pins (Partner of Inscuteable, also Rapsynoid) encodes the Drosophila GPSM/LGN-family scaffold protein, built from N-terminal tetratricopeptide repeats (TPRs) and three C-terminal GoLoco motifs. Through its GoLoco motifs Pins binds GDP-bound Galphai (and Galphao), acting as a guanine nucleotide dissociation inhibitor that anchors it to the cell cortex and frees Gbetagamma. Its TPR domain is held in an autoinhibited closed state that Galphai binding opens, allowing direct binding of Inscuteable, Mud (NuMA), and Canoe. In dividing neuroblasts and sensory organ precursor cells Pins forms an apical (or anterior) cortical crescent with Galphai and Insc, and couples this polarity to mitotic spindle orientation by recruiting Mud and dynein-based pulling forces, contributing to unequal daughter size and to asymmetric segregation of fate determinants.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000132 establishment of mitotic spindle orientation | IBA GO_REF:0000033 | ACCEPT | Summary: Pins orients the mitotic spindle by recruiting Mud/NuMA to its cortical crescent. Reason: Core, well-established process for Pins; supported by direct Pins-Mud binding, induced-polarity assays, and loss-of-function phenotypes, and phylogenetically conserved with LGN/GPR-1/2. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:22024168 activate the Pins/Mud/dynein spindle orientation pathway |
| GO:0000132 establishment of mitotic spindle orientation | IDA PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | ACCEPT | Summary: Pins orients the mitotic spindle by recruiting Mud/NuMA to its cortical crescent. Reason: Core, well-established process for Pins; supported by direct Pins-Mud binding, induced-polarity assays, and loss-of-function phenotypes, and phylogenetically conserved with LGN/GPR-1/2. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:22024168 activate the Pins/Mud/dynein spindle orientation pathway |
| GO:0000132 establishment of mitotic spindle orientation | IMP PMID:12571286 A mouse homologue of Drosophila pins can asymmetrically loca... | ACCEPT | Summary: Pins orients the mitotic spindle by recruiting Mud/NuMA to its cortical crescent. Reason: Core, well-established process for Pins; supported by direct Pins-Mud binding, induced-polarity assays, and loss-of-function phenotypes, and phylogenetically conserved with LGN/GPR-1/2. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:22024168 activate the Pins/Mud/dynein spindle orientation pathway |
| GO:0000132 establishment of mitotic spindle orientation | IMP PMID:21074723 The Fz-Dsh planar cell polarity pathway induces oriented cel... | ACCEPT | Summary: Pins orients the mitotic spindle by recruiting Mud/NuMA to its cortical crescent. Reason: Core, well-established process for Pins; supported by direct Pins-Mud binding, induced-polarity assays, and loss-of-function phenotypes, and phylogenetically conserved with LGN/GPR-1/2. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:22024168 activate the Pins/Mud/dynein spindle orientation pathway |
| GO:0001965 G-protein alpha-subunit binding | IBA GO_REF:0000033 | ACCEPT | Summary: Pins GoLoco motifs bind Galphai subunits. Reason: Galphai binding by the GoLoco motifs is a defining biochemical activity of Pins, shown directly in fly and conserved across the GPSM family. Supporting Evidence: PMID:17726110 Galphai binds to the first of three Pins GoLoco motifs to recruit Pins PMID:10875939 interacts in a two-hybrid assay with the signal transduction protein Galpha(i) |
| GO:0005092 GDP-dissociation inhibitor activity | IBA GO_REF:0000033 | ACCEPT | Summary: GoLoco motifs act as guanine nucleotide dissociation inhibitors for Galphai. Reason: GoLoco proteins are canonical Galpha GDIs; genetic data show Pins and Loco together release free Gbetagamma in neuroblasts, consistent with GDI function. Supporting Evidence: PMID:15937221 Loco and Pins act synergistically to release free Gbetagamma in neuroblasts |
| GO:0005515 protein binding | IPI PMID:16617104 Dual roles for the trimeric G protein Go in asymmetric cell ... | MODIFY | Summary: Pins interacts with Galphao (Go) in SOP asymmetric division. Reason: The partner is a heterotrimeric G-protein alpha subunit, so the informative term is G-protein alpha-subunit binding. Proposed replacements: G-protein alpha-subunit binding Supporting Evidence: PMID:16617104 Go is shown to interact with Pins |
| GO:0005515 protein binding | IPI PMID:16648843 The NuMA-related Mud protein binds Pins and regulates spindl... | MODIFY | Summary: Pins directly binds Mud (NuMA). Reason: Pins binds Mud directly through its TPR domain and recruits it to the apical cortex, i.e. it acts as a cortical adaptor; protein binding is uninformative. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:16648843 Pins directly binds, and coimmunoprecipitates with, the NuMA-related Mushroom body defect (Mud) protein |
| GO:0005515 protein binding | IPI PMID:17726110 Galphai generates multiple Pins activation states to link co... | MODIFY | Summary: Pins binds Galphai via GoLocos and Mud via its TPR domain. Reason: The paper characterizes direct Galphai binding to the Pins GoLoco motifs (and Galphai-gated Mud binding); the informative MF is G-protein alpha-subunit binding. Proposed replacements: G-protein alpha-subunit binding Supporting Evidence: PMID:17726110 Galphai and Mud bind cooperatively to the Pins GoLocos 2/3 and tetratricopeptide repeat domains |
| GO:0005515 protein binding | IPI PMID:17726110 Galphai generates multiple Pins activation states to link co... | MODIFY | Summary: Pins binds Galphai via GoLocos and Mud via its TPR domain. Reason: The paper characterizes direct Galphai binding to the Pins GoLoco motifs (and Galphai-gated Mud binding); the informative MF is G-protein alpha-subunit binding. Proposed replacements: G-protein alpha-subunit binding Supporting Evidence: PMID:17726110 Galphai and Mud bind cooperatively to the Pins GoLocos 2/3 and tetratricopeptide repeat domains |
| GO:0005515 protein binding | IPI PMID:38944040 Next-generation Drosophila protein interactome map and its f... | REMOVE | Summary: High-throughput AP-MS interaction from the DPIM2 interactome. Reason: Bare protein binding from a high-throughput AP-MS screen adds no functional information; removal does not imply the interaction is false. Pins functional partners are captured by more specific terms. Supporting Evidence: PMID:38944040 established from affinity purification-mass spectrometry of 5,805 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Pins is cytoplasmic outside the cortical crescent. Reason: Mapped from UniProt subcellular location; Pins is cytoplasmic in interphase but its functional location is the cell cortex. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Pins is recruited to the plasma membrane/cortex via myristoylated Galphai. Reason: Consistent with Galphai-dependent cortical recruitment of Pins; cortex is the functional site. Supporting Evidence: PMID:17726110 to recruit Pins to the apical cortex |
| GO:0005938 cell cortex | IBA GO_REF:0000033 | ACCEPT | Summary: Pins localizes to the cell cortex. Reason: Directly observed cortical localization, conserved in LGN orthologues. Supporting Evidence: PMID:22024168 The Canoe-Pins(TPR) interaction recruits Canoe to the cell cortex PMID:16377571 induce cortical polarization of Pins/Galphai in Drosophila neuroblasts |
| GO:0005938 cell cortex | IDA PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | ACCEPT | Summary: Pins localizes to the cell cortex. Reason: Directly observed cortical localization, conserved in LGN orthologues. Supporting Evidence: PMID:22024168 The Canoe-Pins(TPR) interaction recruits Canoe to the cell cortex PMID:16377571 induce cortical polarization of Pins/Galphai in Drosophila neuroblasts |
| GO:0007405 neuroblast proliferation | IMP PMID:16142234 Induction of tumor growth by altered stem-cell asymmetric di... | KEEP AS NON CORE | Summary: pins mutant neuroblast tissue overproliferates after transplantation. Reason: The tumour phenotype is an indirect consequence of disrupted asymmetric division rather than a direct role of Pins in proliferation control. Supporting Evidence: PMID:16142234 raps (also called pins), mira, numb or pros grew to more than 100 times their initial size |
| GO:0008356 asymmetric cell division | IDA PMID:20194641 The interphase microtubule aster is a determinant of asymmet... | ACCEPT | Summary: Pins is required for asymmetric cell division. Reason: Classic genetic and imaging evidence that Pins controls asymmetric division of neuroblasts and SOP cells. Supporting Evidence: PMID:10875939 Raps is a novel protein involved in the control of asymmetric divisions of neuroblasts PMID:12571286 Pins acts to stabilize the apical complex during neuroblast divisions |
| GO:0008356 asymmetric cell division | IMP PMID:10875939 Rapsynoid/partner of inscuteable controls asymmetric divisio... | ACCEPT | Summary: Pins is required for asymmetric cell division. Reason: Classic genetic and imaging evidence that Pins controls asymmetric division of neuroblasts and SOP cells. Supporting Evidence: PMID:10875939 Raps is a novel protein involved in the control of asymmetric divisions of neuroblasts PMID:12571286 Pins acts to stabilize the apical complex during neuroblast divisions |
| GO:0008356 asymmetric cell division | IMP PMID:12571286 A mouse homologue of Drosophila pins can asymmetrically loca... | ACCEPT | Summary: Pins is required for asymmetric cell division. Reason: Classic genetic and imaging evidence that Pins controls asymmetric division of neuroblasts and SOP cells. Supporting Evidence: PMID:10875939 Raps is a novel protein involved in the control of asymmetric divisions of neuroblasts PMID:12571286 Pins acts to stabilize the apical complex during neuroblast divisions |
| GO:0019904 protein domain specific binding | IPI PMID:22024168 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle... | KEEP AS NON CORE | Summary: The Pins TPR domain is bound directly by Canoe. Note the direction mismatch, the paper describes Canoe binding a domain of Pins, whereas the annotation asserts that Pins binds a specific domain of its partner. Reason: Accurate domain-mediated interaction, but it describes an interaction rather than Pins' scaffolding activity; kept as non-core in deference to the FlyBase IPI curation despite the direction mismatch. Supporting Evidence: PMID:22024168 directly binds the Partner of Inscuteable (Pins) tetratricopeptide repeat (TPR) domain |
| GO:0030695 GTPase regulator activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based GTPase regulator activity for the GoLoco motifs. Reason: Correct but too general; GoLoco motifs act specifically as Galpha GDP-dissociation inhibitors. Proposed replacements: GDP-dissociation inhibitor activity Supporting Evidence: PMID:15937221 Loco and Pins act synergistically to release free Gbetagamma in neuroblasts |
| GO:0045167 asymmetric protein localization involved in cell fate determination | TAS PMID:12185850 Mechanisms of spindle positioning: focus on flies and worms. | KEEP AS NON CORE | Summary: Pins contributes to asymmetric localization of fate determinants. Reason: Pins stabilizes the apical complex that directs basal determinant localization, but its primary role is in polarity/spindle coupling; the determinant localization role is partially redundant and downstream. Supporting Evidence: PMID:12571286 Pins acts to stabilize the apical complex during neuroblast divisions |
| GO:0045175 basal protein localization | TAS PMID:11117748 The tumour-suppressor genes lgl and dlg regulate basal prote... | KEEP AS NON CORE | Summary: Apical complex activity directs basal protein targeting. Reason: The cited paper shows the apical complex targets determinants basally while lgl/dlg mediate targeting; Pins contribution is indirect via apical complex stability. Supporting Evidence: PMID:11117748 an apical protein complex orients the mitotic spindle and targets determinants of cell fate to the basal cortex |
| GO:0045179 apical cortex | IDA PMID:15937221 Locomotion defects, together with Pins, regulates heterotrim... | ACCEPT | Summary: Pins forms an apical cortical crescent in neuroblasts. Reason: Repeatedly observed apical localization of Pins in neuroblasts. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:28712722 sequentially enriches Rok and Protein Kinase N (Pkn) on the apical neuroblast cortex |
| GO:0045179 apical cortex | IDA PMID:16377571 Microtubule-induced Pins/Galphai cortical polarity in Drosop... | ACCEPT | Summary: Pins forms an apical cortical crescent in neuroblasts. Reason: Repeatedly observed apical localization of Pins in neuroblasts. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:28712722 sequentially enriches Rok and Protein Kinase N (Pkn) on the apical neuroblast cortex |
| GO:0045179 apical cortex | IDA PMID:17726110 Galphai generates multiple Pins activation states to link co... | ACCEPT | Summary: Pins forms an apical cortical crescent in neuroblasts. Reason: Repeatedly observed apical localization of Pins in neuroblasts. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:28712722 sequentially enriches Rok and Protein Kinase N (Pkn) on the apical neuroblast cortex |
| GO:0045179 apical cortex | IDA PMID:28712722 Cell Polarity Regulates Biased Myosin Activity and Dynamics ... | ACCEPT | Summary: Pins forms an apical cortical crescent in neuroblasts. Reason: Repeatedly observed apical localization of Pins in neuroblasts. Supporting Evidence: PMID:16648843 Pins recruits Mud to the neuroblast apical cortex PMID:28712722 sequentially enriches Rok and Protein Kinase N (Pkn) on the apical neuroblast cortex |
| GO:0051294 establishment of spindle orientation | IMP PMID:16377571 Microtubule-induced Pins/Galphai cortical polarity in Drosop... | MODIFY | Summary: Pins/Galphai cortical domain is required for spindle orientation and asymmetry. Reason: Experimental support, but a less informative parent; MODIFY to establishment of mitotic spindle orientation, which pins already carries (IBA, IDA, IMP). Proposed replacements: establishment of mitotic spindle orientation Supporting Evidence: PMID:16377571 this cortical domain is functional for generating spindle asymmetry |
| GO:0055059 asymmetric neuroblast division | IMP PMID:12526793 Apical complex genes control mitotic spindle geometry and re... | ACCEPT | Summary: Pins is required for asymmetric neuroblast division. Reason: Core biological process; Pins/Galphai acts in parallel with Baz/aPKC to set spindle geometry and daughter size. Supporting Evidence: PMID:12526793 two parallel pathways (Bazooka/DaPKC and Pins/G alpha i) within the apical complex |
| GO:0055059 asymmetric neuroblast division | IMP PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation... | ACCEPT | Summary: Pins is required for asymmetric neuroblast division. Reason: Core biological process; Pins/Galphai acts in parallel with Baz/aPKC to set spindle geometry and daughter size. Supporting Evidence: PMID:12526793 two parallel pathways (Bazooka/DaPKC and Pins/G alpha i) within the apical complex |
| GO:1990499 raps-insc complex | IDA PMID:22171003 Inscuteable and NuMA proteins bind competitively to Leu-Gly-... | ACCEPT | Summary: Pins forms the Raps-Insc complex. Reason: Crystal structure of Pins TPR domain bound to Insc defines this complex. Supporting Evidence: PMID:22171003 The crystal structure of the Drosophila ortholog of LGN (known as Pins) in complex with Insc |
Loading supporting content…
Download this section (compressed HTML)Q: Should Pins-Insc and Pins-Mud complexes be modelled as mutually exclusive states, given that Insc and NuMA compete for the same LGN/Pins TPR surface?
Q: Pins is dispensable for spindle orientation in the wing imaginal disc epithelium (Bergstralh et al. 2016); which cortical factors localize Mud there, and how general is the Pins requirement outside neuroblasts and SOPs?
Loading supporting content…
Download this section (compressed HTML)partner of inscuteable (pins) encodes a GDP-dissociation inhibitor involved in asymmetric cell division and mitotic spindle orientation.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)