View original ARBA rule on UniProt
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.
Condition-set counts describe the sets recorded in this review, which may omit the full rule.
Interactive prediction matrix showing how row entries PREDICT column entries. Cell (i,j) shows what fraction of proteins with row domain i also have column domain j. Click cells to view intersection in UniProt. Click domain IDs to view proteins with that domain.
Legend: Each cell shows PREDICTS % (fraction of row entry proteins that also have column entry - row PREDICTS column), Jaccard similarity (J:%), and intersection count. CS = Condition Set(s), TGT = GO annotation target.
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.
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.
| Condition A | Condition B | Count A | Count B | Intersection | Jaccard | A in B | B in A | Interpretation |
|---|---|---|---|---|---|---|---|---|
2.30.30.190:FF:000001
|
2.30.30.190:FF:000002
|
7 | 7 | 7 | 1.000 | 1.000 | 1.000 | REDUNDANT |
| Condition A | Condition B | Count A | Count B | Intersection | Jaccard | A in B | B in A | Interpretation |
|---|---|---|---|---|---|---|---|---|
1.10.418.10:FF:000007
|
1.20.5.1430:FF:000001
|
19 | 9 | 9 | 0.474 | 0.474 | 1.000 | SUBSET |
| Condition A | Condition B | Count A | Count B | Intersection | Jaccard | A in B | B in A | Interpretation |
|---|---|---|---|---|---|---|---|---|
1.25.10.10:FF:000001
|
1.25.10.10:FF:000005
|
9 | 9 | 9 | 1.000 | 1.000 | 1.000 | REDUNDANT |
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.
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.
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.
The GO term microtubule plus-end binding is appropriate for these protein families
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.
CAP-Gly domains are specialized protein-interaction modules that bind C-terminal EEY/F motifs on alpha-tubulin
EB proteins autonomously track growing microtubule plus ends through recognition of GTP-cap
CLIP-170 requires EB1 for efficient plus-end localization as a hitchhiker +TIP
CLASP proteins stabilize pre-catastrophe intermediate states at microtubule ends
XMAP215/ch-TOG family proteins act as processive microtubule polymerases at plus ends
EB proteins recognize GTP-like cap at plus ends with paralog-specific differences in affinity
CAP-Gly CLIPs are hitchhiker +TIPs dependent on EB for robust tip localization
XMAP215/ch-TOG family members use TOG domains for tip tracking and polymerase activity
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
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target_id: 1.25.10.10:FF:000001
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target_id: 1.25.10.10:FF:000005
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target_id: 1.10.418.10:FF:000028
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target_id: GO:0051010
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- 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:
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target_id: 2.30.30.190:FF:000002
containment: 1.0
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target_id: 1.10.418.10:FF:000007
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target_id: 1.20.5.1430:FF:000001
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target_id: GO:0051010
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- 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:
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target_id: 2.30.30.190:FF:000001
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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.'