id: ARBA00088058
description: Rule predicts GO:0051010 (microtubule plus-end binding) for proteins
  containing CAP-Gly domains (CLIP proteins), EB/RP family proteins, CLASP proteins,
  or CKAP5, in five condition sets with taxon-specific targeting across Glires, Primates,
  Fungi, and broader Eukaryota.
status: COMPLETE
rule_type: ARBA
action: ACCEPT
confidence: 0.85
action_rationale: The rule correctly identifies well-characterized microtubule plus-end
  binding protein families (CAP-Gly domain proteins, EB/RP family, CLASP proteins,
  XMAP215/ch-TOG). Literature evidence strongly supports plus-end binding for all
  targeted families. After removing redundant FunFams, this represents a biologically
  sound annotation rule with strong experimental support.
parsimony:
  assessment: REDUNDANT
  notes: 'Rule contains significant redundancy issues:

    1. Condition Set 1 has two completely redundant FunFams (2.30.30.190:FF:000001
    and 2.30.30.190:FF:000002) covering identical proteins in Glires. One should be
    removed.

    2. Condition Set 3 has two redundant FunFams (1.25.10.10:FF:000001 and 1.25.10.10:FF:000005),
    both for CLIP-associating protein 1 isoform 2 in Primates. One should be removed.

    3. Condition Set 2 contains redundant FunFams: 1.20.5.1430:FF:000001 (microtubule-associated
    protein RP/EB family member 1) is entirely contained within 1.10.418.10:FF:000007
    (RP/EB family member 2). The subset FunFam adds no additional coverage and should
    be removed.

    These redundancies violate parsimony principles and create unnecessary rule complexity
    without improving annotation coverage.

    '
  supported_by:
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-perplexity.md
    supporting_text: Several condition sets in ARBA00088058 show considerable conceptual
      overlap. Condition Sets 1 and 3 both target CAP-Gly-containing linker proteins
      (CLIP family), differing only in taxonomic scope. Condition Set 2 targets EB
      proteins broadly across eukaryotes, while Condition Set 4 targets EB proteins
      specifically in fungi.
literature_support:
  assessment: STRONG
  notes: The GO term GO:0051010 (microtubule plus-end binding) is strongly supported
    by extensive experimental evidence for all targeted protein families (CAP-Gly
    domain proteins, RP/EB family proteins, CLIP-associating proteins, XMAP215/ch-TOG
    family). These are canonical microtubule plus-end tracking proteins (+TIPs) with
    well-characterized biochemical mechanisms for plus-end localization. While this
    specific GO term is notably absent from InterPro2GO mappings (suggesting a more
    granular annotation than typically inferred from domain presence alone), the biological
    function is robustly supported by multiple lines of evidence including live-cell
    imaging, in vitro reconstitution, structural biology, and genetic studies. The
    domain-based prediction is reliable because these protein families have evolved
    specialized structural features (CAP-Gly domains, EB CH domains, TOG arrays) specifically
    for plus-end recognition, distinguishing them from general microtubule-binding
    proteins.
  supported_by:
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-perplexity.md
    supporting_text: The literature supporting the proposed annotation rule is extensive
      and compelling. The founding observations that CLIP-170 and EB proteins track
      growing microtubule plus ends have been reproduced in numerous laboratories
      using multiple experimental approaches. The biochemical evidence for CAP-Gly
      domain binding to tubulin is robust and has been validated by structural biology.
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-falcon.md
    supporting_text: 'EB/RP family (+TIP autonomous plus-end binding at GTP cap):
      Mechanism and in vitro/in vivo behavior: EBs recognize the GTP-like cap, with
      higher affinity to specific nucleotide states; depletion alters catastrophe
      frequency and growth persistence; paralog differences in tip affinity. Evidence
      includes TIRF, tubulin mutants, and cellular perturbations.'
condition_overlap:
  assessment: SIGNIFICANT
  notes: Condition Set 4 (EB proteins in Fungi) is entirely subsumed by Condition
    Set 2 (EB proteins in all Eukaryota). Additionally, Condition Sets 1 and 3 both
    target CAP-Gly proteins with different taxonomic scopes.
  supported_by:
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-perplexity.md
    supporting_text: The five condition sets in ARBA00088058 show considerable conceptual
      overlap. Condition Sets 1 and 3 both target CAP-Gly-containing linker proteins
      (CLIP family), differing only in taxonomic scope. Condition Set 2 targets EB
      proteins broadly across eukaryotes, while Condition Set 4 targets EB proteins
      specifically in fungi. These overlapping conditions suggest the rule could be
      simplified.
go_specificity:
  assessment: APPROPRIATE
  notes: The GO term microtubule plus-end binding is appropriate for these protein
    families
  supported_by:
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-perplexity.md
    supporting_text: For CAP-Gly-containing proteins, the GO term GO:0051010 is highly
      appropriate. CAP-Gly domains have evolved specifically to recognize and bind
      C-terminal tubulin sequences, with binding affinities and specificities consistent
      with functional microtubule plus-end recognition. For EB proteins, the GO term
      is equally appropriate. EB proteins autonomously track growing microtubule plus
      ends in vivo and exhibit high-resolution binding specificity for the transitional
      conformational states present at growing ends.
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-falcon.md
    supporting_text: 'EB/RP: Strongly appropriate. EB proteins autonomously bind the
      GTP-cap at plus ends and form tip comets in vitro and in vivo. CAP-Gly CLIPs:
      Appropriate but context-dependent. CLIP-170/CLIP1/2 bind plus ends primarily
      via EB-mediated hitchhiking; nonetheless, they physically localize to and bind
      plus ends in cells. XMAP215/ch-TOG: Strongly appropriate. XMAP215/ch-TOG/CKAP5
      localize to plus ends and act as polymerases; domain-level evidence links TOG5
      to tip tracking.'
taxonomic_scope:
  assessment: APPROPRIATE
  notes: 'Taxonomic targeting is generally appropriate: Condition Set 1 Glires (rodents,
    rabbits) is narrow but justified; Condition Set 2 Eukaryota is appropriately broad
    for conserved RP/EB proteins; Condition Set 3 Primates is narrow but justified
    for CLIP-associating proteins; Condition Set 4 Fungi is appropriate kingdom-level
    targeting; Condition Set 5 Dikarya is appropriate fungal subgroup. The multi-lineage
    approach reflects genuine evolutionary diversification of plus-end binding protein
    families. No evidence of inappropriate taxonomic over-restriction.'
  supported_by:
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-perplexity.md
    supporting_text: CAP-Gly domains and their tubulin-binding function are highly
      conserved across all eukaryotic lineages. CLIP-170 homologs exist in invertebrates
      (Drosophila melanogaster has orthologous CLIP-190). Fungi possess Bik1p, the
      S. cerevisiae ortholog of mammalian CLIP proteins, which shares essential structural
      features and functional capabilities. The S. pombe orthologs Tip1 and Bik1 also
      bind microtubules through CAP-Gly domains.
  - reference_id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-falcon.md
    supporting_text: 'Eukaryota: EB family is broadly conserved across eukaryotes,
      including yeasts (Bim1/Mal3) and vertebrates (EB1/2/3). Functional autonomy
      in tip tracking and GTP-cap recognition is conserved. Fungi/Dikarya: XMAP215
      family member Stu2 in budding yeast is a canonical plus-end actor; fungal EB
      homologs (Bim1) are autonomous +TIPs.'
suggested_modifications:
- Remove FunFam 2.30.30.190:FF:000002 from Condition Set 1 as it is 100% redundant
  with 2.30.30.190:FF:000001
- Remove FunFam 1.25.10.10:FF:000005 from Condition Set 3 as it is 100% redundant
  with 1.25.10.10:FF:000001
- Remove FunFam 1.20.5.1430:FF:000001 from Condition Set 2 as it is entirely contained
  within 1.10.418.10:FF:000007
- Consider adding annotation qualifiers or evidence codes reflecting the computational
  nature of this prediction
review_summary: 'ACCEPT with modifications. The core biological annotation is sound
  - these are bona fide microtubule plus-end binding proteins. However, the rule requires
  cleanup to remove redundant FunFams before deployment. After removing the three
  redundant/subset FunFams identified, this would be a well-structured rule capturing
  legitimate taxon-specific diversification of plus-end tracking protein families.

  '
rule:
  rule_id: ARBA00088058
  go_annotations:
  - go_id: GO:0051010
    go_label: microtubule plus-end binding
    aspect: MF
  condition_sets:
  - number: 1
    conditions:
    - condition_type: FUNFAM
      value: 2.30.30.190:FF:000001
      curie: CATH.FunFam:2.30.30.190:FF:000001
      label: Putative CAP-Gly domain-containing linker protein 1
      negated: false
    - condition_type: FUNFAM
      value: 2.30.30.190:FF:000002
      curie: CATH.FunFam:2.30.30.190:FF:000002
      label: CAP-Gly domain containing linker protein 1
      negated: false
    - condition_type: TAXON
      value: Glires
      curie: NCBITaxon:314147
      label: Glires
      negated: false
    notes: ''
    pairwise_overlap:
    - condition_a: 2.30.30.190:FF:000001
      condition_b: 2.30.30.190:FF:000002
      protein_database: SWISSPROT
      count_a: 7
      count_b: 7
      intersection_count: 7
      a_minus_b_count: 0
      b_minus_a_count: 0
      jaccard_similarity: 1.0
      containment_a_in_b: 1.0
      containment_b_in_a: 1.0
      interpretation: REDUNDANT
  - number: 2
    conditions:
    - condition_type: FUNFAM
      value: 1.10.418.10:FF:000007
      curie: CATH.FunFam:1.10.418.10:FF:000007
      label: Microtubule-associated protein, RP/EB family, member 2
      negated: false
    - condition_type: FUNFAM
      value: 1.20.5.1430:FF:000001
      curie: CATH.FunFam:1.20.5.1430:FF:000001
      label: microtubule-associated protein RP/EB family member 1
      negated: false
    - condition_type: TAXON
      value: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: ''
    pairwise_overlap:
    - condition_a: 1.10.418.10:FF:000007
      condition_b: 1.20.5.1430:FF:000001
      protein_database: SWISSPROT
      count_a: 19
      count_b: 9
      intersection_count: 9
      a_minus_b_count: 10
      b_minus_a_count: 0
      jaccard_similarity: 0.47368421052631576
      containment_a_in_b: 0.47368421052631576
      containment_b_in_a: 1.0
      interpretation: SUBSET
  - number: 3
    conditions:
    - condition_type: FUNFAM
      value: 1.25.10.10:FF:000001
      curie: CATH.FunFam:1.25.10.10:FF:000001
      label: CLIP-associating protein 1 isoform 2
      negated: false
    - condition_type: FUNFAM
      value: 1.25.10.10:FF:000005
      curie: CATH.FunFam:1.25.10.10:FF:000005
      label: CLIP-associating protein 1 isoform 2
      negated: false
    - condition_type: TAXON
      value: Primates
      curie: NCBITaxon:9443
      label: Primates
      negated: false
    notes: ''
    pairwise_overlap:
    - condition_a: 1.25.10.10:FF:000001
      condition_b: 1.25.10.10:FF:000005
      protein_database: SWISSPROT
      count_a: 9
      count_b: 9
      intersection_count: 9
      a_minus_b_count: 0
      b_minus_a_count: 0
      jaccard_similarity: 1.0
      containment_a_in_b: 1.0
      containment_b_in_a: 1.0
      interpretation: REDUNDANT
  - number: 4
    conditions:
    - condition_type: FUNFAM
      value: 1.10.418.10:FF:000028
      curie: CATH.FunFam:1.10.418.10:FF:000028
      label: RP/EB family microtubule-associated protein
      negated: false
    - condition_type: TAXON
      value: Fungi
      curie: NCBITaxon:4751
      label: Fungi
      negated: false
    notes: ''
  - number: 5
    conditions:
    - condition_type: FUNFAM
      value: 1.25.10.10:FF:000019
      curie: CATH.FunFam:1.25.10.10:FF:000019
      label: Cytoskeleton-associated protein 5
      negated: false
    - condition_type: TAXON
      value: Dikarya
      curie: NCBITaxon:451864
      label: Dikarya
      negated: false
    notes: ''
  entries:
  - id: 1.10.418.10:FF:000007
    type: FUNFAM
    label: Microtubule-associated protein, RP/EB family, member 2
    appears_in_condition_sets:
    - 2
    protein_count: 19
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000002
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: PREDICTED_BY
      target_id: 1.20.5.1430:FF:000001
      containment: 1.0
      jaccard_similarity: 0.474
      intersection_count: 9
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000005
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000028
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000019
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 1.0
      jaccard_similarity: 0.133
      intersection_count: 19
      exclusive_count: 0
  - id: 1.10.418.10:FF:000028
    type: FUNFAM
    label: RP/EB family microtubule-associated protein
    appears_in_condition_sets:
    - 4
    protein_count: 7
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000002
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.20.5.1430:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000005
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000019
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 0.571
      jaccard_similarity: 0.027
      intersection_count: 4
      exclusive_count: 3
  - id: 1.20.5.1430:FF:000001
    type: FUNFAM
    label: microtubule-associated protein RP/EB family member 1
    appears_in_condition_sets:
    - 2
    protein_count: 9
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000002
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: PREDICTS
      target_id: 1.10.418.10:FF:000007
      containment: 0.474
      jaccard_similarity: 0.474
      intersection_count: 9
      exclusive_count: 10
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000005
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000028
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000019
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 1.0
      jaccard_similarity: 0.063
      intersection_count: 9
      exclusive_count: 0
  - id: 1.25.10.10:FF:000001
    type: FUNFAM
    label: CLIP-associating protein 1 isoform 2
    appears_in_condition_sets:
    - 3
    protein_count: 9
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000002
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.20.5.1430:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000005
      containment: 1.0
      jaccard_similarity: 1.0
      intersection_count: 9
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000028
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000019
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 0.556
      jaccard_similarity: 0.034
      intersection_count: 5
      exclusive_count: 4
  - id: 1.25.10.10:FF:000005
    type: FUNFAM
    label: CLIP-associating protein 1 isoform 2
    appears_in_condition_sets:
    - 3
    protein_count: 9
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000002
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.20.5.1430:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000001
      containment: 1.0
      jaccard_similarity: 1.0
      intersection_count: 9
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000028
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000019
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 9
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 0.556
      jaccard_similarity: 0.034
      intersection_count: 5
      exclusive_count: 4
  - id: 1.25.10.10:FF:000019
    type: FUNFAM
    label: Cytoskeleton-associated protein 5
    appears_in_condition_sets:
    - 5
    protein_count: 10
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 10
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000002
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 10
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 10
    - relationship: EQUIV
      target_id: 1.20.5.1430:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 10
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 10
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000005
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 10
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000028
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 10
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 1.0
      jaccard_similarity: 0.07
      intersection_count: 10
      exclusive_count: 0
  - id: 2.30.30.190:FF:000001
    type: FUNFAM
    label: Putative CAP-Gly domain-containing linker protein 1
    appears_in_condition_sets:
    - 1
    protein_count: 7
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000002
      containment: 1.0
      jaccard_similarity: 1.0
      intersection_count: 7
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.20.5.1430:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000005
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000028
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000019
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 1.0
      jaccard_similarity: 0.049
      intersection_count: 7
      exclusive_count: 0
  - id: 2.30.30.190:FF:000002
    type: FUNFAM
    label: CAP-Gly domain containing linker protein 1
    appears_in_condition_sets:
    - 1
    protein_count: 7
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.30.190:FF:000001
      containment: 1.0
      jaccard_similarity: 1.0
      intersection_count: 7
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.20.5.1430:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000001
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000005
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.10.418.10:FF:000028
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 1.25.10.10:FF:000019
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 7
    - relationship: PREDICTS
      target_id: GO:0051010
      containment: 1.0
      jaccard_similarity: 0.049
      intersection_count: 7
      exclusive_count: 0
references:
- id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-perplexity.md
  title: Deep research analysis from Perplexity (microtubule plus-end binding)
  findings:
  - statement: CAP-Gly domains are specialized protein-interaction modules that bind
      C-terminal EEY/F motifs on alpha-tubulin
    supporting_text: CAP-Gly domains are specialized protein-interaction modules approximately
      50 amino acids in length that function as specific recognition elements for
      C-terminal sequences on tubulin proteins. The primary biological function of
      CAP-Gly domains is to bind with high specificity to the C-terminal EEY/F-COO⁻
      sequence motifs present on alpha-tubulin molecules. This binding interaction
      occurs through a conserved GKNDG motif present within the CAP-Gly domain structure
      itself, which makes direct contact with the C-terminal tyrosine residue of the
      α-tubulin E-hook.
  - statement: EB proteins autonomously track growing microtubule plus ends through
      recognition of GTP-cap
    supporting_text: End-binding proteins (EB1, EB2, EB3 in mammals) represent the
      most highly conserved and arguably most important constituents of the +TIP complex.
      These proteins possess an N-terminal calponin homology (CH) domain that directly
      recognizes the growing microtubule plus end, a linker region, and a C-terminal
      coiled-coil domain essential for dimerization. Critically, EB proteins have
      the intrinsic ability to bind and track growing microtubule plus ends autonomously,
      without requiring interaction with other +TIP proteins.
  - statement: CLIP-170 requires EB1 for efficient plus-end localization as a hitchhiker
      +TIP
    supporting_text: CLIP-170 associates with microtubule plus ends in vivo through
      its interaction with EB1, a core +TIP protein. Single-molecule tracking studies
      show that CLIP-170 exchanges rapidly at growing microtubule plus ends, consistent
      with dynamic plus-end tracking rather than stable lattice binding. The requirement
      for EB1 in CLIP-170 plus-end localization indicates that CLIP-170 does not autonomously
      track plus ends but rather is recruited through interaction with the primary
      +TIP complex.
  - statement: CLASP proteins stabilize pre-catastrophe intermediate states at microtubule
      ends
    supporting_text: The mechanism by which CLASPs regulate microtubule dynamics involves
      stabilization of a nucleotide-dependent intermediate state at the microtubule
      end. CLASPs specifically stabilize the pre-catastrophe intermediate state between
      growth and shrinkage, thereby suppressing microtubule catastrophe and promoting
      microtubule rescue.
  - statement: XMAP215/ch-TOG family proteins act as processive microtubule polymerases
      at plus ends
    supporting_text: 'CKAP5 (cytoskeleton-associated protein 5) represents a distinct
      functional category among plus-end-binding proteins: CKAP5 acts as a processive
      microtubule polymerase. CKAP5 binds to the plus end of microtubules and regulates
      microtubule dynamics and organization while acting as a processive microtubule
      polymerase. The polymerase activity of CKAP5 places this protein in the XMAP215/Stu2
      family of microtubule regulators.'
- id: file:rules/arba/ARBA00088058/ARBA00088058-deep-research-falcon.md
  title: Deep research analysis from Falcon (microtubule plus-end binding)
  findings:
  - statement: EB proteins recognize GTP-like cap at plus ends with paralog-specific
      differences in affinity
    supporting_text: 'EB/RP family (EB1/EB2/EB3; yeast Bim1/Mal3): Autonomous +TIPs
      that bind the GTP-like cap at growing microtubule plus-ends, forming characteristic
      comets, recruiting SxIP-motif partners and CAP-Gly proteins via EBH/EEY modules,
      and modulating dynamics. Differences among paralogs: EB3 > EB1 > EB2 in plus-end
      affinity; EB2 cannot fully rescue EB1/EB3 functions.'
  - statement: CAP-Gly CLIPs are hitchhiker +TIPs dependent on EB for robust tip localization
    supporting_text: 'CAP-Gly CLIPs (CLIP-170/CLIP1/CLIP2): CAP-Gly +TIPs that localize
      to plus ends primarily by hitchhiking on EB proteins through EEY–CAP-Gly recognition;
      they link growing ends to organelles, motors (e.g., dynein initiation), and
      signaling complexes. Classic in vivo imaging demonstrates CLIP-170 tracks growing
      ends. Dependence on EB for robust tip localization is typical.'
  - statement: XMAP215/ch-TOG family members use TOG domains for tip tracking and
      polymerase activity
    supporting_text: 'XMAP215/ch-TOG family (CKAP5/ch-TOG/XMAP215; yeast Stu2): Autonomous
      +TIP microtubule polymerases that bind curved tubulin at the very tip to accelerate
      polymerization; also cooperate with γ-TuRC in nucleation. Plus-end localization
      and polymerase activity are hallmarks. Arrays of TOG domains (HEAT repeats).
      Domain specialization: TOG5 mediates plus-end/lattice engagement and tip tracking;
      TOG1–4 recruit soluble tubulin; TOG6 and a C-terminal region bind γ-TuRC/γ-tubulin
      to promote nucleation.'