BICDL1

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

GO Term	Evidence	Action	Reason
GO:0047496 vesicle transport along microtubule	IEA GO_REF:0000118	ACCEPT	Summary: BICDL1 recruits dynein-dynactin and KIF1C to Rab6-positive secretory vesicles. In this way it controls their microtubule-based traffic and their accumulation around the centrosome. Reason: This is a TreeGrafter transfer within PANTHER subfamily PTHR32123:SF12 (BICD family-like cargo adapter 1). That subfamily also contains the experimentally characterised mouse Bicdl1/BICDR-1 (A0JNT9) and human BICDL1. The PAINT IBD for this term sits on the deuterostome node PTN001281025, so donkey falls inside the clade that inherited the function. Mouse BICDR-1 drives dynein-dependent traffic of Rab6/NPY secretory vesicles, which knockdown and overexpression experiments show. The benchmark donkey product keeps the CC1 box and the C-terminal Rab6-binding region, although it is an alternative splice form. The term describes the core process. Supporting Evidence: PMID:20360680 Here, we show that BICDR-1 is a Rab6 effector, recruits dynein/dynactin and Kif1C to Rab6/NPY-positive secretory vesicles and controls the trafficking and distribution of these carriers. file:EQUAS/BICDL1/BICDL1-bioinformatics/human_Q6ZP65-uniprot.txt Regulates the secretory vesicle transport by controlling the accumulation of Rab6-containing secretory vesicles in the pericentrosomal region file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md It keeps the N-terminal CC1 box and the C-terminal region (the Rab6-binding region in mouse).
GO:0055107 Golgi to secretory granule transport	IEA GO_REF:0000118	KEEP AS NON CORE	Summary: BICDL1 regulates the post-Golgi movement of Rab6/NPY-positive secretory carriers. Mostly it holds them near the centrosome instead of delivering them to the periphery. Reason: A PAINT curator placed this term on node PTN001281025, using mouse Bicdl1 (MGI:1922915) as the seed, and donkey inherits it through SF12. The carriers that BICDR-1 controls contain Rab6 and NPY-GFP, and NPY is a dense-core secretory cargo, so the term's cargo is a reasonable fit. However, BICDR-1 mainly retains these vesicles in the pericentrosomal region and limits their anterograde secretory transport. Its role in Golgi-to-granule delivery is therefore regulatory and depends on context. The more general vesicle-transport-along-microtubule term is the core process. This term is kept as true but non-core, in deference to the IBD. Supporting Evidence: PMID:20360680 Hela cells co-transfected with mCherry-BICDR-1 and NPY-GFP and stained for endogenous Rab6A showed that most of the centrosomal BICDR-1-positive vesicles contain NPY-GFP PMID:20360680 At early developmental stages, pericentrosomal BICDR-1 restricts secretory transport and inhibits neuritogenesis, whereas later during neuronal development the reduction in BICDR-1 expression permits anterograde transport required for neurite outgrowth.
GO:0140660 cytoskeletal motor activator activity	ISS PMID:29420470 Cryo-EM shows how dynactin recruits two dyneins for faster m...	NEW	Summary: As an activating adaptor, BICDL1 turns dynein-dynactin into a processive motor. Because it preferentially recruits two dyneins, the motor is faster and generates more force. Reason: The donkey GOA record has no molecular function. In in vitro reconstitution, BICDR1-dynein-dynactin complexes move processively, and about 94% of them contain two dyneins. This is the defining activity of the BICDR subfamily, and cytoskeletal motor activator activity is the term that fits it. Transfer is justified because donkey is in the same PANTHER subfamily (SF12) as mouse Bicdl1 and keeps the CC1 box, the dynein light-intermediate-chain binding motif that this activity needs. The central coiled-coil exon missing from this splice form may change the length of the adaptor. It does not remove the dynein-binding N-terminus. Supporting Evidence: PMID:29420470 We conclude the majority of motile complexes containing BICD2 have one dynein, whereas both BICDR1 and HOOK3 preferentially recruit two. PMID:29420470 This arrangement results in a dynein/dynactin complex that moves faster and can produce larger forces. file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS.md MOTIF (CC1 box): human [113, 114, 115, 116, 117] AARLG -> donkey [114, 115, 116, 117, 118] AARLG.

ProtNLM2 External predictions

View prediction review YAML · BICDL1-protnlm-predictions-review.yaml · Review status: COMPLETE

Assessment of 4 ProtNLM2 GO predictions for donkey BICDL1 (A0A9L0JLY3), scored for this exact product. A0A9L0JLY3 is a non-canonical splice form of the donkey BICDL1 gene that keeps the N-terminal CC1 box and the C-terminal Rab6-binding region but lacks a 49-residue central coiled-coil segment (human Q6ZP65 residues 255-303) present in human, mouse and every other donkey product, and includes the alternative exon of human isoform 2 (95.99% identity to human Q6ZP65 over 524 paired residues). The canonical product of the same gene (A0A9L0K8K5) already carries all four predicted terms in GOA as Ensembl Compara transfers from mouse Bicdl1, so none of the predictions is novel at the gene level. Small GTPase binding depends on the retained C-terminal region and is assessed CNN. Dynactin binding and centrosome localization depend on the coiled coil that lies along dynactin in the BICDR1-dynein-dynactin cryo-EM structure; because the missing segment falls within that stretch and no experiment tests the shortened adaptor, both are assessed UNC. Neuron projection development is assessed NPI, because the mouse evidence behind it is an overexpression phenotype in which BICDR-1 inhibits neurite outgrowth indirectly by retaining Rab6 secretory vesicles near the centrosome; the positive process term misstates that relationship. A PubMed search (BICDL1, BICDR1, BICDR-1, CCDC64) found no further experimental work bearing on these terms beyond PMID:20360680 and the dynein-dynactin structural studies. ProtNLM2 emitted no non-GO function-text or subcellular-location output for this accession in the frozen snapshot.

Source documents: genes/EQUAS/BICDL1/BICDL1-uniprot.txt · genes/EQUAS/BICDL1/BICDL1-goa.tsv · genes/EQUAS/BICDL1/BICDL1-ai-review.yaml · genes/EQUAS/BICDL1__A0A9L0K8K5/BICDL1__A0A9L0K8K5-goa.tsv · genes/EQUAS/BICDL1__A0A9L0K8K5/BICDL1__A0A9L0K8K5-ai-review.yaml · genes/mouse/Bicdl1/Bicdl1-ai-review.yaml · genes/EQUAS/BICDL1/BICDL1-bioinformatics/human_Q6ZP65-uniprot.txt · genes/EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS.md · genes/EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md · projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0034452 dynactin binding GO_MF

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14

Review rationale: Dynactin binding is a true activity of the BICDL1 gene. Mouse BICDR-1 co-immunoprecipitates the major dynein and dynactin subunits, and in the cryo-EM structure of the dynein-dynactin-BICDR1 complex the BICDR1 coiled coil, modelled over mouse residues 105-392, lies along the dynactin filament. The term is already carried in GOA by the canonical product of the same donkey gene (A0A9L0K8K5), so it would not be novel. This accession, however, is a non-canonical splice form that lacks a 49-residue central coiled-coil segment (human Q6ZP65 residues 255-303, SEG_CORE) present in human, mouse and every other donkey product. That segment falls inside the coiled-coil stretch that contacts dynactin in the structure. The accession keeps the N-terminal CC1 box, but no experiment shows whether an adaptor with this shortened coiled coil still spans and binds dynactin. Whether this product retains the dynactin-binding interface is therefore unresolved.

Supporting Evidence:

PMID:20360680: "Co-immunoprecipitation experiments from Hela cells transfected with GFP-BICDR-1 showed that BICDR-1 precipitates the major dynein/dynactin subunits, whereas no binding is seen with control GFP"
PMID:29420470: "An approximate model for the BICDR1 coiled coil (residues 105-392) was generated by placing helices into density"
file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md: "the benchmark product is the only donkey model that lacks SEG_CORE"
file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS.md: "human residues 255-303"
file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS.md: "MOTIF (CC1 box): human [113, 114, 115, 116, 117] AARLG -> donkey [114, 115, 116, 117, 118] AARLG."

GO:0005813 centrosome GO_CC

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14

Review rationale: Endogenous mouse BICDR-1 localizes around the gamma-tubulin-labelled centrosome, where it holds Rab6 secretory vesicles, and this localization depends on dynein and dynactin, since knockdown of either largely abolishes it. The term is already carried in GOA by the canonical donkey product A0A9L0K8K5, so it would not be novel. This accession is a non-canonical splice form that lacks the central coiled-coil segment (human Q6ZP65 residues 255-303, SEG_CORE) lying within the coiled coil that contacts dynactin. Because pericentrosomal targeting requires dynein-dynactin recruitment, and it is unresolved whether the shortened coiled coil of this product still engages dynactin, it cannot be determined whether this product localizes to the centrosome.

Supporting Evidence:

PMID:20360680: "specifically localized around the γ-tubulin-labelled centrosome"
PMID:20360680: "Quantification showed that only ∼15% of the dynein/dynactin knockdown cells showed BICDR-1 around the centrosome compared with ∼74% in control cells"
PMID:29420470: "An approximate model for the BICDR1 coiled coil (residues 105-392) was generated by placing helices into density"
file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md: "the benchmark product is the only donkey model that lacks SEG_CORE"

GO:0031267 small GTPase binding GO_MF

CNN — Correct but not novel Review score: 2/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14

Review rationale: Mouse BICDR-1 is a Rab6 effector; full-length protein and its C-terminal region bind GTP-locked Rab6A but not GDP-locked Rab6A, and Lys512 is required for this binding. The donkey product is in the same PANTHER subfamily and keeps the C-terminal BICDL1/2-like region, so the transfer is a justified orthology inference. Small GTPase binding is the most specific applicable GO term used for this activity in the reviews. The term is already carried in GOA by the canonical donkey product A0A9L0K8K5 and is a core function of the target's gene review, so the prediction is correct but not novel.

Supporting Evidence:

PMID:20360680: "Moreover, both full-length BICDR-1 and a C-terminal region of BICDR-1, amino acids 382–577, interact with constitutively active GTPase-deficient Rab6A-Q72R and not with GDP-locked inactive Rab6A-T27N in the yeast two-hybrid assay"
PMID:20360680: "lysine 512 is required for binding to Rab6"
file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md: "It keeps the N-terminal CC1 box and the C-terminal region (the Rab6-binding region in mouse)."

GO:0031175 neuron projection development GO_BP

NPI — Nonparalog incorrect Review score: 0/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14

CURATION MISTAKE

Review rationale: The only experimental evidence linking BICDR-1 to neurites is an overexpression phenotype in cultured hippocampal neurons, where sustained BICDR-1 expression reduces neurite outgrowth by retaining Rab6 secretory vesicles in the pericentrosomal region; the authors conclude that BICDR-1 inhibits neuritogenesis early in differentiation. BICDL1 therefore does not perform neurite development; at most it negatively and indirectly regulates it through its vesicle-transport function. The positive process term matches the mouse IMP annotation that the mouse gene review modifies to negative regulation of neuron projection development, and the canonical donkey product's review marks the same term over-annotated on these grounds. The prediction reproduces that mis-signed source annotation rather than the supported role.

Supporting Evidence:

PMID:20360680: "At 2, 3 and 4 days after transfection, BICDR-1-transfected neurons showed a marked reduction in neurite outgrowth compared with control cells transfected with an empty vector and β-galactosidase"
PMID:20360680: "At early developmental stages, pericentrosomal BICDR-1 restricts secretory transport and inhibits neuritogenesis, whereas later during neuronal development the reduction in BICDR-1 expression permits anterograde transport required for neurite outgrowth."

Gene Description

Existing Annotations Review

Core Functions

Activating adaptor that links cytoplasmic dynein-dynactin to Rab6-positive secretory vesicles. It activates processive minus-end motility by recruiting two dyneins, and it concentrates the vesicles around the centrosome.

Rab6 effector that binds GTP-bound Rab6 through its C-terminal region and so attaches the dynein adaptor to its secretory vesicle cargo.

References

Suggested Questions for Experts

Suggested Experiments

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Cyberian

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Notes

Bioinformatics Results

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