BICD2 (protein bicaudal D homolog 2) is a coiled-coil cargo adaptor and activator of cytoplasmic dynein-1. Its N-terminal coiled coil binds the dynein light intermediate chain and tail and runs along the dynactin Arp1 filament, stabilizing a dynein-dynactin-BICD2 complex that moves processively toward microtubule minus ends; its C-terminal coiled coil selects cargo and, in the cargo-free state, folds back to autoinhibit motor binding. In interphase BICD2 binds GTP-bound RAB6 on Golgi membranes and Golgi-derived/secretory vesicles, stabilizing RAB6 on the Golgi and supporting COPI-independent Golgi-to-ER retrograde transport. In G2, CDK1- and PLK1-dependent phosphorylation activates BICD2 and promotes its binding to CDK1-phosphorylated RANBP2 at the cytoplasmic face of nuclear pores, where it recruits dynein-dynactin (and regulates kinesin-1) to keep centrosomes tethered to the nucleus, drive centrosome separation and power apical interkinetic nuclear migration in radial glial progenitors. In postmitotic migrating neurons, BICD2 is recruited to the nuclear envelope by the LINC-complex protein nesprin-2 and couples dynein and kinesin-1 to the nucleus for nucleokinesis. Heterozygous BICD2 variants that alter dynein or cargo binding cause lower-extremity-predominant spinal muscular atrophy (SMALED2) and hereditary spastic paraplegia, and some variants affect cortical development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:16417406 Hem-1 complexes are essential for Rac activation, actin poly... | REMOVE | Summary: BICD2 co-purified in a proteomic analysis of Hem-1 (NCKAP1L) leading-edge complexes in neutrophil-like cells. Reason: GO:0005515 is uninformative, and co-purification with Hem-1 complexes in a proteomic survey does not define a BICD2 activity; no follow-up links BICD2 to Hem-1 function. |
| GO:0005515 protein binding | IPI PMID:20386726 Bicaudal D2, dynein, and kinesin-1 associate with nuclear po... | MODIFY | Summary: BICD2 C-terminus binds the nucleoporin RanBP2 directly, recruiting BICD2 to nuclear pores in G2. Reason: RanBP2 is a cargo of the BICD2 adaptor; the informative activity is BICD2 linking its RanBP2 cargo to dynein-dynactin (and kinesin-1), i.e. cytoskeletal adaptor activity. GO has no nucleoporin-binding MF term. Proposed replacements: cytoskeletal adaptor activity Supporting Evidence: PMID:20386726 the nuclear pore complex (NPC) component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle PMID:20386726 BICD2, in turn, recruits dynein-dynactin to NPCs and as such is needed to keep centrosomes closely tethered to the nucleus prior to mitotic entry |
| GO:0005515 protein binding | IPI PMID:23664119 Molecular defects in the motor adaptor BICD2 cause proximal ... | MODIFY | Summary: Co-immunoprecipitation of BICD2 with dynein intermediate chain (DYNC1I1, DNAI1) and RAB6A; SMA mutations alter dynein and RAB6A binding. Reason: The partners are dynein intermediate chains and the small GTPase RAB6A. Informative replacements are dynein complex binding and small GTPase binding, both core BICD2 interactions already annotated by other evidence. Proposed replacements: dynein complex binding small GTPase binding Supporting Evidence: PMID:23664119 p.Ser107Leu causes increased dynein binding and thus leads to accumulation of BICD2 at the microtubule-organizing complex and Golgi fragmentation PMID:23664119 The interaction between p.Glu744Gly altered BICD2 and RAB6A was impaired |
| GO:0005515 protein binding | IPI PMID:23664119 Molecular defects in the motor adaptor BICD2 cause proximal ... | MODIFY | Summary: Co-immunoprecipitation of BICD2 with dynein intermediate chain (DYNC1I1, DNAI1) and RAB6A; SMA mutations alter dynein and RAB6A binding. Reason: The partners are dynein intermediate chains and the small GTPase RAB6A. Informative replacements are dynein complex binding and small GTPase binding, both core BICD2 interactions already annotated by other evidence. Proposed replacements: dynein complex binding small GTPase binding Supporting Evidence: PMID:23664119 p.Ser107Leu causes increased dynein binding and thus leads to accumulation of BICD2 at the microtubule-organizing complex and Golgi fragmentation PMID:23664119 The interaction between p.Glu744Gly altered BICD2 and RAB6A was impaired |
| GO:0005515 protein binding | IPI PMID:23664119 Molecular defects in the motor adaptor BICD2 cause proximal ... | MODIFY | Summary: Co-immunoprecipitation of BICD2 with dynein intermediate chain (DYNC1I1, DNAI1) and RAB6A; SMA mutations alter dynein and RAB6A binding. Reason: The partners are dynein intermediate chains and the small GTPase RAB6A. Informative replacements are dynein complex binding and small GTPase binding, both core BICD2 interactions already annotated by other evidence. Proposed replacements: dynein complex binding small GTPase binding Supporting Evidence: PMID:23664119 p.Ser107Leu causes increased dynein binding and thus leads to accumulation of BICD2 at the microtubule-organizing complex and Golgi fragmentation PMID:23664119 The interaction between p.Glu744Gly altered BICD2 and RAB6A was impaired |
| GO:0005515 protein binding | IPI PMID:24482476 Exome sequencing links corticospinal motor neuron disease to... | REMOVE | Summary: Interaction of BICD2 with KIF1C reported in a hereditary spastic paraplegia exome/network study (abstract only in cache). Reason: GO:0005515 is uninformative. The interaction with kinesin-3 KIF1C derives from a network-level study, and the cached abstract does not describe it; no specific activity can be assigned from this evidence. |
| GO:0005635 nuclear envelope | IDA PMID:20386726 Bicaudal D2, dynein, and kinesin-1 associate with nuclear po... | ACCEPT | Summary: BICD2 at the nuclear envelope in G2 cells. Reason: BICD2 is recruited to the cytoplasmic face of the nuclear envelope in G2 by RanBP2 and, in migrating neurons, by nesprin-2, where it assembles dynein-dynactin and kinesin-1 on the nucleus. Supporting Evidence: PMID:20386726 the nuclear pore complex (NPC) component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle PMID:20386726 BICD2, in turn, recruits dynein-dynactin to NPCs and as such is needed to keep centrosomes closely tethered to the nucleus prior to mitotic entry |
| GO:0005635 nuclear envelope | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear envelope from UniProt subcellular location. Reason: BICD2 is recruited to the cytoplasmic face of the nuclear envelope in G2 by RanBP2 and, in migrating neurons, by nesprin-2, where it assembles dynein-dynactin and kinesin-1 on the nucleus. Supporting Evidence: PMID:20386726 the nuclear pore complex (NPC) component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle PMID:32619477 We report here that Nesprin-2 contributes to nuclear displacement during neuronal migration by recruiting microtubule motors to the NE, through the well-known adaptor BicD2. |
| GO:0005642 annulate lamellae | IDA PMID:20386726 Bicaudal D2, dynein, and kinesin-1 associate with nuclear po... | KEEP AS NON CORE | Summary: BICD2 on annulate lamellae (cytoplasmic NPC stacks) in a RanBP2-dependent manner in G2. Reason: Correct but minor location: annulate lamellae contain RanBP2-bearing pore complexes to which BICD2 is recruited; BICD2 also moves these cytoplasmic NPCs. Supporting Evidence: PMID:20386726 depletion of BICD2 inhibits both dynein and kinesin-1-dependent movements of the nucleus and cytoplasmic NPCs |
| GO:0005643 nuclear pore | IDA PMID:20386726 Bicaudal D2, dynein, and kinesin-1 associate with nuclear po... | KEEP AS NON CORE | Summary: BICD2 associates with nuclear pore complexes through RanBP2 in G2. Reason: BICD2 is transiently recruited to the cytoplasmic face of nuclear pores by RanBP2 in G2; it is a peripheral cargo adaptor rather than a structural pore-complex constituent. The location is correct but restricted to G2 and non-core; the nuclear envelope annotation captures the functional site. Supporting Evidence: PMID:20386726 the nuclear pore complex (NPC) component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle |
| GO:0005643 nuclear pore | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear pore from UniProt subcellular location. Reason: BICD2 is transiently recruited to the cytoplasmic face of nuclear pores by RanBP2 in G2; it is a peripheral cargo adaptor rather than a structural pore-complex constituent. The location is correct but restricted to G2 and non-core; the nuclear envelope annotation captures the functional site. Supporting Evidence: PMID:20386726 the nuclear pore complex (NPC) component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle |
| GO:0005737 cytoplasm | EXP PMID:23664116 Mutations in BICD2, which encodes a golgin and important mot... | ACCEPT | Summary: Cytoplasmic localization of BICD2 in SMA patient/transfected cells. Reason: BICD2 is a soluble cytoplasmic adaptor that associates with Golgi membranes, vesicles, microtubule plus ends and the nuclear envelope. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport |
| GO:0005737 cytoplasm | EXP PMID:23664120 Mutations in BICD2 cause dominant congenital spinal muscular... | ACCEPT | Summary: Cytoplasmic BICD2 in the dynein-dynactin adaptor study of DCSMA variants. Reason: BICD2 is a soluble cytoplasmic adaptor that associates with Golgi membranes, vesicles, microtubule plus ends and the nuclear envelope. Supporting Evidence: PMID:23664120 BICD2 encodes BICD2, a key adaptor protein that interacts with the dynein-dynactin motor complex |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm (UniProt SL). Reason: BICD2 is a soluble cytoplasmic adaptor that associates with Golgi membranes, vesicles, microtubule plus ends and the nuclear envelope. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport |
| GO:0005737 cytoplasm | IMP PMID:17139249 GSK-3beta-regulated interaction of BICD with dynein is invol... | ACCEPT | Summary: Cytoplasm, from the GSK-3beta/BICD centrosomal microtubule study. Reason: BICD2 is a soluble cytoplasmic adaptor that associates with Golgi membranes, vesicles, microtubule plus ends and the nuclear envelope. Supporting Evidence: PMID:17139249 Knockdown of GSK-3beta or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. |
| GO:0005794 Golgi apparatus | EXP PMID:23664116 Mutations in BICD2, which encodes a golgin and important mot... | ACCEPT | Summary: BICD2 localizes to the Golgi (golgin). Reason: In interphase, BICD2 is recruited to Golgi and Golgi-derived membranes by RAB6-GTP; it is described as a golgin, and SMA mutants cause Golgi fragmentation. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport PMID:23664116 BICD2 levels were reduced in affected individuals and trapped within the fragmented Golgi |
| GO:0005794 Golgi apparatus | EXP PMID:23664119 Molecular defects in the motor adaptor BICD2 cause proximal ... | ACCEPT | Summary: BICD2 at the Golgi; SMA mutants cause Golgi fragmentation and altered RAB6A colocalization. Reason: In interphase, BICD2 is recruited to Golgi and Golgi-derived membranes by RAB6-GTP; it is described as a golgin, and SMA mutants cause Golgi fragmentation. Supporting Evidence: PMID:23664119 p.Ser107Leu causes increased dynein binding and thus leads to accumulation of BICD2 at the microtubule-organizing complex and Golgi fragmentation |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi apparatus (IBA). Reason: In interphase, BICD2 is recruited to Golgi and Golgi-derived membranes by RAB6-GTP; it is described as a golgin, and SMA mutants cause Golgi fragmentation. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport PMID:25962623 BICD2 facilitates the binding of Rab6A to the Golgi by stabilizing its GTP-bound form |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: Golgi apparatus (HPA immunofluorescence). Reason: In interphase, BICD2 is recruited to Golgi and Golgi-derived membranes by RAB6-GTP; it is described as a golgin, and SMA mutants cause Golgi fragmentation. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | ACCEPT | Summary: Golgi apparatus (IEA). Reason: In interphase, BICD2 is recruited to Golgi and Golgi-derived membranes by RAB6-GTP; it is described as a golgin, and SMA mutants cause Golgi fragmentation. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport |
| GO:0005813 centrosome | IMP PMID:17139249 GSK-3beta-regulated interaction of BICD with dynein is invol... | KEEP AS NON CORE | Summary: Centrosome, from the BICD/GSK-3beta microtubule anchoring study. Reason: BICD-dynein delivers centrosomal proteins and hyperactive SMA mutant BICD2 accumulates at the MTOC, but BICD2 is not a stable centrosome component. The abstract discusses BICD generically (and BICD1), and the full text was not available; retained as a non-core location deferring to the curator. Supporting Evidence: PMID:17139249 Knockdown of GSK-3beta or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. PMID:23664119 p.Ser107Leu causes increased dynein binding and thus leads to accumulation of BICD2 at the microtubule-organizing complex and Golgi fragmentation |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosol (IBA). Reason: The soluble, autoinhibited pool of BICD2 is cytosolic. Supporting Evidence: PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoskeleton (UniProt SL). Reason: BICD2 associates with microtubule plus ends and microtubule-bound dynein-dynactin complexes. Supporting Evidence: PMID:22956769 tethering of BICD2-N to different membranes promotes their microtubule minus-end-directed motility |
| GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi-to-ER retrograde transport (IBA). Reason: BICD2 stabilizes GTP-bound RAB6A on Golgi membranes and, with dynein-dynactin, supports COPI-independent Golgi-to-ER retrograde transport. Supporting Evidence: PMID:25962623 BICD2 is involved in coat protein I (COPI)-independent Golgi-to-ER retrograde vesicular transport |
| GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: Golgi-to-ER retrograde transport (orthology). Reason: BICD2 stabilizes GTP-bound RAB6A on Golgi membranes and, with dynein-dynactin, supports COPI-independent Golgi-to-ER retrograde transport. Supporting Evidence: PMID:25962623 BICD2 is involved in coat protein I (COPI)-independent Golgi-to-ER retrograde vesicular transport |
| GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum | IMP PMID:25962623 Reconstitution of the targeting of Rab6A to the Golgi appara... | ACCEPT | Summary: BICD2 knockdown/perturbation impairs Golgi tubule fusion with the ER in BFA-treated cells. Reason: BICD2 stabilizes GTP-bound RAB6A on Golgi membranes and, with dynein-dynactin, supports COPI-independent Golgi-to-ER retrograde transport. Supporting Evidence: PMID:25962623 BICD2 is involved in coat protein I (COPI)-independent Golgi-to-ER retrograde vesicular transport PMID:25962623 BICD2 facilitates the binding of Rab6A to the Golgi by stabilizing its GTP-bound form |
| GO:0007018 microtubule-based movement | IBA GO_REF:0000033 | ACCEPT | Summary: Microtubule-based movement (IBA). Reason: BICD2 is an activating adaptor that converts dynein into a processive motor and tethers it to cargo, directly enabling microtubule-based cargo movement. Supporting Evidence: PMID:24986880 addition of dynactin together with the N-terminal region of the cargo adaptor BICD2 (BICD2N) gives rise to unidirectional dynein movement over remarkably long distances PMID:22956769 tethering of BICD2-N to different membranes promotes their microtubule minus-end-directed motility |
| GO:0008093 cytoskeletal adaptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Cytoskeletal adaptor activity (InterPro BICD). Reason: Core molecular function: BICD2 links cargos (RAB6-GTP vesicles, RanBP2, nesprin-2) to the microtubule motors dynein-dynactin and kinesin-1. Supporting Evidence: file:human/BICD2/BICD2-uniprot.txt Acts as an adapter protein linking the dynein motor complex PMID:20386726 BICD2, in turn, recruits dynein-dynactin to NPCs and as such is needed to keep centrosomes closely tethered to the nucleus prior to mitotic entry PMID:32619477 the motor proteins interact with Nesprin-2 through the dynein/kinesin "adaptor" BicD2, both in neurons and in non-mitotic fibroblasts file:human/BICD2/BICD2-deep-research-falcon.md It is a cargo-selective, coiled-coil |
| GO:0031267 small GTPase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Small GTPase binding (orthology). Reason: BICD2 C-terminal CC3 binds GTP-bound RAB6A (and RAB6B), stabilizing it on Golgi membranes; this is a well-established cargo interaction. Supporting Evidence: PMID:25962623 BICD2 facilitates the binding of Rab6A to the Golgi by stabilizing its GTP-bound form PMID:23664119 The interaction between p.Glu744Gly altered BICD2 and RAB6A was impaired |
| GO:0031267 small GTPase binding | ISS GO_REF:0000024 | ACCEPT | Summary: Small GTPase binding (sequence similarity). Reason: BICD2 C-terminal CC3 binds GTP-bound RAB6A (and RAB6B), stabilizing it on Golgi membranes; this is a well-established cargo interaction. Supporting Evidence: PMID:25962623 BICD2 facilitates the binding of Rab6A to the Golgi by stabilizing its GTP-bound form PMID:23664119 The interaction between p.Glu744Gly altered BICD2 and RAB6A was impaired |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: Cytoplasmic vesicle (orthology). Reason: BICD2 associates with RAB6-positive Golgi-derived and secretory vesicles as their dynein/kinesin adaptor. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport |
| GO:0031410 cytoplasmic vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic vesicle (sequence similarity). Reason: BICD2 associates with RAB6-positive Golgi-derived and secretory vesicles as their dynein/kinesin adaptor. Supporting Evidence: PMID:23664116 BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport |
| GO:0034067 protein localization to Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Protein localization to Golgi apparatus (IBA). Reason: BICD2 stabilizes GTP-bound RAB6A on Golgi membranes, promoting RAB6A Golgi targeting. Supporting Evidence: PMID:25962623 BICD2 facilitates the binding of Rab6A to the Golgi by stabilizing its GTP-bound form |
| GO:0034067 protein localization to Golgi apparatus | IEA GO_REF:0000107 | ACCEPT | Summary: Protein localization to Golgi apparatus (orthology). Reason: BICD2 stabilizes GTP-bound RAB6A on Golgi membranes, promoting RAB6A Golgi targeting. Supporting Evidence: PMID:25962623 BICD2 facilitates the binding of Rab6A to the Golgi by stabilizing its GTP-bound form |
| GO:0034067 protein localization to Golgi apparatus | IMP PMID:25962623 Reconstitution of the targeting of Rab6A to the Golgi appara... | ACCEPT | Summary: BICD2 is the cytosolic factor for RAB6A Golgi targeting in semi-intact cells. Reason: BICD2 stabilizes GTP-bound RAB6A on Golgi membranes, promoting RAB6A Golgi targeting. Supporting Evidence: PMID:25962623 BICD2 facilitates the binding of Rab6A to the Golgi by stabilizing its GTP-bound form |
| GO:0034452 dynactin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Dynactin binding (IBA). Reason: The BICD2 N-terminal coiled coil runs along the dynactin Arp1 filament and stabilizes the dynein-dynactin-BICD2 complex. Supporting Evidence: PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. PMID:22956769 BICD2 N-terminus (BICD2-N) strongly promotes stable interaction between dynein and dynactin both in vitro and in vivo |
| GO:0034452 dynactin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Dynactin binding (orthology). Reason: The BICD2 N-terminal coiled coil runs along the dynactin Arp1 filament and stabilizes the dynein-dynactin-BICD2 complex. Supporting Evidence: PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. |
| GO:0034452 dynactin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Dynactin binding (sequence similarity). Reason: The BICD2 N-terminal coiled coil runs along the dynactin Arp1 filament and stabilizes the dynein-dynactin-BICD2 complex. Supporting Evidence: PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. |
| GO:0051642 centrosome localization | IMP PMID:20386726 Bicaudal D2, dynein, and kinesin-1 associate with nuclear po... | ACCEPT | Summary: BICD2 depletion loosens centrosome-nucleus tethering in G2. Reason: By recruiting dynein-dynactin to nuclear pores, BICD2 keeps centrosomes tethered to the nucleus before mitotic entry; phosphorylation-regulated BICD2 is also required for centrosome separation. Supporting Evidence: PMID:20386726 BICD2, in turn, recruits dynein-dynactin to NPCs and as such is needed to keep centrosomes closely tethered to the nucleus prior to mitotic entry PMID:37105961 BICD2 phosphorylation is central for dynein recruitment to the nuclear envelope, centrosome tethering to the nucleus and centrosome separation in the G2 and M phases of the cell cycle |
| GO:0051959 dynein light intermediate chain binding | IBA GO_REF:0000033 | ACCEPT | Summary: Dynein light intermediate chain binding (IBA). Reason: BICD2's N-terminal CC1 box contacts the dynein light intermediate chain helix, a conserved adaptor-LIC interface needed for activation. Supporting Evidence: file:human/BICD2/BICD2-deep-research-falcon.md a conserved transient helix in LIC1/LIC2 binds the N-terminal region of BICD2 and other activating adaptors |
| GO:0051959 dynein light intermediate chain binding | IEA GO_REF:0000107 | ACCEPT | Summary: Dynein light intermediate chain binding (orthology). Reason: BICD2's N-terminal CC1 box contacts the dynein light intermediate chain helix, a conserved adaptor-LIC interface needed for activation. Supporting Evidence: file:human/BICD2/BICD2-deep-research-falcon.md a conserved transient helix in LIC1/LIC2 binds the N-terminal region of BICD2 and other activating adaptors |
| GO:0070507 regulation of microtubule cytoskeleton organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Regulation of microtubule cytoskeleton organization (IBA). Reason: BICD/dynein and GSK-3beta are needed for focused centrosomal microtubule arrays, likely by delivering centrosomal proteins; this is an indirect consequence of dynein transport. The GSK-3beta paper emphasizes BICD1, and paralog attribution cannot be checked in the abstract, so retained as non-core. Supporting Evidence: PMID:17139249 Knockdown of GSK-3beta or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. |
| GO:0070507 regulation of microtubule cytoskeleton organization | IGI PMID:17139249 GSK-3beta-regulated interaction of BICD with dynein is invol... | KEEP AS NON CORE | Summary: BICD and GSK-3beta knockdown reduce centrosomally focused microtubules. Reason: BICD/dynein and GSK-3beta are needed for focused centrosomal microtubule arrays, likely by delivering centrosomal proteins; this is an indirect consequence of dynein transport. The GSK-3beta paper emphasizes BICD1, and paralog attribution cannot be checked in the abstract, so retained as non-core. Supporting Evidence: PMID:17139249 Knockdown of GSK-3beta or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. |
| GO:0070840 dynein complex binding | IBA GO_REF:0000033 | ACCEPT | Summary: Dynein complex binding (IBA). Reason: BICD2 binds cytoplasmic dynein-1 (via LIC and the heavy chain tail) in the dynein-dynactin-BICD2 complex; SMA mutations increase dynein binding. Supporting Evidence: PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. PMID:23664119 p.Ser107Leu causes increased dynein binding and thus leads to accumulation of BICD2 at the microtubule-organizing complex and Golgi fragmentation |
| GO:0070840 dynein complex binding | IEA GO_REF:0000120 | ACCEPT | Summary: Dynein complex binding (IEA). Reason: BICD2 binds cytoplasmic dynein-1 (via LIC and the heavy chain tail) in the dynein-dynactin-BICD2 complex; SMA mutations increase dynein binding. Supporting Evidence: PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. |
| GO:0070840 dynein complex binding | ISS GO_REF:0000024 | ACCEPT | Summary: Dynein complex binding (sequence similarity). Reason: BICD2 binds cytoplasmic dynein-1 (via LIC and the heavy chain tail) in the dynein-dynactin-BICD2 complex; SMA mutations increase dynein binding. Supporting Evidence: PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. PMID:23664120 BICD2 encodes BICD2, a key adaptor protein that interacts with the dynein-dynactin motor complex |
| GO:0072385 minus-end-directed organelle transport along microtubule | IEA GO_REF:0000107 | ACCEPT | Summary: Minus-end-directed organelle transport along microtubule (orthology). Reason: Membrane tethering of BICD2 drives minus-end-directed organelle motility via dynein-dynactin. Supporting Evidence: PMID:22956769 tethering of BICD2-N to different membranes promotes their microtubule minus-end-directed motility |
| GO:0072385 minus-end-directed organelle transport along microtubule | ISS GO_REF:0000024 | ACCEPT | Summary: Minus-end-directed organelle transport along microtubule (similarity). Reason: Membrane tethering of BICD2 drives minus-end-directed organelle motility via dynein-dynactin. Supporting Evidence: PMID:22956769 tethering of BICD2-N to different membranes promotes their microtubule minus-end-directed motility |
| GO:0072393 microtubule anchoring at microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Microtubule anchoring at MTOC (IBA). Reason: Derived from BICD/GSK-3beta evidence that BICD-dynein is needed for anchoring microtubules at the centrosome; indirect, likely via transport of centrosomal anchoring proteins, and partly attributed to BICD1. Non-core. Supporting Evidence: PMID:17139249 Microtubule regrowth assays showed that GSK-3beta and BICD are required for the anchoring of microtubules to the centrosome. |
| GO:0072393 microtubule anchoring at microtubule organizing center | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Microtubule anchoring at MTOC (orthology). Reason: Derived from BICD/GSK-3beta evidence that BICD-dynein is needed for anchoring microtubules at the centrosome; indirect, likely via transport of centrosomal anchoring proteins, and partly attributed to BICD1. Non-core. Supporting Evidence: PMID:17139249 Microtubule regrowth assays showed that GSK-3beta and BICD are required for the anchoring of microtubules to the centrosome. |
| GO:0072393 microtubule anchoring at microtubule organizing center | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Microtubule anchoring at MTOC (similarity). Reason: Derived from BICD/GSK-3beta evidence that BICD-dynein is needed for anchoring microtubules at the centrosome; indirect, likely via transport of centrosomal anchoring proteins, and partly attributed to BICD1. Non-core. Supporting Evidence: PMID:17139249 Microtubule regrowth assays showed that GSK-3beta and BICD are required for the anchoring of microtubules to the centrosome. |
| GO:0007097 nuclear migration | ISS PMID:32619477 Nesprin-2 Recruitment of BicD2 to the Nuclear Envelope Contr... | NEW | Summary: BICD2 couples dynein-dynactin and kinesin-1 to the nucleus (via nesprin-2 in neurons, RanBP2 in G2 progenitors) and is required for nuclear movement. Reason: BICD2 does work in nuclear migration: it is the adaptor that physically links the nuclear-envelope cargo (nesprin-2 or RanBP2) to dynein-dynactin and kinesin-1 and activates dynein. Disrupting the nesprin-2/BicD2 interaction blocks nuclear movement in migrating rat cortical neurons, BicD2 RNAi arrests apical interkinetic nuclear migration in radial glial progenitors, and BICD2 depletion disrupts dynein- and kinesin-dependent nuclear movements in human G2 cells. Comparator check: other components in the same adaptor/motor role (HOOK3 for interkinetic nuclear migration; DYNC1H1, PAFAH1B1, SYNE2 for nuclear migration) carry this branch in human GOA, so the absence for BICD2 is a gap rather than a convention. The rat evidence is from the orthologue. Supporting Evidence: PMID:32619477 Although disruption of the Nesprin-2/BicD2 interaction severely inhibited nuclear movement, centrosome advance proceeded unimpeded PMID:32619477 We report here that Nesprin-2 contributes to nuclear displacement during neuronal migration by recruiting microtubule motors to the NE, through the well-known adaptor BicD2. PMID:24034252 BicD2 RNAi caused specific inhibition of apical, but not basal nuclear migration with nuclei arrested at least 30 ΞΌm from the ventricular surface throughout the recording period PMID:24034252 two distinct G2-specific mechanisms for dynein nuclear pore recruitment are essential for apical nuclear migration PMID:20386726 depletion of BICD2 inhibits both dynein and kinesin-1-dependent movements of the nucleus and cytoplasmic NPCs |
| GO:0140660 cytoskeletal motor activator activity | IDA PMID:24986880 In vitro reconstitution of a highly processive recombinant h... | NEW | Summary: BICD2 N-terminus, with dynactin, converts recombinant human dynein from a non-processive to a highly processive minus-end-directed motor. Reason: Reconstitution with purified recombinant human dynein shows that BICD2N plus dynactin stimulate processivity of individual dynein complexes; BICD2 binds and increases the activity of the motor, which is the definition of cytoskeletal motor activator activity. This captures BICD2's activating-adaptor role, which dynein/dynactin binding terms do not. Supporting Evidence: PMID:24986880 addition of dynactin together with the N-terminal region of the cargo adaptor BICD2 (BICD2N) gives rise to unidirectional dynein movement over remarkably long distances PMID:24986880 BICD2N and dynactin stimulate processivity by regulating individual dynein complexes file:human/BICD2/BICD2-uniprot.txt to various cargos and converts dynein from a non-processive to a highly PMID:25814576 The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components. |
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Download this section (compressed HTML)Q: Should activating dynein adaptors (BICD2, HOOK3, BICDR1, SPDL1, NINL) be consistently annotated to GO:0140660 cytoskeletal motor activator activity in addition to dynein/dynactin binding?
Suggested experts: GO molecular function editors, dynein motor biophysicists
Q: Is BICD2 required for nucleokinesis in human cortical neurons, and do cargo-selective SMA/brain-malformation variants (e.g. E770G, K785M) separate the RANBP2 and nesprin-2 routes in human cells?
Suggested experts: neuronal migration biologists, BICD2 clinical geneticists
Experiment: Express cargo-selective BICD2 variants (RANBP2-binding-deficient vs nesprin-2-binding-deficient) in human iPSC-derived cortical organoids and image progenitor INM and neuronal nucleokinesis to test route specificity in human tissue.
Type: variant rescue with live imaging in organoids
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