Ran (Ran10A, CG1404) is the single Ran-family small GTPase of Drosophila melanogaster. It cycles between a GTP-bound form, generated in the nucleus by the chromatin-bound exchange factor RCC1, and a GDP-bound form produced in the cytoplasm by RanGAP-stimulated hydrolysis. The resulting RanGTP gradient across the nuclear envelope sets the direction of nucleocytoplasmic transport: RanGTP releases NLS cargo from importins in the nucleus and loads cargo onto exportins such as CRM1/Embargoed for export of proteins and RNPs. After nuclear envelope breakdown, chromatin-proximal RanGTP promotes spindle assembly by freeing spindle factors from importins; fly Ran localizes around mitotic and meiotic spindles, is required for spindle assembly, chromosome alignment and segregation in syncytial embryos, and contributes to pole organisation of the acentrosomal oocyte spindle and to sperm-aster microtubules needed for pronuclear fusion. RanGTP binds the RA domains of Canoe and is needed for Mud recruitment to cortical Pins in the Pins(TPR)/Mud/dynein spindle orientation pathway. In oogenesis Ran regulates condensation of Nup358-containing nucleoporin granules and biogenesis of annulate lamellae and nuclear pores. Ran is essential for viability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000055 ribosomal large subunit export from nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Ribosomal large subunit export from nucleus. Reason: RanGTP is a required component of the exportin (CRM1/XPO1) export complexes that carry pre-ribosomal subunits out of the nucleus, so Ran does part of the work of the step. No fly experiment, but the function is a direct consequence of the conserved RanGTP-exportin mechanism; one of many cargo classes of a general transport GTPase, hence non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000632582 SUPPORTS TRANSFER Node seeded by yeast/human Ran ribosome-export data; RanGTP-dependent exportin cargo release is conserved in fly. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0000056 ribosomal small subunit export from nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Ribosomal small subunit export from nucleus. Reason: RanGTP is a required component of the exportin (CRM1/XPO1) export complexes that carry pre-ribosomal subunits out of the nucleus, so Ran does part of the work of the step. No fly experiment, but the function is a direct consequence of the conserved RanGTP-exportin mechanism; one of many cargo classes of a general transport GTPase, hence non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000632582 SUPPORTS TRANSFER Node seeded by yeast/human Ran ribosome-export data; RanGTP-dependent exportin cargo release is conserved in fly. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0000132 establishment of mitotic spindle orientation | IGI PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | ACCEPT | Summary: Establishment of mitotic spindle orientation (genetic interaction with dlg1). Reason: Full text: dlg1; double RNAi was more severe than ran alone, placing Ran in the Pins(TPR) branch parallel to the Dlg/Linker branch. Consistent with the direct Canoe RA-RanGTP binding and Ran requirement for Mud recruitment. Supporting Evidence: PMID:22024168 double RNAi knockdowns of ran and the PinsLINKER pathway component dlg led to a more severe spindle orientation phenotype than ran RNAi alone PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0000132 establishment of mitotic spindle orientation | IGI PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | ACCEPT | Summary: Establishment of mitotic spindle orientation (genetic interaction with canoe). Reason: Full text: canoe; double RNAi resembled canoe alone, placing Ran in the Canoe pathway. Consistent with the direct Canoe RA-RanGTP binding and Ran requirement for Mud recruitment. Supporting Evidence: PMID:22024168 we performed double RNAi knockdowns of canoe and ran in S2 cells expressing Ed:PinsTPR+LINKER and found that spindle orientation was reduced similar to canoe RNAi alone PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0000132 establishment of mitotic spindle orientation | IMP PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | ACCEPT | Summary: Establishment of mitotic spindle orientation (ran RNAi in S2 induced-polarity assay). Reason: Full text: ran RNAi reduced Pins(TPR)-mediated spindle orientation and abolished Mud recruitment to Pins crescents, while RanGTP binds Canoe RA domains directly. Ran therefore does mechanistic work in the pathway (GTP-state-dependent effector engagement of Canoe), not only being required. Supporting Evidence: PMID:22024168 we performed RNAi knockdown of endogenous Ran in S2 cells expressing Ed:PinsTPR+LINKER and found that spindle orientation was reduced PMID:22024168 Similarly, Mud failed to localize to Ed:PinsTPR+LINKER crescents after ran RNAi PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0000212 meiotic spindle organization | IMP PMID:22100918 RanGTP is required for meiotic spindle organization and the ... | KEEP AS NON CORE | Summary: Meiotic spindle organization (dominant-negative RanT24N in oocytes). Reason: Full text: RanT24N oocytes assemble acentrosomal spindles but show defects in tapering of microtubules at spindle poles; RanGTP was not essential for meiotic spindle assembly. A genuine but modest role in organisation of the meiotic spindle, consistent with RanGTP releasing spindle factors such as TACC and Mars; non-core relative to transport. Supporting Evidence: PMID:22100918 the most important function of the Ran pathway in spindle assembly appears to be in the tapering of microtubules at the spindle poles PMID:22100918 Females expressing a dominant-negative form of Ran have fertility defects |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: GTPase activity; Ran hydrolyses GTP (RanGAP-stimulated) to switch from the nuclear GTP-bound to the cytoplasmic GDP-bound state. Reason: Ran is a canonical Ran-family small GTPase; its GTP/GDP cycle is the basis of transport directionality and of RanGTP signalling in mitosis. GTP-state-dependent effector binding is shown for fly Ran (Canoe RA domains bind GMPPNP- but not GDP-loaded Ran), and GTP-locked (Q69L/L43E) and GDP-locked (T24N) fly alleles behave as expected for a GTPase switch. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000632582 SUPPORTS TRANSFER Ran-family node seeded by human RAN, yeast GSP1 and S. pombe spi1; fly Ran is inside the clade and retains all G-box motifs. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state file:DROME/Ran/Ran-uniprot.txt Belongs to the small GTPase superfamily. Ran family. file:DROME/Ran/Ran-uniprot.txt InterPro; IPR002041; Ran_GTPase. PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: GTPase activity; Ran hydrolyses GTP (RanGAP-stimulated) to switch from the nuclear GTP-bound to the cytoplasmic GDP-bound state. Reason: Ran is a canonical Ran-family small GTPase; its GTP/GDP cycle is the basis of transport directionality and of RanGTP signalling in mitosis. GTP-state-dependent effector binding is shown for fly Ran (Canoe RA domains bind GMPPNP- but not GDP-loaded Ran), and GTP-locked (Q69L/L43E) and GDP-locked (T24N) fly alleles behave as expected for a GTPase switch. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state file:DROME/Ran/Ran-uniprot.txt Belongs to the small GTPase superfamily. Ran family. file:DROME/Ran/Ran-uniprot.txt InterPro; IPR002041; Ran_GTPase. PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0003924 GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: GTPase activity; Ran hydrolyses GTP (RanGAP-stimulated) to switch from the nuclear GTP-bound to the cytoplasmic GDP-bound state. Reason: Ran is a canonical Ran-family small GTPase; its GTP/GDP cycle is the basis of transport directionality and of RanGTP signalling in mitosis. GTP-state-dependent effector binding is shown for fly Ran (Canoe RA domains bind GMPPNP- but not GDP-loaded Ran), and GTP-locked (Q69L/L43E) and GDP-locked (T24N) fly alleles behave as expected for a GTPase switch. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state file:DROME/Ran/Ran-uniprot.txt Belongs to the small GTPase superfamily. Ran family. file:DROME/Ran/Ran-uniprot.txt InterPro; IPR002041; Ran_GTPase. PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0005515 protein binding | IPI PMID:12653959 Tamo selectively modulates nuclear import in Drosophila. | REMOVE | Summary: Protein binding with Tamo (Q9W1A4). Reason: Bare protein binding is uninformative. The Tamo-Ran interaction (abstract only) places Ran among nuclear import machinery contacts of Tamo, which is captured by the protein import into nucleus rows. Supporting Evidence: PMID:12653959 In addition Tamo binds the Ras family small GTPase, Ran. |
| GO:0005515 protein binding | IPI PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | REMOVE | Summary: Protein binding with Canoe (FBgn0259212). Reason: Bare protein binding is uninformative. The interaction is real and GTP dependent (RanGTP is the ligand of the Canoe RA domains), but Ran here acts as a GTPase whose GTP-bound state is read by an effector; that is captured by GTPase activity and by the spindle orientation process, and no informative Ran-side binding term applies. Supporting Evidence: PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0005525 GTP binding | IDA PMID:12121620 Ran localizes around the microtubule spindle in vivo during ... | ACCEPT | Summary: GTP binding. Reason: Ran binds GTP; GTP-bound Ran is the active form recognised by transport receptors and by Canoe RA domains. The IDA paper (abstract only) used a GTP-locked RanL43E allele; the claim is fully consistent with family biochemistry. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. file:DROME/Ran/Ran-uniprot.txt InterPro; IPR002041; Ran_GTPase. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTP binding. Reason: Ran binds GTP; GTP-bound Ran is the active form recognised by transport receptors and by Canoe RA domains. The IDA paper (abstract only) used a GTP-locked RanL43E allele; the claim is fully consistent with family biochemistry. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. file:DROME/Ran/Ran-uniprot.txt InterPro; IPR002041; Ran_GTPase. |
| GO:0005634 nucleus | EXP PMID:12121620 Ran localizes around the microtubule spindle in vivo during ... | ACCEPT | Summary: Nucleus; RanGTP is concentrated in the interphase nucleus. Reason: Ran is nuclear in interphase (RCC1 on chromatin generates nuclear RanGTP); directly observed for fly Ran in oocytes/embryos. Supporting Evidence: PMID:22100918 Ran was nuclear during interphase and then overlapped with the spindle during metaphase and anaphase file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0005634 nucleus | IDA PMID:22100918 RanGTP is required for meiotic spindle organization and the ... | ACCEPT | Summary: Nucleus; RanGTP is concentrated in the interphase nucleus. Reason: Ran is nuclear in interphase (RCC1 on chromatin generates nuclear RanGTP); directly observed for fly Ran in oocytes/embryos. Supporting Evidence: PMID:22100918 Ran was nuclear during interphase and then overlapped with the spindle during metaphase and anaphase file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus; RanGTP is concentrated in the interphase nucleus. Reason: Ran is nuclear in interphase (RCC1 on chromatin generates nuclear RanGTP); directly observed for fly Ran in oocytes/embryos. Supporting Evidence: PMID:22100918 Ran was nuclear during interphase and then overlapped with the spindle during metaphase and anaphase file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0005634 nucleus | NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle. | ACCEPT | Summary: Nucleus; RanGTP is concentrated in the interphase nucleus. Reason: Ran is nuclear in interphase (RCC1 on chromatin generates nuclear RanGTP); directly observed for fly Ran in oocytes/embryos. Supporting Evidence: PMID:22100918 Ran was nuclear during interphase and then overlapped with the spindle during metaphase and anaphase file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0005635 nuclear envelope | EXP PMID:12121620 Ran localizes around the microtubule spindle in vivo during ... | KEEP AS NON CORE | Summary: Nuclear envelope. Reason: UniProt records nuclear envelope localization from PMID:12121620 (abstract only, cannot inspect images). Ran transits the envelope via pores and RanGAP/RanBP2 sit at the cytoplasmic face, so an envelope signal is plausible; it is peripheral to the core nucleus/cytoplasm shuttling and is retained as non-core, deferring to the curator. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Nucleus envelope {ECO:0000269|PubMed:12121620} |
| GO:0005635 nuclear envelope | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear envelope. Reason: UniProt records nuclear envelope localization from PMID:12121620 (abstract only, cannot inspect images). Ran transits the envelope via pores and RanGAP/RanBP2 sit at the cytoplasmic face, so an envelope signal is plausible; it is peripheral to the core nucleus/cytoplasm shuttling and is retained as non-core, deferring to the curator. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Nucleus envelope {ECO:0000269|PubMed:12121620} |
| GO:0005643 nuclear pore | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Nuclear pore (part_of). Reason: Ran is a soluble shuttling GTPase that passes through nuclear pores with transport receptors (and is imported by NTF2); it is not a structural subunit of the nuclear pore complex. part_of nuclear pore overstates a transient transit location. The sources (rat Ran, a trypanosome Ran) probably reflect pore-associated signal in fractionation or imaging. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000632582 SUPPORTS SOURCE BUT NOT TARGET Ran is at pores only transiently as cargo of the transport machinery; part_of NPC is not inherited as a structural relation. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state PMID:17287812 organized cycle of interactions between cargoes, carriers and the Ran GTPase |
| GO:0005737 cytoplasm | EXP PMID:12121620 Ran localizes around the microtubule spindle in vivo during ... | ACCEPT | Summary: Cytoplasm; RanGDP is the cytoplasmic form. Reason: Ran shuttles and its GDP-bound form is cytoplasmic; after nuclear envelope breakdown fly Ran redistributes around the spindle in the cytoplasm. Cytoplasm is as precise as warranted for a soluble shuttling GTPase. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state PMID:12121620 localize around the spindle |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm; RanGDP is the cytoplasmic form. Reason: Ran shuttles and its GDP-bound form is cytoplasmic; after nuclear envelope breakdown fly Ran redistributes around the spindle in the cytoplasm. Cytoplasm is as precise as warranted for a soluble shuttling GTPase. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000632582 SUPPORTS TRANSFER Node includes fly Ran itself (FB:FBgn0020255) among sources; cytoplasmic RanGDP is conserved. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state PMID:12121620 localize around the spindle |
| GO:0005737 cytoplasm | IDA PMID:12653959 Tamo selectively modulates nuclear import in Drosophila. | ACCEPT | Summary: Cytoplasm; RanGDP is the cytoplasmic form. Reason: Ran shuttles and its GDP-bound form is cytoplasmic; after nuclear envelope breakdown fly Ran redistributes around the spindle in the cytoplasm. Cytoplasm is as precise as warranted for a soluble shuttling GTPase. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state PMID:12121620 localize around the spindle |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm; RanGDP is the cytoplasmic form. Reason: Ran shuttles and its GDP-bound form is cytoplasmic; after nuclear envelope breakdown fly Ran redistributes around the spindle in the cytoplasm. Cytoplasm is as precise as warranted for a soluble shuttling GTPase. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state PMID:12121620 localize around the spindle |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: Spindle. Reason: Fly Ran localizes around/overlapping the spindle in mitotic embryos and in meiotic oocytes; spindle covers both and is as precise as an electronic SubCell mapping can be. Mitotic spindle is also captured by the IDA rows. Supporting Evidence: PMID:12121620 localize around the spindle PMID:22100918 Ran was nuclear during interphase and then overlapped with the spindle during metaphase and anaphase PMID:22100918 wild-type Ran surrounds the metaphase I spindle |
| GO:0005938 cell cortex | IDA PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | MARK AS OVER ANNOTATED | Summary: Cell cortex. Reason: Full text read: cortical Ran was observed only when Flag:Ran was recruited to cortical crescents of an engineered transmembrane fusion (Ed:GFP:CnoRA) in aggregated S2 cells, demonstrating CanoeRA-dependent recruitment rather than a native cortical location of Ran. Endogenous Ran localization at the neuroblast cortex was not shown. The data support Canoe binding and the spindle orientation role, not cell cortex as a normal location. Supporting Evidence: PMID:22024168 Ed:GFP or Ed:GFP:CnoRA was used to form cortical crescents by cell aggregation, and the localization of Flag:Ran was visualized in mitotic cells. |
| GO:0006606 protein import into nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Protein import into nucleus. Reason: Core Ran function: RanGTP binding releases NLS cargo from importin beta in the nucleus and the importin-RanGTP complex recycles to the cytoplasm. Fly evidence is consistent (Tamo, a Dorsal import modulator, binds Ran). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000632582 SUPPORTS TRANSFER Ran-family node with human, mouse and yeast seeds; conserved core function. Supporting Evidence: PMID:22100918 Once inside the nucleus, RanGTP binds importin Ξ², releasing importin Ξ± and NLS containing proteins file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport PMID:17287812 organized cycle of interactions between cargoes, carriers and the Ran GTPase |
| GO:0006611 protein export from nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Protein export from nucleus. Reason: Core Ran function: export receptors (CRM1/emb in flies) load NES cargo only together with RanGTP; GTP hydrolysis in the cytoplasm releases it. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000632582 SUPPORTS TRANSFER Node seeded by human RAN; RanGTP-dependent export is conserved. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0006611 protein export from nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Protein export from nucleus. Reason: Core Ran function: export receptors (CRM1/emb in flies) load NES cargo only together with RanGTP; GTP hydrolysis in the cytoplasm releases it. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0006886 intracellular protein transport | TAS PMID:12121620 Ran localizes around the microtubule spindle in vivo during ... | MODIFY | Summary: Intracellular protein transport. Reason: Correct but general: Ran drives protein transport specifically between nucleus and cytoplasm. Both specific descendants are supported and already carried by the gene (protein import into nucleus, protein export from nucleus). Proposed replacements: protein import into nucleus protein export from nucleus Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport PMID:22100918 Once inside the nucleus, RanGTP binds importin Ξ², releasing importin Ξ± and NLS containing proteins |
| GO:0006913 nucleocytoplasmic transport | IEA GO_REF:0000002 | ACCEPT | Summary: Nucleocytoplasmic transport. Reason: Ran governs directionality of nucleocytoplasmic transport for proteins and RNAs in both directions; for a general transport GTPase this umbrella term is an accurate statement of the core process. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport file:DROME/Ran/Ran-uniprot.txt InterPro; IPR002041; Ran_GTPase. |
| GO:0007346 regulation of mitotic cell cycle | IDA PMID:12121620 Ran localizes around the microtubule spindle in vivo during ... | MARK AS OVER ANNOTATED | Summary: Regulation of mitotic cell cycle. Reason: The paper (abstract only) reports localization of Ran pathway components around the spindle, supporting a role in spindle assembly; it does not report a regulatory effect on mitotic cell-cycle progression. Ran is required for multiple mitotic steps (PMID:16481399), but "regulation of mitotic cell cycle" is a vague, indirect description of a spindle-assembly role. Not removed because the full text is unavailable. Supporting Evidence: PMID:12121620 localize around the spindle PMID:16481399 Ran is required before metaphase for spindle assembly and chromosome alignment |
| GO:0016973 poly(A)+ mRNA export from nucleus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Poly(A)+ mRNA export from nucleus. Reason: Seeded only by yeast (S. pombe spi1, S. cerevisiae GSP1), where Ran mutants block mRNA export. In metazoa bulk mRNA export is mediated by NXF1/NXT1 (sbr/Nxt1 in Drosophila) and is largely Ran independent; Ran effects on mRNA export are indirect or limited to specific exportin-dependent mRNAs. Transfer to fly Ran is not well supported. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PomBase:SPBC1289.03c SUPPORTS SOURCE BUT NOT TARGET Yeast-only seeds; metazoan bulk mRNA export uses the Ran-independent NXF1 pathway. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport file:DROME/Ran/Ran-deep-research-manual.md In metazoa bulk mRNA export uses NXF1/NXT1 (sbr/Nxt1 in flies) and is largely Ran |
| GO:0032880 regulation of protein localization | IMP PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | MODIFY | Summary: Regulation of protein localization (ran RNAi blocks Mud recruitment to cortical Pins crescents). Reason: Correct but general and the sign is known: full text shows that after ran RNAi Mud fails to localize to cortical Pins(TPR) crescents, so Ran promotes recruitment of Mud to the cell cortex. The specific supported descendant is positive regulation of protein localization to cell cortex. Proposed replacements: positive regulation of protein localization to cell cortex Supporting Evidence: PMID:22024168 Similarly, Mud failed to localize to Ed:PinsTPR+LINKER crescents after ran RNAi PMID:22024168 We conclude that the Canoe RA domains can interact directly with GTP-loaded Ran. |
| GO:0042564 NLS-dependent protein nuclear import complex | NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle. | REMOVE | Summary: NLS-dependent protein nuclear import complex (part_of). Reason: GO:0042564 is the importin alpha/beta heterodimer that carries NLS cargo. Ran is not a subunit: RanGTP binding to importin beta in the nucleus dissociates this complex and releases cargo. The cited review (abstract only) describes the Ran GTPase as a separate player in the cycle. The row asserts a complex membership that the mechanism contradicts. Supporting Evidence: PMID:22100918 Once inside the nucleus, RanGTP binds importin Ξ², releasing importin Ξ± and NLS containing proteins PMID:17287812 organized cycle of interactions between cargoes, carriers and the Ran GTPase |
| GO:0043243 positive regulation of protein-containing complex disassembly | NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle. | KEEP AS NON CORE | Summary: Positive regulation of protein-containing complex disassembly. Reason: Mechanistically accurate: RanGTP binding to importin beta dissociates importin-cargo complexes in the nucleus (and RanBP1/RanGAP-driven hydrolysis dissociates export complexes). It is a component of the transport mechanism rather than an independent role, hence non-core. Supporting Evidence: PMID:22100918 Once inside the nucleus, RanGTP binds importin Ξ², releasing importin Ξ± and NLS containing proteins |
| GO:0051168 nuclear export | NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle. | ACCEPT | Summary: Nuclear export. Reason: RanGTP is the obligatory cofactor of export receptors for protein and RNA export. Supporting Evidence: file:DROME/Ran/Ran-uniprot.txt compartment and ensures the directionality of the transport file:DROME/Ran/Ran-uniprot.txt Switches between a cytoplasmic GDP- and a nuclear GTP-bound state |
| GO:0051292 nuclear pore complex assembly | IMP PMID:31626769 Nuclear Pores Assemble from Nucleoporin Condensates During O... | KEEP AS NON CORE | Summary: Nuclear pore complex assembly (oocyte annulate lamellae/NPC biogenesis). Reason: Full text: dominant-negative RanT24N reduced Nup358 condensates and annulate lamellae, RanQ69L augmented them; the proposed mechanism is Ran-regulated release of Nups from nuclear transport receptors, so Ran does part of the regulatory work of pore biogenesis. A context-specific role in oogenesis, non-core. Supporting Evidence: PMID:31626769 RanT24N expression reduced both AL and Nup358 condensates PMID:31626769 Ran-regulated NTR chaperoning could spatially control Nup condensation in vivo, as a prerequisite for AL biogenesis |
| GO:0072686 mitotic spindle | IDA PMID:22100918 RanGTP is required for meiotic spindle organization and the ... | ACCEPT | Summary: Colocalizes with mitotic spindle. Reason: Ran overlapped with the spindle in metaphase and anaphase (full text); colocalizes_with is an appropriate qualifier for a diffuse spindle-region signal. Supporting Evidence: PMID:22100918 Ran was nuclear during interphase and then overlapped with the spindle during metaphase and anaphase |
| GO:1990498 mitotic spindle microtubule | IDA PMID:12121620 Ran localizes around the microtubule spindle in vivo during ... | MODIFY | Summary: Mitotic spindle microtubule. Reason: The abstract reports that Ran and RanL43E "localize around the spindle" in syncytial embryos, i.e. a spindle-region (chromatin-proximal) pool rather than binding along spindle microtubules. Full text not available to us; mitotic spindle is the term the reported observation supports. Kept in the CC aspect. Proposed replacements: mitotic spindle Supporting Evidence: PMID:12121620 localize around the spindle |
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Download this section (compressed HTML)Q: Should fly Ran carry a mitotic spindle assembly annotation (Silverman-Gavrila and Wilde 2006, PMID:16481399), given that RanGTP acts by releasing spindle assembly factors from importins rather than by building the spindle itself?
Q: Is the Canoe RA domain-RanGTP interaction required in neuroblasts in vivo, and does RanGTP at the neuroblast cortex arise from a chromatin-derived gradient or a local pool?
Q: Does fly Ran contribute directly to bulk poly(A)+ mRNA export, or only to export of specific exportin-dependent RNAs?
Experiment: Express a Canoe RA-domain mutant that cannot bind RanGTP in canoe mutant larval neuroblasts and score Mud cortical recruitment and spindle orientation, to test the S2-cell model in vivo.
Experiment: Image a RanGTP FRET sensor in syncytial embryos and oocytes to map RanGTP around mitotic and acentrosomal meiotic spindles.
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