | UNDECIDED | Summary: Follicle cell migration from a large female-sterile mutant screen. Reason: The cited screen paper characterizes hundreds of female-sterile lines; the abstract does not describe a follicle cell migration phenotype for cup, and the full text was not available. A direct role for germline Cup in somatic follicle cell migration is not supported by other literature. Supporting Evidence: PMID:1783295 In 333 lines oogenesis proceeds apparently normally to stage 8 of oogenesis, but morphological defects become often apparent during later stages of oogenesis |
| GO:0007317 regulation of germ plasm oskar mRNA localization | IMP PMID:14691130 Cup-ling oskar RNA localization and translational control. | ACCEPT | Summary: Cup is required for oskar mRNA localization and recruits Barentsz to the oskar RNP. Reason: Cup is a component of the oskar RNP, is required for oskar mRNA localization and recruits the transport factor Barentsz, coupling localization to translational repression. Supporting Evidence: PMID:14691132 cup is required for oskar mRNA localization and is necessary to recruit the plus end-directed microtubule transport factor Barentsz to the complex |
| GO:0007317 regulation of germ plasm oskar mRNA localization | IMP PMID:14691132 Cup is an eIF4E binding protein required for both the transl... | ACCEPT | Summary: Cup is required for oskar mRNA localization and recruits Barentsz to the oskar RNP. Reason: Cup is a component of the oskar RNP, is required for oskar mRNA localization and recruits the transport factor Barentsz, coupling localization to translational repression. Supporting Evidence: PMID:14691132 cup is required for oskar mRNA localization and is necessary to recruit the plus end-directed microtubule transport factor Barentsz to the complex |
| GO:0007319 negative regulation of oskar mRNA translation | IDA PMID:16469699 Bruno acts as a dual repressor of oskar translation, promoti... | ACCEPT | Summary: Cup represses translation of unlocalized oskar mRNA. Reason: Cup is recruited to oskar mRNA by Bruno and inhibits small ribosomal subunit recruitment; Cup lacking the eIF4E-binding motif fails to repress oskar in vivo. Supporting Evidence: PMID:16469699 we directly demonstrate the mechanism proposed for Cup-mediated repression: inhibition of small ribosomal subunit recruitment to oskar mRNA PMID:14723848 Cup is required to repress precocious osk translation |
| GO:0007319 negative regulation of oskar mRNA translation | IMP PMID:14691132 Cup is an eIF4E binding protein required for both the transl... | ACCEPT | Summary: Cup represses translation of unlocalized oskar mRNA. Reason: Cup is recruited to oskar mRNA by Bruno and inhibits small ribosomal subunit recruitment; Cup lacking the eIF4E-binding motif fails to repress oskar in vivo. Supporting Evidence: PMID:16469699 we directly demonstrate the mechanism proposed for Cup-mediated repression: inhibition of small ribosomal subunit recruitment to oskar mRNA PMID:14723848 Cup is required to repress precocious osk translation |
| GO:0008190 eukaryotic initiation factor 4E binding | IDA PMID:25179781 4E-BPs require non-canonical 4E-binding motifs and a lateral... | ACCEPT | Summary: Cup directly binds eIF4E via canonical and non-canonical motifs. Reason: Structural and biochemical studies show bipartite binding of Cup to the dorsal and lateral surfaces of eIF4E. Supporting Evidence: PMID:25179781 the II-AA mutations disrupted the association of eIF4E with CUP, Thor and 4E-T but not with eIF4G PMID:22832024 two separate segments of Cup contact two orthogonal faces of eIF4E |
| GO:0008298 intracellular mRNA localization | IMP PMID:18082158 Squid, Cup, and PABP55B function together to regulate gurken... | KEEP AS NON CORE | Summary: cup mutants mislocalize gurken mRNA. Reason: Cup acts with Squid in localizing and repressing gurken mRNA; this is part of its germline mRNP role but the localization phenotype is secondary to its repressor function. Supporting Evidence: PMID:18082158 display defects in grk mRNA localization and Grk protein accumulation |
| GO:0008582 regulation of synaptic assembly at neuromuscular junction | IMP PMID:26102195 The translational regulator Cup controls NMJ presynaptic ter... | KEEP AS NON CORE | Summary: Zygotic Cup at larval NMJ presynaptic terminals controls bouton morphology. Reason: cup mutant NMJs have satellite boutons; this is a context-specific neuronal role of a translational repressor. Supporting Evidence: PMID:26102195 cup mutant NMJs have strong phenotypes characterized by the presence of small clustered boutons called satellite boutons |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:18082158 Squid, Cup, and PABP55B function together to regulate gurken... | KEEP AS NON CORE | Summary: cup mutants lay dorsalized eggs. Reason: The dorsoventral patterning phenotype is a consequence of Cup-dependent gurken mRNA regulation in the oocyte. Supporting Evidence: PMID:18082158 We show that cup mutants lay dorsalized eggs |
| GO:0017148 negative regulation of translation | IBA GO_REF:0000033 | ACCEPT | Summary: Cup is a translational repressor of specific maternal mRNAs. Reason: Cup represses oskar, nanos and gurken mRNAs by blocking eIF4G recruitment to eIF4E and by eIF4E-independent effector-domain mechanisms. Supporting Evidence: PMID:14685270 Cup is an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E PMID:14685270 Smaug represses translation via a Cup-dependent block in eIF4G recruitment |
| GO:0017148 negative regulation of translation | IMP PMID:18082158 Squid, Cup, and PABP55B function together to regulate gurken... | ACCEPT | Summary: Cup is a translational repressor of specific maternal mRNAs. Reason: Cup represses oskar, nanos and gurken mRNAs by blocking eIF4G recruitment to eIF4E and by eIF4E-independent effector-domain mechanisms. Supporting Evidence: PMID:14685270 Cup is an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E PMID:14685270 Smaug represses translation via a Cup-dependent block in eIF4G recruitment |
| GO:0017148 negative regulation of translation | IPI PMID:14685270 Drosophila Cup is an eIF4E-binding protein that functions in... | ACCEPT | Summary: Cup is a translational repressor of specific maternal mRNAs. Reason: Cup represses oskar, nanos and gurken mRNAs by blocking eIF4G recruitment to eIF4E and by eIF4E-independent effector-domain mechanisms. Supporting Evidence: PMID:14685270 Cup is an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E PMID:14685270 Smaug represses translation via a Cup-dependent block in eIF4G recruitment |
| GO:0030371 translation repressor activity | IMP PMID:37553798 Cup is essential for oskar mRNA translational repression dur... | ACCEPT | Summary: Cup has translation repressor activity. Reason: Cup is sufficient to maintain translational repression of oskar and is the co-repressor in Smaug-dependent nanos repression. Supporting Evidence: PMID:37553798 this suggests that Cup is sufficient to maintain the translational repression of osk mRNA PMID:36951092 The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4-NOT deadenylase |
| GO:0030371 translation repressor activity | TAS PMID:36951092 RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent... | ACCEPT | Summary: Cup has translation repressor activity. Reason: Cup is sufficient to maintain translational repression of oskar and is the co-repressor in Smaug-dependent nanos repression. Supporting Evidence: PMID:37553798 this suggests that Cup is sufficient to maintain the translational repression of osk mRNA PMID:36951092 The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4-NOT deadenylase |
| GO:0030715 oocyte growth in germarium-derived egg chamber | IGI PMID:17277377 nup154 genetically interacts with cup and plays a cell-type-... | KEEP AS NON CORE | Summary: cup and nup154 interact genetically in egg-chamber development. Reason: Oocyte growth defects are a developmental consequence of Cup loss. Supporting Evidence: PMID:17277377 cup, nup154 double mutants exhibit much stronger oogenesis defects than single mutants PMID:9118812 the gene is needed for the oocyte to grow normally by taking up materials transported from the nurse cells |
| GO:0031594 neuromuscular junction | IDA PMID:26102195 The translational regulator Cup controls NMJ presynaptic ter... | KEEP AS NON CORE | Summary: Cup localizes to presynaptic terminals at the larval NMJ. Reason: Zygotic Cup is present in presynaptic boutons; a context-specific location. Supporting Evidence: PMID:26102195 we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs) |
| GO:0032019 mitochondrial cloud | IDA PMID:16887820 Milton controls the early acquisition of mitochondria by Dro... | KEEP AS NON CORE | Summary: Cup is found in the Balbiani body (mitochondrial cloud) of early oocytes. Reason: Germ plasm components associate with the Balbiani body; this is a minor localization of a cytoplasmic RNP protein. Supporting Evidence: PMID:16887820 Organelles and germ plasm components frequently associate with this structure |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IEA GO_REF:0000120 | ACCEPT | Summary: Cup is a component of cytoplasmic RNP granules. Reason: Consistent with its P-body and germline RNP localization. Supporting Evidence: PMID:37553798 Cup has also been identified as a processing body (P-body) component due to its association with two core P-body proteins, Me31B and Trailer Hitch (Tral) |
| GO:0043195 terminal bouton | IDA PMID:26102195 The translational regulator Cup controls NMJ presynaptic ter... | KEEP AS NON CORE | Summary: Cup localizes to presynaptic terminals at the larval NMJ. Reason: Zygotic Cup is present in presynaptic boutons; a context-specific location. Supporting Evidence: PMID:26102195 we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs) |
| GO:0045132 meiotic chromosome segregation | IDA PMID:9118812 The Drosophila gene fs(2)cup interacts with otu to define a ... | KEEP AS NON CORE | Summary: cup mutations perturb female meiotic chromosome segregation. Reason: Dominant cup alleles disrupt meiotic chromosome segregation and cup is needed for normal nurse cell and oocyte chromosome morphology. These are downstream consequences of Cup function in the germline cytoplasm rather than a direct role in the meiotic machinery. Supporting Evidence: PMID:9118812 cup mutations dominantly disrupt meiotic chromosome segregation |
| GO:0045182 translation regulator activity | IDA PMID:14723848 Drosophila cup is an eIF4E binding protein that associates w... | MODIFY | Summary: Translation regulator activity is correct but too general. Reason: Cup acts specifically as a translational repressor; the more precise term is translation repressor activity. Proposed replacements: translation repressor activity Supporting Evidence: PMID:14723848 Cup is required to repress precocious osk translation |
| GO:0045947 negative regulation of translational initiation | IDA PMID:25179781 4E-BPs require non-canonical 4E-binding motifs and a lateral... | ACCEPT | Summary: Cup inhibits translation initiation by displacing eIF4G from eIF4E. Reason: Cup and other 4E-BPs use canonical and non-canonical motifs to dock on eIF4E and displace eIF4G, inhibiting initiation. Supporting Evidence: PMID:25179781 This distinct molecular recognition mode is exploited by 4E-BPs to dock onto eIF4E-eIF4G complexes and effectively displace eIF4G from the dorsal surface of eIF4E PMID:14685270 Cup is an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E |
| GO:0048477 oogenesis | HMP PMID:1783295 Female sterile mutations on the second chromosome of Drosoph... | KEEP AS NON CORE | Summary: Cup is required for oogenesis. Reason: fs(2)cup is a female-sterile gene and cup mutant egg chambers arrest; oogenesis is the developmental context of Cup function rather than its molecular role. Supporting Evidence: PMID:15465908 Cup is required for the correct accumulation and localization of eIF4E within the posterior cytoplasm of developing oocytes |
| GO:0048477 oogenesis | IMP PMID:18082158 Squid, Cup, and PABP55B function together to regulate gurken... | KEEP AS NON CORE | Summary: Cup is required for oogenesis. Reason: fs(2)cup is a female-sterile gene and cup mutant egg chambers arrest; oogenesis is the developmental context of Cup function rather than its molecular role. Supporting Evidence: PMID:15465908 Cup is required for the correct accumulation and localization of eIF4E within the posterior cytoplasm of developing oocytes |
| GO:0070971 endoplasmic reticulum exit site | IDA PMID:16256742 Efficient protein trafficking requires trailer hitch, a comp... | KEEP AS NON CORE | Summary: Cup co-localizes with the Tral RNP near ER exit sites. Reason: Cup is part of the Tral/Me31B RNP that localizes to ER subdomains bordering exit sites; a minor, context-specific localization. Supporting Evidence: PMID:16256742 it is part of a large RNA-protein complex that includes the translation/localization factors Me31B and Cup |
| GO:0071598 neuronal ribonucleoprotein granule | IDA PMID:17178403 Staufen- and FMRP-containing neuronal RNPs are structurally ... | KEEP AS NON CORE | Summary: Cup in neuronal RNP granules. Reason: Cup is present in Staufen/FMRP neuronal RNPs that share P-body components; secondary localization in neurons. Supporting Evidence: PMID:17178403 staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic "P bodies" |
| GO:0140517 protein-RNA adaptor activity | IDA PMID:37553798 Cup is essential for oskar mRNA translational repression dur... | MARK AS OVER ANNOTATED | Summary: Protein-RNA adaptor activity for Cup in oskar repression. Reason: Cup lacks an RNA-binding domain; it is recruited to oskar mRNA by Bruno1 and bridges Bruno1 to eIF4E, forming a Bru1-Cup-eIF4E repressor complex. Its adaptor role links two proteins rather than a protein and an RNA, and is better captured by eIF4E binding plus translation repressor activity. Supporting Evidence: PMID:37553798 For osk mRNA, the current model suggests that Bru1 recruits Cup to the transcript, forming a Bru1-Cup-eIF4E translational repression complex |
| GO:1905536 negative regulation of eukaryotic translation initiation factor 4F complex assembly | IDA PMID:25179781 4E-BPs require non-canonical 4E-binding motifs and a lateral... | ACCEPT | Summary: Cup inhibits eIF4F assembly by competing with eIF4G for eIF4E. Reason: Directly demonstrated for Cup C+NC motifs. Supporting Evidence: PMID:25179781 This distinct molecular recognition mode is exploited by 4E-BPs to dock onto eIF4E-eIF4G complexes and effectively displace eIF4G from the dorsal surface of eIF4E |
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Download this section (compressed HTML)Q: How do the eIF4E-dependent and eIF4E-independent (effector-domain) repression mechanisms of Cup divide the work of silencing oskar, nanos and gurken mRNAs in vivo?
Q: Does Cup nuclear shuttling have a function, for example loading Cup onto mRNPs before export, or is it a consequence of free Cup lacking eIF4E?
Experiment: Express endogenous-locus Cup variants lacking the canonical and non-canonical eIF4E-binding motifs, or lacking the effector domain, and measure Oskar protein, oskar poly(A) tail length and P-body recruitment in stage 1-8 egg chambers.
Hypothesis: The Cup effector domain, independently of eIF4E binding, is sufficient to repress and deadenylate oskar mRNA in the oocyte.
Type: endogenous structure-function rescue
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