SPDL1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000132 establishment of mitotic spindle orientation	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for establishment of mitotic spindle orientation inferred by phylogenetic analysis. This is strongly supported by experimental evidence in human cells from PMID:19468067, which showed that hSpindly depletion induces striking spindle rotation that is rescued by co-depletion of dynein, demonstrating a direct role for kinetochore dynein in spindle orientation. Supporting Evidence: PMID:19468067 depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein
GO:0000922 spindle pole	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for spindle pole localization. Supported by direct experimental evidence (IDA) from PMID:19468067, which showed Spindly relocalizes to spindle poles before metaphase. Spindly is transported poleward by dynein along kinetochore fibers after microtubule attachment. Supporting Evidence: PMID:19468067 hSpindly decorated KTs in early prometaphase before it relocalized to the spindle poles before metaphase
GO:0000940 outer kinetochore	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for outer kinetochore localization. Strongly supported by IDA evidence from PMID:19468067 showing Spindly localizes to the outer kinetochore in early prometaphase. This is a core localization for Spindly, where it recruits dynein-dynactin to drive chromosome movements. Falcon deep research further localizes this to the kinetochore fibrous corona, the dynamic outer-kinetochore layer assembled in early mitosis. Supporting Evidence: PMID:19468067 localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B file:human/SPDL1/SPDL1-deep-research-falcon.md Spindly is specifically enriched at the kinetochore fibrous corona in early mitosis where it enables dynein–dynactin recruitment
GO:0007080 mitotic metaphase chromosome alignment	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for mitotic metaphase chromosome alignment. Strongly supported by IMP evidence from PMID:19468067, which showed that hSpindly depletion results in severe chromosome misalignment. This is a core biological process for Spindly. Supporting Evidence: PMID:19468067 hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment
GO:0034501 protein localization to kinetochore	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for protein localization to kinetochore. Supported by IMP evidence from PMID:19468067 and PMID:17576797. Spindly recruits dynein and dynactin to the kinetochore; depletion abolishes kinetochore dynein. This is a core function of Spindly. Falcon deep research details the recruitment mechanism: Spindly is targeted to kinetochores by the RZZ complex, with C-terminal farnesylation engaging the Rod beta-propeller as a farnesyl receptor. Supporting Evidence: PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly PMID:17576797 After the depletion of Spindly, dynein cannot target to kinetochores file:human/SPDL1/SPDL1-deep-research-falcon.md Spindly is recruited to kinetochores primarily through the RZZ complex (ROD–ZW10–ZWILCH). A key targeting mechanism is C-terminal farnesylation, with the Rod β-propeller acting as a farnesyl receptor in humans
GO:0043515 kinetochore binding	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for kinetochore binding. Supported by IDA evidence from PMID:19468067 showing direct localization to kinetochores. Spindly binds kinetochores via the RZZ complex, requiring C-terminal farnesylation for this interaction (PMID:25825516). Supporting Evidence: PMID:19468067 localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B
GO:0000922 spindle pole	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for spindle pole based on UniProt subcellular location mapping. Redundant with the IBA annotation for the same term, and both are supported by experimental IDA evidence from PMID:19468067.
GO:0000940 outer kinetochore	IEA GO_REF:0000104	ACCEPT	Summary: IEA annotation for outer kinetochore based on UniRule transfer. Redundant with the IBA annotation for the same term, both supported by IDA from PMID:19468067.
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: IEA annotation for nucleus based on UniProt subcellular location mapping. Supported by IDA evidence from PMID:19468067 showing Spindly localizes to the nucleus during interphase. This is a non-core localization representing the interphase state. Reason: Nuclear localization is the interphase state. The core localizations are the outer kinetochore and spindle pole during mitosis.
GO:0005813 centrosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: IEA annotation for centrosome based on UniProt subcellular location vocabulary mapping. UniProt lists centrosome as a subcellular location. This is plausible given that Spindly localizes to spindle poles (which contain centrosomes) during mitosis, though the primary experimental evidence places Spindly at the kinetochore and spindle pole rather than explicitly at the centrosome per se. This is a non-core secondary localization. Reason: Centrosome localization is implied by spindle pole localization but is not the primary or core localization for this protein.
GO:0007094 mitotic spindle assembly checkpoint signaling	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for SAC signaling based on InterPro domain mapping (IPR028593). The role of Spindly in SAC signaling is complex. In Drosophila, Spindly depletion prevents SAC silencing (PMID:17576797). In human cells, hSpindly depletion does NOT abolish removal of checkpoint proteins MAD2 and ZW10 from kinetochores (PMID:19468067), but Spindly mutants that cannot recruit dynein DO prevent checkpoint silencing (PMID:20439434). Thus Spindly is involved in SAC signaling primarily through its role in checkpoint silencing via dynein-mediated removal of checkpoint components. Falcon deep research updates this model with Ide et al. 2023: the checkpoint-silencing role of Spindly-recruited dynein is restricted primarily to disassembly of the fibrous corona, rather than wholesale removal of all checkpoint proteins from the outer kinetochore. Supporting Evidence: PMID:19468067 in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs PMID:17576797 Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore file:human/SPDL1/SPDL1-deep-research-falcon.md kinetochore dynein’s checkpoint-silencing role is restricted primarily to disassembly of the fibrous corona, rather than wholesale removal of checkpoint proteins from the entire outer kinetochore
GO:0034501 protein localization to kinetochore	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for protein localization to kinetochore via combined automated annotation. Redundant with IBA and IMP annotations for the same term. Well supported by experimental evidence.
GO:0043515 kinetochore binding	IEA GO_REF:0000104	ACCEPT	Summary: IEA annotation for kinetochore binding based on UniRule transfer. Redundant with IBA and IDA annotations for the same term. Well supported.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Protein binding annotation based on large-scale interactome study (Rolland et al. 2014). This is a generic, uninformative term. Spindly interacts with CA8, DNAAF4, PPP1R18, RTP5, TRAF4, USP15 in this dataset. These are high-throughput yeast two-hybrid results. The interactions with CA8 and DNAAF4 have no clear biological context for Spindly function. Reason: Protein binding is uninformative per GO curation guidelines. The specific biologically relevant interactions (with RZZ complex, dynein, dynactin, USP45) are captured by more specific terms. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	REMOVE	Summary: Protein binding annotation from large-scale interactome perturbation study (Sahni et al. 2015). Uninformative generic term from high-throughput data. Reason: Protein binding is uninformative per GO curation guidelines. Supporting Evidence: PMID:25910212 Widespread macromolecular interaction perturbations in human genetic disorders
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	REMOVE	Summary: Protein binding annotation from alternative splicing interactome study (Yang et al. 2016). Uninformative generic term from high-throughput data. Reason: Protein binding is uninformative per GO curation guidelines. Supporting Evidence: PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Protein binding annotation from BioPlex 3.0 dual proteome-scale network study (Huttlin et al. 2021). Uninformative generic term. Reason: Protein binding is uninformative per GO curation guidelines. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0005515 protein binding	IPI PMID:30258100 USP45 and Spindly are part of the same complex implicated in...	REMOVE	Summary: Protein binding annotation based on the USP45-Spindly interaction study (Conte et al. 2018). The IPI is with USP45 (Q70EL2). While the specific interaction is real and biologically relevant, protein binding is too generic. A more informative term would be enzyme binding (already captured elsewhere) or deubiquitinase binding. Reason: Protein binding is uninformative. The USP45 interaction is better captured by more specific MF terms. Supporting Evidence: PMID:30258100 we have identified Spindly as a new target of USP45
GO:0005515 protein binding	IPI PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	REMOVE	Summary: Protein binding annotation from Chan et al. 2009. The IPI partners are KNTC1/Rod (O43264) and KNTC2/ZW10 (P50748), components of the RZZ complex. These interactions are biologically central to Spindly function, as Spindly is recruited to kinetochores via the RZZ complex. However, protein binding is too generic; kinetochore binding (GO:0043515) and dynein complex binding (GO:0070840) are more informative. Reason: Protein binding is uninformative. The specific RZZ complex interaction is functionally captured by kinetochore binding and the dynein recruitment function. Supporting Evidence: PMID:19468067 RZZ members (ZW10 and Rod), but not dynein, could be coimmunoprecipitated with hSpindly
GO:0016477 cell migration	IMP PMID:30258100 USP45 and Spindly are part of the same complex implicated in...	KEEP AS NON CORE	Summary: IMP annotation for cell migration based on Conte et al. 2018, which showed that cells lacking Spindly migrate slower than wild-type cells. This was supported by an earlier report showing Spindly associates with the cell cortex and colocalizes with dynein/dynactin at the leading edge of migrating cells. This is a real but non-core function of Spindly; its primary evolved function is in mitotic kinetochore-dynein regulation. Reason: Cell migration is a documented secondary function of Spindly, but it is not the core evolved function. The core function is dynein recruitment to kinetochores during mitosis. Supporting Evidence: PMID:30258100 cells lacking Spindly migrate slower than wild type cells and that this effect is rescued by re-expression of wild-type Spindly
GO:0019899 enzyme binding	IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi...	KEEP AS NON CORE	Summary: Enzyme binding annotation from Armour et al. 2013 SIRT1 interactome study. The IPI partner is SIRT1 (Q96EB6). SPDL1 was identified as a SIRT1-interacting protein in a high-throughput screen. The biological significance of the SIRT1-Spindly interaction is unclear. This paper is primarily about USP22 and SAGA complex regulation; Spindly was a background hit. This is unlikely to represent a core function. Reason: The SIRT1 interaction is from a large-scale screen and its functional significance for Spindly is not established. However, enzyme binding is more informative than protein binding and the interaction data are real. Supporting Evidence: PMID:23382074 a comprehensive analysis of SIRT1 binding proteins yielding a high-confidence interaction map
GO:0005829 cytosol	TAS Reactome:R-HSA-141409	KEEP AS NON CORE	Summary: Cytosol annotation from Reactome pathway "Mad1 binds kinetochore." Spindly is included as a participant in SAC-related Reactome reactions. Multiple redundant TAS annotations for the same GO term from different Reactome reactions. The cytosol localization is correct as the interphase/soluble pool of Spindly, but this is non-core. Consolidating all Reactome cytosol entries into a single review. Reason: Cytosol is a valid but non-core localization for Spindly representing the soluble pool outside of mitosis.
GO:0005829 cytosol	TAS Reactome:R-HSA-141422	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-141431	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-141439	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-1638803	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-1638821	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-2467809	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-2467811	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-2468287	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-2484822	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-375302	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-5666129	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-5666160	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-5666169	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0005829 cytosol	TAS Reactome:R-HSA-9648114	KEEP AS NON CORE	Summary: Redundant cytosol TAS annotation from Reactome. Same assessment as above.
GO:0000132 establishment of mitotic spindle orientation	IMP PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	ACCEPT	Summary: IMP annotation for establishment of mitotic spindle orientation from Chan et al. 2009. hSpindly depletion induces striking spindle rotation that is rescued by co-depletion of dynein, demonstrating that kinetochore dynein (recruited by Spindly) is critical for spindle orientation. This is a core biological process for Spindly. Supporting Evidence: PMID:19468067 depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein
GO:0000922 spindle pole	IDA PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	ACCEPT	Summary: IDA annotation for spindle pole localization from Chan et al. 2009. Direct observation that Spindly relocalizes to spindle poles before metaphase via dynein-mediated poleward transport. Supporting Evidence: PMID:19468067 hSpindly decorated KTs in early prometaphase before it relocalized to the spindle poles before metaphase
GO:0000940 outer kinetochore	IDA PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	ACCEPT	Summary: IDA annotation for outer kinetochore localization from Chan et al. 2009. Direct observation by immunofluorescence showing Spindly localizes to the outer kinetochore in early prometaphase. This is the primary and core localization for Spindly during mitosis. Supporting Evidence: PMID:19468067 localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B
GO:0005515 protein binding	IPI PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	REMOVE	Summary: Protein binding annotation from Chan et al. 2009 based on interaction with KNTC1/Rod and ZW10. Uninformative term; the specific interactions are better captured by kinetochore binding. Reason: Protein binding is uninformative per GO curation guidelines. Supporting Evidence: PMID:19468067 RZZ members (ZW10 and Rod), but not dynein, could be coimmunoprecipitated with hSpindly
GO:0005634 nucleus	IDA PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	KEEP AS NON CORE	Summary: IDA annotation for nuclear localization from Chan et al. 2009. Spindly localizes to the nucleus in interphase. This is a non-core secondary localization reflecting the interphase distribution. Falcon deep research corroborates the cell-cycle localization dynamics: nuclear in interphase, then kinetochore in prometaphase. Reason: Nuclear localization is the interphase state; the core mitotic localizations are outer kinetochore and spindle pole. Supporting Evidence: PMID:19468067 Interphase localization of hSpindly was mainly nuclear file:human/SPDL1/SPDL1-deep-research-falcon.md Interphase: nuclear localization.
GO:0007080 mitotic metaphase chromosome alignment	IMP PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	ACCEPT	Summary: IMP annotation for mitotic metaphase chromosome alignment from Chan et al. 2009. hSpindly depletion causes severe chromosome misalignment with reduced inter-KT tension and unstable KT fibers. This is a core biological process for Spindly. Supporting Evidence: PMID:19468067 hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment
GO:0034501 protein localization to kinetochore	IMP PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	ACCEPT	Summary: IMP annotation for protein localization to kinetochore from Chan et al. 2009. Spindly is required for the recruitment of dynein and dynactin to kinetochores. Depletion abolishes kinetochore dynein. This is a core function of Spindly. Supporting Evidence: PMID:19468067 localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B PMID:17576797 After the depletion of Spindly, dynein cannot target to kinetochores
GO:0043515 kinetochore binding	IDA PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	ACCEPT	Summary: IDA annotation for kinetochore binding from Chan et al. 2009. Spindly directly binds kinetochores, as demonstrated by immunofluorescence microscopy. This binding is mediated via the RZZ complex and requires C-terminal farnesylation of Spindly (PMID:25825516). This is a core molecular function. Supporting Evidence: PMID:19468067 localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B
GO:0070840 dynein complex binding	IDA PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	NEW	Summary: NEW annotation. Spindly directly recruits the dynein-dynactin complex to kinetochores. Chan et al. 2009 showed that hSpindly depletion abolishes dynein localization to kinetochores. McKenney et al. 2014 demonstrated that Spindly functions as a cargo adaptor that physically links dynein to dynactin and activates processive motility. This is more informative than the generic protein binding annotations and represents a core molecular function. Falcon deep research specifies the binding logic of this activating adaptor: a CC1 box binding pocket engages a conserved amphipathic helix in dynein LIC, while the Spindly motif engages the dynactin pointed-end. Supporting Evidence: PMID:19468067 localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B PMID:25035494 Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes file:human/SPDL1/SPDL1-deep-research-bioreason-sft.md The dynein-adapter core enforces dynein targeting to microtubule minus ends and kinetochore receptors file:human/SPDL1/SPDL1-deep-research-falcon.md CC1 box: creates a binding pocket for a conserved amphipathic helix in dynein LIC (light intermediate chain).
GO:0007018 microtubule-based movement	IMP PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle...	NEW	Summary: NEW annotation. Spindly is required for dynein-dependent poleward chromosome movements during mitosis. hSpindly depletion results in reduced inter-KT tension and unstable KT fibers, consistent with impaired microtubule-based movement at kinetochores. Additionally, Spindly functions as a dynein-dynactin cargo adaptor that activates processive microtubule-based motility (PMID:25035494). Falcon deep research notes that Spindly-dependent dynein stripping (poleward transport of corona material) is triggered after end-coupled microtubule attachment. Supporting Evidence: PMID:19468067 hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment file:human/SPDL1/SPDL1-deep-research-falcon.md Spindly-dependent dynein stripping is triggered after end-coupled microtubule attachment, enabling removal of corona components (including Mad1–Mad2) and promoting kinetochore remodeling/compaction

Gene Description

Existing Annotations Review

Core Functions

Kinetochore-specific dynein adaptor that recruits cytoplasmic dynein-dynactin to the outer kinetochore during mitosis, enabling lateral kinetochore-microtubule interactions, poleward chromosome movements, chromosome congression, and spindle orientation control.

Dynein-dynactin cargo adaptor that activates processive dynein motility. Facilitates the interaction between dynein and dynactin and converts dynein from a non-processive to a highly processive motor.

Participates in spindle assembly checkpoint signaling through dynein-mediated removal of checkpoint proteins from kinetochores upon microtubule attachment. Spindly removal from attached kinetochores is the critical event for checkpoint silencing.

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