id: A0A9L0JLY3
gene_symbol: BICDL1
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: 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
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0034452
    label: dynactin binding
  predicted_term_type: GO_MF
  review:
    assessment: UNC
    confidence_score: 1
    summary: 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.
    supported_by:
    - reference_id: PMID:20360680
      supporting_text: 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
    - reference_id: PMID:29420470
      supporting_text: An approximate model for the BICDR1 coiled coil (residues 105-392) was generated by
        placing helices into density
    - reference_id: file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md
      supporting_text: the benchmark product is the only donkey model that lacks SEG_CORE
    - reference_id: file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS.md
      supporting_text: human residues 255-303
    - reference_id: file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS.md
      supporting_text: 'MOTIF (CC1 box): human [113, 114, 115, 116, 117] AARLG -> donkey [114, 115, 116,
        117, 118] AARLG.'
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0005813
    label: centrosome
  predicted_term_type: GO_CC
  review:
    assessment: UNC
    confidence_score: 1
    summary: 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.
    supported_by:
    - reference_id: PMID:20360680
      supporting_text: specifically localized around the γ-tubulin-labelled centrosome
    - reference_id: PMID:20360680
      supporting_text: Quantification showed that only ∼15% of the dynein/dynactin knockdown cells showed
        BICDR-1 around the centrosome compared with ∼74% in control cells
    - reference_id: PMID:29420470
      supporting_text: An approximate model for the BICDR1 coiled coil (residues 105-392) was generated by
        placing helices into density
    - reference_id: file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md
      supporting_text: the benchmark product is the only donkey model that lacks SEG_CORE
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0031267
    label: small GTPase binding
  predicted_term_type: GO_MF
  review:
    assessment: CNN
    confidence_score: 2
    summary: 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.
    supported_by:
    - reference_id: PMID:20360680
      supporting_text: 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
    - reference_id: PMID:20360680
      supporting_text: lysine 512 is required for binding to Rab6
    - reference_id: file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md
      supporting_text: It keeps the N-terminal CC1 box and the C-terminal region (the Rab6-binding region
        in mouse).
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0031175
    label: neuron projection development
  predicted_term_type: GO_BP
  review:
    assessment: NPI
    confidence_score: 0
    error_type: CURATION_MISTAKE
    summary: 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.
    supported_by:
    - reference_id: PMID:20360680
      supporting_text: 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
    - reference_id: PMID:20360680
      supporting_text: 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.
references:
- id: PMID:20360680
  title: Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates
    neuritogenesis.
  findings: []
- id: PMID:29420470
  title: Cryo-EM shows how dynactin recruits two dyneins for faster movement.
  findings: []
- id: file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS.md
  title: 'BICDL1: donkey-human sequence comparison'
  findings: []
- id: file:EQUAS/BICDL1/BICDL1-bioinformatics/RESULTS-rereview.md
  title: BICDL1 donkey gene-model comparison
  findings: []
