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.
| 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.
|
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?
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.
# 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.