DPYSL2

UniProt ID: Q16555
Organism: Homo sapiens
Review Status: DRAFT
Aliases:
CRMP2 CRMP-2 DRP-2 ULIP-2 TOAD-64 Collapsin response mediator protein 2
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Gene Description

Dihydropyrimidinase-related protein 2 (DPYSL2/CRMP2), a brain-enriched cytoplasmic protein of the collapsin-response-mediator (CRMP) / dihydropyrimidinase family. Although it belongs to the metallo-dependent hydrolase superfamily, it lacks the conserved metal-cofactor-binding residues and has no dihydropyrimidinase activity - it is a catalytically dead family member. CRMP2 is a key cytoskeletal regulator in semaphorin-3A signaling: it binds tubulin heterodimers to promote microtubule assembly and axon specification/growth, mediates growth-cone collapse and neuronal polarity, and is inactivated by GSK3B/CDK5/ROCK phosphorylation. It forms homo- and hetero-tetramers with other CRMPs and also participates in vesicle/endocytic trafficking.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005829 cytosol
IBA
GO_REF:0000033
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0006208 pyrimidine nucleobase catabolic process
IBA NOT
GO_REF:0000033
ACCEPT
Summary: NOT: DPYSL2 is not involved in pyrimidine nucleobase catabolism (the process counterpart of the absent dihydropyrimidinase activity).
Reason: Correct negation, consistent with loss of catalytic activity. Retain.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Lacks most of the conserved residues that are essential for
GO:0016812 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides
IBA
GO_REF:0000033
REMOVE
Summary: Positive 'hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides' propagated from the metallo-hydrolase fold signature (IBA). DPYSL2 lacks the catalytic metal site, and the curated dihydropyrimidinase activity is itself NOT-ed.
Reason: Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Lacks most of the conserved residues that are essential for
file:human/DPYSL2/DPYSL2-uniprot.txt
Belongs to the metallo-dependent hydrolases superfamily.
GO:0004157 dihydropyrimidinase activity
IBA NOT
GO_REF:0000033
ACCEPT
Summary: NOT: DPYSL2 does not have dihydropyrimidinase activity. It belongs to the metallo-dependent hydrolase superfamily but lacks the conserved metal-cofactor-binding residues required for catalysis (UniProt CAUTION).
Reason: Correct, important negation: a catalytically dead family member. Retain.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Lacks most of the conserved residues that are essential for
GO:0005737 cytoplasm
IEA
GO_REF:0000002
ACCEPT
Summary: cytoplasm: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005829 cytosol
IEA
GO_REF:0000044
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005856 cytoskeleton
IEA
GO_REF:0000044
ACCEPT
Summary: cytoskeleton: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0016020 membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: membrane: a secondary/broad or context-specific localization for DPYSL2.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0016787 hydrolase activity
IEA
GO_REF:0000002
REMOVE
Summary: Positive 'hydrolase activity' propagated from the metallo-hydrolase fold signature (IEA). DPYSL2 lacks the catalytic metal site, and the curated dihydropyrimidinase activity is itself NOT-ed.
Reason: Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Lacks most of the conserved residues that are essential for
file:human/DPYSL2/DPYSL2-uniprot.txt
Belongs to the metallo-dependent hydrolases superfamily.
GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
IEA
GO_REF:0000002
REMOVE
Summary: Positive 'hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds' propagated from the metallo-hydrolase fold signature (IEA). DPYSL2 lacks the catalytic metal site, and the curated dihydropyrimidinase activity is itself NOT-ed.
Reason: Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Lacks most of the conserved residues that are essential for
file:human/DPYSL2/DPYSL2-uniprot.txt
Belongs to the metallo-dependent hydrolases superfamily.
GO:0005515 protein binding
IPI
PMID:21900206
A directed protein interaction network for investigating int...
KEEP AS NON CORE
Summary: Specific protein interaction (PMID:21900206); supports DPYSL2's scaffold/adapter role but the generic 'protein binding' term is uninformative.
Reason: Real interaction kept as non-core supporting evidence; the informative function is captured in core_functions.
GO:0005515 protein binding
IPI
PMID:24722188
Protein interaction network of alternatively spliced isoform...
KEEP AS NON CORE
Summary: Specific protein interaction (PMID:24722188); supports DPYSL2's scaffold/adapter role but the generic 'protein binding' term is uninformative.
Reason: Real interaction kept as non-core supporting evidence; the informative function is captured in core_functions.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:25416956).
Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun...
MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:28514442).
Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding
IPI
PMID:29892012
An interactome perturbation framework prioritizes damaging m...
MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:29892012).
Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:31515488).
Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32296183).
Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32814053).
Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:33961781).
Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding
IPI
PMID:36950384
Protein interaction studies in human induced neurons indicat...
KEEP AS NON CORE
Summary: Specific protein interaction (PMID:36950384); supports DPYSL2's scaffold/adapter role but the generic 'protein binding' term is uninformative.
Reason: Real interaction kept as non-core supporting evidence; the informative function is captured in core_functions.
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
KEEP AS NON CORE
Summary: Specific protein interaction (PMID:40205054); supports DPYSL2's scaffold/adapter role but the generic 'protein binding' term is uninformative.
Reason: Real interaction kept as non-core supporting evidence; the informative function is captured in core_functions.
GO:0042802 identical protein binding
IPI
PMID:21516116
Next-generation sequencing to generate interactome datasets.
KEEP AS NON CORE
Summary: Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family members.
Reason: Real oligomerization but a generic term; non-core.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Homotetramer
GO:0042802 identical protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
KEEP AS NON CORE
Summary: Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family members.
Reason: Real oligomerization but a generic term; non-core.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Homotetramer
GO:0042802 identical protein binding
IPI
PMID:29892012
An interactome perturbation framework prioritizes damaging m...
KEEP AS NON CORE
Summary: Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family members.
Reason: Real oligomerization but a generic term; non-core.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Homotetramer
GO:0042802 identical protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
KEEP AS NON CORE
Summary: Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family members.
Reason: Real oligomerization but a generic term; non-core.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Homotetramer
GO:0042802 identical protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family members.
Reason: Real oligomerization but a generic term; non-core.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Homotetramer
GO:0005829 cytosol
IDA
GO_REF:0000052
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0015630 microtubule cytoskeleton
IDA
GO_REF:0000052
ACCEPT
Summary: microtubule cytoskeleton: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0045171 intercellular bridge
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: intercellular bridge: a secondary/broad or context-specific localization for DPYSL2.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0072686 mitotic spindle
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: mitotic spindle: a secondary/broad or context-specific localization for DPYSL2.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0005829 cytosol
IDA
PMID:20801876
Collapsin response mediator protein-2 (Crmp2) regulates traf...
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005874 microtubule
IDA
PMID:20801876
Collapsin response mediator protein-2 (Crmp2) regulates traf...
ACCEPT
Summary: microtubule: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0006897 endocytosis
IMP
PMID:20801876
Collapsin response mediator protein-2 (Crmp2) regulates traf...
KEEP AS NON CORE
Summary: endocytosis: a broader/secondary process for DPYSL2.
Reason: Valid but non-core relative to the cytoskeletal-regulation function.
GO:0016020 membrane
IDA
PMID:20801876
Collapsin response mediator protein-2 (Crmp2) regulates traf...
KEEP AS NON CORE
Summary: membrane: a secondary/broad or context-specific localization for DPYSL2.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0070062 extracellular exosome
HDA
PMID:20458337
MHC class II-associated proteins in B-cell exosomes and pote...
KEEP AS NON CORE
Summary: extracellular exosome: a secondary/broad or context-specific localization for DPYSL2.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0005829 cytosol
TAS
Reactome:R-HSA-399951
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005829 cytosol
TAS
Reactome:R-HSA-399944
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005829 cytosol
TAS
Reactome:R-HSA-399947
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005829 cytosol
TAS
Reactome:R-HSA-443783
ACCEPT
Summary: cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005515 protein binding
IPI
PMID:19235893
Protein product of CLN6 gene responsible for variant late-on...
KEEP AS NON CORE
Summary: Specific protein interaction (PMID:19235893); supports DPYSL2's scaffold/adapter role but the generic 'protein binding' term is uninformative.
Reason: Real interaction kept as non-core supporting evidence; the informative function is captured in core_functions.
GO:0007010 cytoskeleton organization
ISS
GO_REF:0000024
ACCEPT
Summary: cytoskeleton organization: a core neuronal/cytoskeletal process for the CRMP family (DPYSL2 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0005515 protein binding
IPI
PMID:16260607
CRMP-2 is involved in kinesin-1-dependent transport of the S...
KEEP AS NON CORE
Summary: Specific protein interaction (PMID:16260607); supports DPYSL2's scaffold/adapter role but the generic 'protein binding' term is uninformative.
Reason: Real interaction kept as non-core supporting evidence; the informative function is captured in core_functions.
GO:0004157 dihydropyrimidinase activity
TAS
PMID:8973361
A novel gene family defined by human dihydropyrimidinase and...
REMOVE
Summary: Legacy positive dihydropyrimidinase activity (TAS, PMID:8973361) from an early report, superseded by the finding that DPYSL2 lacks the catalytic metal-binding residues.
Reason: Outdated enzymatic claim, contradicted by the UniProt CAUTION and the curated NOT|dihydropyrimidinase. Remove (legacy mis-annotation).
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Lacks most of the conserved residues that are essential for
GO:0006139 nucleobase-containing compound metabolic process
TAS
PMID:8973361
A novel gene family defined by human dihydropyrimidinase and...
REMOVE
Summary: Nucleobase-containing compound metabolic process (TAS, PMID:8973361) tied to the now-defunct dihydropyrimidinase activity claim.
Reason: Legacy process annotation dependent on the superseded enzymatic activity; remove, consistent with the NOT|pyrimidine catabolism.
Supporting Evidence:
file:human/DPYSL2/DPYSL2-uniprot.txt
Lacks most of the conserved residues that are essential for
GO:0007165 signal transduction
TAS
PMID:8973361
A novel gene family defined by human dihydropyrimidinase and...
KEEP AS NON CORE
Summary: signal transduction: a broader/secondary process for DPYSL2.
Reason: Valid but non-core relative to the cytoskeletal-regulation function.
GO:0007399 nervous system development
TAS
PMID:8973361
A novel gene family defined by human dihydropyrimidinase and...
ACCEPT
Summary: nervous system development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL2 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.

Core Functions

Catalytically inactive CRMP-family cytoskeletal regulator that binds tubulin and promotes microtubule assembly to drive axon growth, neuronal polarity and semaphorin-3A-induced growth-cone dynamics; phosphoregulated by GSK3B/CDK5/ROCK.

Supporting Evidence:
  • file:human/DPYSL2/DPYSL2-uniprot.txt
    Lacks most of the conserved residues that are essential for

References

GO annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified annotations to orthologs by curator judgment
Annotation inferences using phylogenetic trees
GO annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
GO annotation based on curation of immunofluorescence data (HPA)
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
file:human/DPYSL2/DPYSL2-uniprot.txt
UniProt entry for DPYSL2
  • DPYSL2 lacks the metal-cofactor-binding residues required for dihydropyrimidinase activity.
    "Lacks most of the conserved residues that are essential for"
  • DPYSL2 belongs to the metallo-dependent hydrolase superfamily.
    "Belongs to the metallo-dependent hydrolases superfamily."
CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation.
Protein product of CLN6 gene responsible for variant late-onset infantile neuronal ceroid lipofuscinosis interacts with CRMP-2.
MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking endocytic regulatory proteins to dynein motors.
Next-generation sequencing to generate interactome datasets.
A directed protein interaction network for investigating intracellular signal transduction.
Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.
A proteome-scale map of the human interactome network.
Architecture of the human interactome defines protein communities and disease networks.
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.
Multimodal cell maps as a foundation for structural and functional genomics.
A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution.
Reactome:R-HSA-399944
Reactome pathway (CRMP/semaphorin signalling)
Reactome:R-HSA-399947
Reactome pathway (CRMP/semaphorin signalling)
Reactome:R-HSA-399951
Reactome pathway (CRMP/semaphorin signalling)
Reactome:R-HSA-443783
Reactome pathway (CRMP/semaphorin signalling)

Suggested Questions for Experts

Q: How does CRMP2 (DPYSL2) select tubulin heterodimers to promote microtubule assembly, and how do sequential GSK3B/CDK5/ROCK phosphorylations switch this binding off during semaphorin-3A-induced growth-cone collapse?

Suggested Experiments

Experiment: Reconstitute microtubule assembly with purified CRMP2 phospho-mimetic/phospho-dead variants and measure tubulin-heterodimer binding and axon outgrowth in neurons.

Hypothesis: Map the CRMP2 phospho-states that toggle tubulin binding.

📄 View Raw YAML

# yaml-language-server: $schema=../../../src/ai_gene_review/schema/gene_review.yaml
id: Q16555
gene_symbol: DPYSL2
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'Dihydropyrimidinase-related protein 2 (DPYSL2/CRMP2), a brain-enriched cytoplasmic protein
  of the collapsin-response-mediator (CRMP) / dihydropyrimidinase family. Although it belongs to the metallo-dependent
  hydrolase superfamily, it lacks the conserved metal-cofactor-binding residues and has no dihydropyrimidinase
  activity - it is a catalytically dead family member. CRMP2 is a key cytoskeletal regulator in semaphorin-3A
  signaling: it binds tubulin heterodimers to promote microtubule assembly and axon specification/growth,
  mediates growth-cone collapse and neuronal polarity, and is inactivated by GSK3B/CDK5/ROCK phosphorylation.
  It forms homo- and hetero-tetramers with other CRMPs and also participates in vesicle/endocytic trafficking.'
alternative_products:
- name: '1'
  id: Q16555-1
- name: '2'
  id: Q16555-2
  sequence_note: VSP_044941
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0006208
    label: pyrimidine nucleobase catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  negated: true
  review:
    summary: 'NOT: DPYSL2 is not involved in pyrimidine nucleobase catabolism (the process counterpart
      of the absent dihydropyrimidinase activity).'
    action: ACCEPT
    reason: Correct negation, consistent with loss of catalytic activity. Retain.
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
- term:
    id: GO:0016812
    label: hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Positive 'hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic
      amides' propagated from the metallo-hydrolase fold signature (IBA). DPYSL2 lacks the catalytic metal
      site, and the curated dihydropyrimidinase activity is itself NOT-ed.
    action: REMOVE
    reason: 'Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding
      residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function
      is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.'
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Belongs to the metallo-dependent hydrolases superfamily.
- term:
    id: GO:0004157
    label: dihydropyrimidinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  negated: true
  review:
    summary: 'NOT: DPYSL2 does not have dihydropyrimidinase activity. It belongs to the metallo-dependent
      hydrolase superfamily but lacks the conserved metal-cofactor-binding residues required for catalysis
      (UniProt CAUTION).'
    action: ACCEPT
    reason: 'Correct, important negation: a catalytically dead family member. Retain.'
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: 'cytoplasm: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'cytoskeleton: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'membrane: a secondary/broad or context-specific localization for DPYSL2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0016787
    label: hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Positive 'hydrolase activity' propagated from the metallo-hydrolase fold signature (IEA).
      DPYSL2 lacks the catalytic metal site, and the curated dihydropyrimidinase activity is itself NOT-ed.
    action: REMOVE
    reason: 'Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding
      residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function
      is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.'
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Belongs to the metallo-dependent hydrolases superfamily.
- term:
    id: GO:0016810
    label: hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Positive 'hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds' propagated
      from the metallo-hydrolase fold signature (IEA). DPYSL2 lacks the catalytic metal site, and the
      curated dihydropyrimidinase activity is itself NOT-ed.
    action: REMOVE
    reason: 'Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding
      residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function
      is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.'
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Belongs to the metallo-dependent hydrolases superfamily.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21900206
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:21900206); supports DPYSL2's scaffold/adapter role but
      the generic 'protein binding' term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the informative function is captured
      in core_functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24722188
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:24722188); supports DPYSL2's scaffold/adapter role but
      the generic 'protein binding' term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the informative function is captured
      in core_functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:25416956).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:28514442).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:29892012).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:31515488).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32296183).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32814053).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:33961781).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36950384
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:36950384); supports DPYSL2's scaffold/adapter role but
      the generic 'protein binding' term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the informative function is captured
      in core_functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:40205054); supports DPYSL2's scaffold/adapter role but
      the generic 'protein binding' term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the informative function is captured
      in core_functions.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  qualifier: enables
  review:
    summary: 'Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family
      members.'
    action: KEEP_AS_NON_CORE
    reason: Real oligomerization but a generic term; non-core.
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Homotetramer
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: 'Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family
      members.'
    action: KEEP_AS_NON_CORE
    reason: Real oligomerization but a generic term; non-core.
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Homotetramer
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  qualifier: enables
  review:
    summary: 'Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family
      members.'
    action: KEEP_AS_NON_CORE
    reason: Real oligomerization but a generic term; non-core.
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Homotetramer
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: 'Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family
      members.'
    action: KEEP_AS_NON_CORE
    reason: Real oligomerization but a generic term; non-core.
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Homotetramer
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: 'Identical protein binding: DPYSL2 forms homo- and hetero-tetramers with other CRMP-family
      members.'
    action: KEEP_AS_NON_CORE
    reason: Real oligomerization but a generic term; non-core.
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Homotetramer
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0015630
    label: microtubule cytoskeleton
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'microtubule cytoskeleton: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal
      CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0045171
    label: intercellular bridge
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'intercellular bridge: a secondary/broad or context-specific localization for DPYSL2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0072686
    label: mitotic spindle
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'mitotic spindle: a secondary/broad or context-specific localization for DPYSL2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:20801876
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IDA
  original_reference_id: PMID:20801876
  qualifier: colocalizes_with
  review:
    summary: 'microtubule: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0006897
    label: endocytosis
  evidence_type: IMP
  original_reference_id: PMID:20801876
  qualifier: involved_in
  review:
    summary: 'endocytosis: a broader/secondary process for DPYSL2.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core relative to the cytoskeletal-regulation function.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:20801876
  qualifier: colocalizes_with
  review:
    summary: 'membrane: a secondary/broad or context-specific localization for DPYSL2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: 'extracellular exosome: a secondary/broad or context-specific localization for DPYSL2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-399951
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-399944
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-399947
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-443783
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL2 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19235893
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:19235893); supports DPYSL2's scaffold/adapter role but
      the generic 'protein binding' term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the informative function is captured
      in core_functions.
- term:
    id: GO:0007010
    label: cytoskeleton organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'cytoskeleton organization: a core neuronal/cytoskeletal process for the CRMP family (DPYSL2
      acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).'
    action: ACCEPT
    reason: Core biological process for a CRMP-family cytoskeletal regulator.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16260607
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:16260607); supports DPYSL2's scaffold/adapter role but
      the generic 'protein binding' term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the informative function is captured
      in core_functions.
- term:
    id: GO:0004157
    label: dihydropyrimidinase activity
  evidence_type: TAS
  original_reference_id: PMID:8973361
  qualifier: enables
  review:
    summary: Legacy positive dihydropyrimidinase activity (TAS, PMID:8973361) from an early report, superseded
      by the finding that DPYSL2 lacks the catalytic metal-binding residues.
    action: REMOVE
    reason: Outdated enzymatic claim, contradicted by the UniProt CAUTION and the curated NOT|dihydropyrimidinase.
      Remove (legacy mis-annotation).
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
- term:
    id: GO:0006139
    label: nucleobase-containing compound metabolic process
  evidence_type: TAS
  original_reference_id: PMID:8973361
  qualifier: involved_in
  review:
    summary: Nucleobase-containing compound metabolic process (TAS, PMID:8973361) tied to the now-defunct
      dihydropyrimidinase activity claim.
    action: REMOVE
    reason: Legacy process annotation dependent on the superseded enzymatic activity; remove, consistent
      with the NOT|pyrimidine catabolism.
    supported_by:
    - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: TAS
  original_reference_id: PMID:8973361
  qualifier: involved_in
  review:
    summary: 'signal transduction: a broader/secondary process for DPYSL2.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core relative to the cytoskeletal-regulation function.
- term:
    id: GO:0007399
    label: nervous system development
  evidence_type: TAS
  original_reference_id: PMID:8973361
  qualifier: involved_in
  review:
    summary: 'nervous system development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL2
      acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).'
    action: ACCEPT
    reason: Core biological process for a CRMP-family cytoskeletal regulator.
references:
- id: GO_REF:0000002
  title: GO annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified annotations to orthologs by curator judgment
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: GO annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: GO annotation based on curation of immunofluorescence data (HPA)
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
    Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/DPYSL2/DPYSL2-uniprot.txt
  title: UniProt entry for DPYSL2
  findings:
  - statement: DPYSL2 lacks the metal-cofactor-binding residues required for dihydropyrimidinase activity.
    supporting_text: Lacks most of the conserved residues that are essential for
  - statement: DPYSL2 belongs to the metallo-dependent hydrolase superfamily.
    supporting_text: Belongs to the metallo-dependent hydrolases superfamily.
- id: PMID:16260607
  title: CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation.
  findings: []
- id: PMID:19235893
  title: Protein product of CLN6 gene responsible for variant late-onset infantile neuronal ceroid lipofuscinosis
    interacts with CRMP-2.
  findings: []
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional implications for
    exosome biogenesis.
  findings: []
- id: PMID:20801876
  title: Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking endocytic regulatory
    proteins to dynein motors.
  findings: []
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  findings: []
- id: PMID:21900206
  title: A directed protein interaction network for investigating intracellular signal transduction.
  findings: []
- id: PMID:24722188
  title: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors
    for autism.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:29892012
  title: An interactome perturbation framework prioritizes damaging missense mutations for developmental
    disorders.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency
    spectrum in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread
    Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:36950384
  title: Protein interaction studies in human induced neurons indicate convergent biology underlying autism
    spectrum disorders.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:8973361
  title: A novel gene family defined by human dihydropyrimidinase and three related proteins with differential
    tissue distribution.
  findings: []
- id: Reactome:R-HSA-399944
  title: Reactome pathway (CRMP/semaphorin signalling)
  findings: []
- id: Reactome:R-HSA-399947
  title: Reactome pathway (CRMP/semaphorin signalling)
  findings: []
- id: Reactome:R-HSA-399951
  title: Reactome pathway (CRMP/semaphorin signalling)
  findings: []
- id: Reactome:R-HSA-443783
  title: Reactome pathway (CRMP/semaphorin signalling)
  findings: []
aliases:
- CRMP2
- CRMP-2
- DRP-2
- ULIP-2
- TOAD-64
- Collapsin response mediator protein 2
core_functions:
- description: Catalytically inactive CRMP-family cytoskeletal regulator that binds tubulin and promotes
    microtubule assembly to drive axon growth, neuronal polarity and semaphorin-3A-induced growth-cone
    dynamics; phosphoregulated by GSK3B/CDK5/ROCK.
  directly_involved_in:
  - id: GO:0007399
    label: nervous system development
  - id: GO:0007010
    label: cytoskeleton organization
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0015630
    label: microtubule cytoskeleton
  supported_by:
  - reference_id: file:human/DPYSL2/DPYSL2-uniprot.txt
    supporting_text: Lacks most of the conserved residues that are essential for
suggested_questions:
- question: How does CRMP2 (DPYSL2) select tubulin heterodimers to promote microtubule assembly, and how
    do sequential GSK3B/CDK5/ROCK phosphorylations switch this binding off during semaphorin-3A-induced
    growth-cone collapse?
suggested_experiments:
- hypothesis: Map the CRMP2 phospho-states that toggle tubulin binding.
  description: Reconstitute microtubule assembly with purified CRMP2 phospho-mimetic/phospho-dead variants
    and measure tubulin-heterodimer binding and axon outgrowth in neurons.