DPYSL3

UniProt ID: Q14195
Organism: Homo sapiens
Review Status: DRAFT
Aliases:
CRMP4 CRMP-4 DRP-3 ULIP-1 Collapsin response mediator protein 4
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Gene Description

Dihydropyrimidinase-related protein 3 (DPYSL3/CRMP4), a cytoplasmic CRMP-family protein required for class-3 semaphorin signaling and cytoskeletal remodeling. A catalytically dead member of the metallo-dependent hydrolase (dihydropyrimidinase) superfamily, it lacks the conserved metal-cofactor residues and has no dihydropyrimidinase activity. DPYSL3 is distinguished by F-actin binding/bundling and filopodium regulation, binds filamin and chondroitin sulfate, and modulates neuron projection development, growth-cone dynamics and cell migration. It forms homo- and hetero-tetramers with other CRMPs.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005829 cytosol
IBA
GO_REF:0000033 		ACCEPT
Summary: cytosol: a core subcellular location for DPYSL3 (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: DPYSL3 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/DPYSL3/DPYSL3-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). DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
Lacks most of the conserved residues that are essential for
file:human/DPYSL3/DPYSL3-uniprot.txt
Belongs to the metallo-dependent hydrolases superfamily.
GO:0004157 dihydropyrimidinase activity
IBA NOT
GO_REF:0000033 		ACCEPT
Summary: NOT: DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
Lacks most of the conserved residues that are essential for
GO:0051764 actin crosslink formation
IBA
GO_REF:0000033 		ACCEPT
Summary: actin crosslink formation: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		ACCEPT
Summary: cytoplasm: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0016787 hydrolase activity
IEA
GO_REF:0000002 		REMOVE
Summary: Positive 'hydrolase activity' propagated from the metallo-hydrolase fold signature (IEA). DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
Lacks most of the conserved residues that are essential for
file:human/DPYSL3/DPYSL3-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). DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
Lacks most of the conserved residues that are essential for
file:human/DPYSL3/DPYSL3-uniprot.txt
Belongs to the metallo-dependent hydrolases superfamily.
GO:0030426 growth cone
IEA
GO_REF:0000120 		ACCEPT
Summary: growth cone: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005515 protein binding
IPI
PMID:21044950
Genome-wide YFP fluorescence complementation screen identifi... 		KEEP AS NON CORE
Summary: Specific protein interaction (PMID:21044950); supports DPYSL3'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: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: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
Q14195-2
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
Q14195-2
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:0005576 extracellular region
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: extracellular region: a secondary/broad or context-specific localization for DPYSL3.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0005829 cytosol
IEA
GO_REF:0000107 		ACCEPT
Summary: cytosol: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0010976 positive regulation of neuron projection development
IEA
GO_REF:0000107 		ACCEPT
Summary: positive regulation of neuron projection development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0010977 negative regulation of neuron projection development
IEA
GO_REF:0000107 		ACCEPT
Summary: negative regulation of neuron projection development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0017124 SH3 domain binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: SH3 domain binding: a specific molecular interaction consistent with DPYSL3's cytoskeletal-adapter role.
Reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function. Non-core.
GO:0030027 lamellipodium
IEA
GO_REF:0000107 		ACCEPT
Summary: lamellipodium: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0030336 negative regulation of cell migration
IEA
GO_REF:0000107 		ACCEPT
Summary: negative regulation of cell migration: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0031941 filamentous actin
IEA
GO_REF:0000107 		ACCEPT
Summary: filamentous actin: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0035374 chondroitin sulfate binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: chondroitin sulfate binding: a specific molecular interaction consistent with DPYSL3's cytoskeletal-adapter role.
Reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function. Non-core.
GO:0042802 identical protein binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Identical protein binding: DPYSL3 forms homo- and hetero-tetramers with other CRMP-family members.
Reason: Real oligomerization but a generic term; non-core.
Supporting Evidence:
file:human/DPYSL3/DPYSL3-uniprot.txt
Homotetramer
GO:0044297 cell body
IEA
GO_REF:0000107 		ACCEPT
Summary: cell body: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0045202 synapse
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: synapse: a secondary/broad or context-specific localization for DPYSL3.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0048666 neuron development
IEA
GO_REF:0000107 		ACCEPT
Summary: neuron development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0051017 actin filament bundle assembly
IEA
GO_REF:0000107 		ACCEPT
Summary: actin filament bundle assembly: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0051219 phosphoprotein binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: phosphoprotein binding: a specific molecular interaction consistent with DPYSL3's cytoskeletal-adapter role.
Reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function. Non-core.
GO:0051491 positive regulation of filopodium assembly
IEA
GO_REF:0000107 		ACCEPT
Summary: positive regulation of filopodium assembly: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0051764 actin crosslink formation
IEA
GO_REF:0000107 		ACCEPT
Summary: actin crosslink formation: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0070382 exocytic vesicle
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: exocytic vesicle: a secondary/broad or context-specific localization for DPYSL3.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0042802 identical protein binding
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Identical protein binding: DPYSL3 forms homo- and hetero-tetramers with other CRMP-family members.
Reason: Real oligomerization but a generic term; non-core.
Supporting Evidence:
file:human/DPYSL3/DPYSL3-uniprot.txt
Homotetramer
GO:0031005 filamin binding
IPI
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact w... 		ACCEPT
Summary: filamin binding: a specific molecular interaction consistent with DPYSL3's cytoskeletal-adapter role.
Reason: Filamin binding is a specific, experimentally demonstrated interaction (PMID:25358863) central to this CRMP's cytoskeletal-adapter role; retained as the representative core binding molecular function.
GO:0005829 cytosol
TAS
Reactome:R-HSA-399951 		ACCEPT
Summary: cytosol: a core subcellular location for DPYSL3 (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 DPYSL3 (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 DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0005576 extracellular region
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: extracellular region: a secondary/broad or context-specific localization for DPYSL3.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0005829 cytosol
ISS
GO_REF:0000024 		ACCEPT
Summary: cytosol: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0010976 positive regulation of neuron projection development
ISS
GO_REF:0000024 		ACCEPT
Summary: positive regulation of neuron projection development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0010977 negative regulation of neuron projection development
ISS
GO_REF:0000024 		ACCEPT
Summary: negative regulation of neuron projection development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0017124 SH3 domain binding
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: SH3 domain binding: a specific molecular interaction consistent with DPYSL3's cytoskeletal-adapter role.
Reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function. Non-core.
GO:0030027 lamellipodium
ISS
GO_REF:0000024 		ACCEPT
Summary: lamellipodium: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0030336 negative regulation of cell migration
ISS
GO_REF:0000024 		ACCEPT
Summary: negative regulation of cell migration: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0030426 growth cone
ISS
GO_REF:0000024 		ACCEPT
Summary: growth cone: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0031941 filamentous actin
ISS
GO_REF:0000024 		ACCEPT
Summary: filamentous actin: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0035374 chondroitin sulfate binding
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: chondroitin sulfate binding: a specific molecular interaction consistent with DPYSL3's cytoskeletal-adapter role.
Reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function. Non-core.
GO:0044297 cell body
ISS
GO_REF:0000024 		ACCEPT
Summary: cell body: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).
Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
GO:0048678 response to axon injury
ISS
GO_REF:0000024 		ACCEPT
Summary: response to axon injury: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0051017 actin filament bundle assembly
ISS
GO_REF:0000024 		ACCEPT
Summary: actin filament bundle assembly: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0051491 positive regulation of filopodium assembly
ISS
GO_REF:0000024 		ACCEPT
Summary: positive regulation of filopodium assembly: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0051764 actin crosslink formation
ISS
GO_REF:0000024 		ACCEPT
Summary: actin crosslink formation: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development).
Reason: Core biological process for a CRMP-family cytoskeletal regulator.
GO:0070382 exocytic vesicle
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: exocytic vesicle: a secondary/broad or context-specific localization for DPYSL3.
Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
GO:0071345 cellular response to cytokine stimulus
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: cellular response to cytokine stimulus: a broader/secondary process for DPYSL3.
Reason: Valid but non-core relative to the cytoskeletal-regulation function.

Core Functions

Catalytically inactive CRMP-family actin-/cytoskeleton-regulating protein that binds and bundles F-actin, regulates filopodia and neuron projection development during semaphorin signaling.

Molecular Function:
filamin binding
Directly Involved In:
actin crosslink formation neuron development
Cellular Locations:
cytosol growth cone
Supporting Evidence:
  • file:human/DPYSL3/DPYSL3-uniprot.txt
    Lacks most of the conserved residues that are essential for

References

GO_REF:0000002
GO annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified annotations to orthologs by curator judgment
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
GO annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
GO_REF:0000052
GO annotation based on curation of immunofluorescence data (HPA)
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
file:human/DPYSL3/DPYSL3-uniprot.txt
UniProt entry for DPYSL3
  • DPYSL3 lacks the metal-cofactor-binding residues required for dihydropyrimidinase activity.
    "Lacks most of the conserved residues that are essential for"
  • DPYSL3 belongs to the metallo-dependent hydrolase superfamily.
    "Belongs to the metallo-dependent hydrolases superfamily."
PMID:21044950
Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:29892012
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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)

Suggested Questions for Experts

Q: How does CRMP4 (DPYSL3) coordinate F-actin bundling and filopodium dynamics, and is this actin role separable from the microtubule functions of its paralog CRMP2?

Suggested Experiments

Experiment: Assay F-actin bundling and filopodium formation with wild-type vs actin-binding-deficient DPYSL3 in neurons, comparing to DPYSL2.

Hypothesis: DPYSL3 acts primarily through F-actin bundling rather than microtubules.

📄 View Raw YAML

 
# yaml-language-server: $schema=../../../src/ai_gene_review/schema/gene_review.yaml
id: Q14195
gene_symbol: DPYSL3
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Dihydropyrimidinase-related protein 3 (DPYSL3/CRMP4), a cytoplasmic CRMP-family protein required
  for class-3 semaphorin signaling and cytoskeletal remodeling. A catalytically dead member of the metallo-dependent
  hydrolase (dihydropyrimidinase) superfamily, it lacks the conserved metal-cofactor residues and has
  no dihydropyrimidinase activity. DPYSL3 is distinguished by F-actin binding/bundling and filopodium
  regulation, binds filamin and chondroitin sulfate, and modulates neuron projection development, growth-cone
  dynamics and cell migration. It forms homo- and hetero-tetramers with other CRMPs.
alternative_products:
- name: '1'
  id: Q14195-1
- name: LCRMP-4
  id: Q14195-2
  sequence_note: VSP_042546
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 DPYSL3 (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: DPYSL3 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/DPYSL3/DPYSL3-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). DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
    - reference_id: file:human/DPYSL3/DPYSL3-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: DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
- term:
    id: GO:0051764
    label: actin crosslink formation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'actin crosslink formation: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3
      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:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: 'cytoplasm: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- 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).
      DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
    - reference_id: file:human/DPYSL3/DPYSL3-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). DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
      supporting_text: Lacks most of the conserved residues that are essential for
    - reference_id: file:human/DPYSL3/DPYSL3-uniprot.txt
      supporting_text: Belongs to the metallo-dependent hydrolases superfamily.
- term:
    id: GO:0030426
    label: growth cone
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: 'growth cone: a core subcellular location for DPYSL3 (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:21044950
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:21044950); supports DPYSL3'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: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: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:25416956
  qualifier: enables
  isoform: Q14195-2
  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:32296183
  qualifier: enables
  isoform: Q14195-2
  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:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'extracellular region: a secondary/broad or context-specific localization for DPYSL3.'
    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: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0010976
    label: positive regulation of neuron projection development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'positive regulation of neuron projection development: a core neuronal/cytoskeletal process
      for the CRMP family (DPYSL3 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:0010977
    label: negative regulation of neuron projection development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'negative regulation of neuron projection development: a core neuronal/cytoskeletal process
      for the CRMP family (DPYSL3 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:0017124
    label: SH3 domain binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: 'SH3 domain binding: a specific molecular interaction consistent with DPYSL3''s cytoskeletal-adapter
      role.'
    action: KEEP_AS_NON_CORE
    reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function.
      Non-core.
- term:
    id: GO:0030027
    label: lamellipodium
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'lamellipodium: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0030336
    label: negative regulation of cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'negative regulation of cell migration: a core neuronal/cytoskeletal process for the CRMP
      family (DPYSL3 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:0031941
    label: filamentous actin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: 'filamentous actin: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0035374
    label: chondroitin sulfate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: 'chondroitin sulfate binding: a specific molecular interaction consistent with DPYSL3''s
      cytoskeletal-adapter role.'
    action: KEEP_AS_NON_CORE
    reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function.
      Non-core.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: 'Identical protein binding: DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
      supporting_text: Homotetramer
- term:
    id: GO:0044297
    label: cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'cell body: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: 'synapse: a secondary/broad or context-specific localization for DPYSL3.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0048666
    label: neuron development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'neuron development: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3 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:0051017
    label: actin filament bundle assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'actin filament bundle assembly: a core neuronal/cytoskeletal process for the CRMP family
      (DPYSL3 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:0051219
    label: phosphoprotein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: 'phosphoprotein binding: a specific molecular interaction consistent with DPYSL3''s cytoskeletal-adapter
      role.'
    action: KEEP_AS_NON_CORE
    reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function.
      Non-core.
- term:
    id: GO:0051491
    label: positive regulation of filopodium assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'positive regulation of filopodium assembly: a core neuronal/cytoskeletal process for the
      CRMP family (DPYSL3 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:0051764
    label: actin crosslink formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'actin crosslink formation: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3
      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:0070382
    label: exocytic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'exocytic vesicle: a secondary/broad or context-specific localization for DPYSL3.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: 'Identical protein binding: DPYSL3 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/DPYSL3/DPYSL3-uniprot.txt
      supporting_text: Homotetramer
- term:
    id: GO:0031005
    label: filamin binding
  evidence_type: IPI
  original_reference_id: PMID:25358863
  qualifier: enables
  review:
    summary: 'filamin binding: a specific molecular interaction consistent with DPYSL3''s cytoskeletal-adapter
      role.'
    action: ACCEPT
    reason: Filamin binding is a specific, experimentally demonstrated interaction (PMID:25358863) central
      to this CRMP's cytoskeletal-adapter role; retained as the representative core binding molecular
      function.
- 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 DPYSL3 (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 DPYSL3 (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 DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'extracellular region: a secondary/broad or context-specific localization for DPYSL3.'
    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: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0010976
    label: positive regulation of neuron projection development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'positive regulation of neuron projection development: a core neuronal/cytoskeletal process
      for the CRMP family (DPYSL3 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:0010977
    label: negative regulation of neuron projection development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'negative regulation of neuron projection development: a core neuronal/cytoskeletal process
      for the CRMP family (DPYSL3 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:0017124
    label: SH3 domain binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: 'SH3 domain binding: a specific molecular interaction consistent with DPYSL3''s cytoskeletal-adapter
      role.'
    action: KEEP_AS_NON_CORE
    reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function.
      Non-core.
- term:
    id: GO:0030027
    label: lamellipodium
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'lamellipodium: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0030336
    label: negative regulation of cell migration
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'negative regulation of cell migration: a core neuronal/cytoskeletal process for the CRMP
      family (DPYSL3 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:0030426
    label: growth cone
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'growth cone: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0031941
    label: filamentous actin
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    summary: 'filamentous actin: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0035374
    label: chondroitin sulfate binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: 'chondroitin sulfate binding: a specific molecular interaction consistent with DPYSL3''s
      cytoskeletal-adapter role.'
    action: KEEP_AS_NON_CORE
    reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function.
      Non-core.
- term:
    id: GO:0044297
    label: cell body
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'cell body: a core subcellular location for DPYSL3 (cytoplasmic/cytoskeletal CRMP).'
    action: ACCEPT
    reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein.
- term:
    id: GO:0048678
    label: response to axon injury
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'response to axon injury: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3
      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:0051017
    label: actin filament bundle assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'actin filament bundle assembly: a core neuronal/cytoskeletal process for the CRMP family
      (DPYSL3 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:0051491
    label: positive regulation of filopodium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'positive regulation of filopodium assembly: a core neuronal/cytoskeletal process for the
      CRMP family (DPYSL3 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:0051764
    label: actin crosslink formation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'actin crosslink formation: a core neuronal/cytoskeletal process for the CRMP family (DPYSL3
      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:0070382
    label: exocytic vesicle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: colocalizes_with
  review:
    summary: 'exocytic vesicle: a secondary/broad or context-specific localization for DPYSL3.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics).
- term:
    id: GO:0071345
    label: cellular response to cytokine stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'cellular response to cytokine stimulus: a broader/secondary process for DPYSL3.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core relative to the cytoskeletal-regulation function.
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/DPYSL3/DPYSL3-uniprot.txt
  title: UniProt entry for DPYSL3
  findings:
  - statement: DPYSL3 lacks the metal-cofactor-binding residues required for dihydropyrimidinase activity.
    supporting_text: Lacks most of the conserved residues that are essential for
  - statement: DPYSL3 belongs to the metallo-dependent hydrolase superfamily.
    supporting_text: Belongs to the metallo-dependent hydrolases superfamily.
- id: PMID:21044950
  title: Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling
    in human cells.
  findings: []
- id: PMID:25358863
  title: Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling.
  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:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  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: []
aliases:
- CRMP4
- CRMP-4
- DRP-3
- ULIP-1
- Collapsin response mediator protein 4
core_functions:
- description: Catalytically inactive CRMP-family actin-/cytoskeleton-regulating protein that binds and
    bundles F-actin, regulates filopodia and neuron projection development during semaphorin signaling.
  directly_involved_in:
  - id: GO:0051764
    label: actin crosslink formation
  - id: GO:0048666
    label: neuron development
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0030426
    label: growth cone
  supported_by:
  - reference_id: file:human/DPYSL3/DPYSL3-uniprot.txt
    supporting_text: Lacks most of the conserved residues that are essential for
  molecular_function:
    id: GO:0031005
    label: filamin binding
suggested_questions:
- question: How does CRMP4 (DPYSL3) coordinate F-actin bundling and filopodium dynamics, and is this actin
    role separable from the microtubule functions of its paralog CRMP2?
suggested_experiments:
- hypothesis: DPYSL3 acts primarily through F-actin bundling rather than microtubules.
  description: Assay F-actin bundling and filopodium formation with wild-type vs actin-binding-deficient
    DPYSL3 in neurons, comparing to DPYSL2.