Dihydropyrimidinase-related protein 1 (CRMP1/DPYSL1), a cytoplasmic CRMP-family protein required for class-3 semaphorin (Sema3A) signaling and growth-cone collapse during neuronal development. A pseudoenzyme with respect to the ancestral dihydropyrimidinase reaction, it lacks the conserved metal-cofactor residues and has no dihydropyrimidinase activity. CRMP1 regulates neuron projection development and dendritic/synaptic organization, binds filamin, and forms homo- and hetero-tetramers with other CRMPs; it also has reported roles in cell migration and as an invasion suppressor.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: cytosol: a core subcellular location for CRMP1 (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: The curated NOT assertion for CRMP1 concerns pyrimidine nucleobase catabolism specifically. Reason: Retain the curated phylogenetic negation for the ancestral pyrimidine-degradation pathway, consistent with loss of its dihydropyrimidinase reaction and the characterized cytoskeletal role. No alternative structural or cofactor contribution to pyrimidine catabolism was identified. This does not imply exclusion from all nucleic-acid metabolism or from processes performed noncatalytically. Supporting Evidence: file:human/CRMP1/CRMP1-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: CRMP1 lacks the conserved catalytic apparatus for ancestral dihydropyrimidinase-type cyclic-amide hydrolysis. Reason: The target UniProt caution documents missing metal-cofactor ligands; the CRMP2 crystal structure and CRMP5 negative assay independently corroborate loss of this ancestral reaction in the CRMP subfamily. The OpenScientist report supplies residue-level comparisons, with direct-assay and paralog-inference limitations kept explicit. These data challenge retention of catalytic activity in this target, rather than the strength or number of phylogenetic donors. Propagation Review Root cause: PROPAGATION BAD Failure modes: PSEUDO OR SUBACTIVITY LOSS Sources checked: PANTHER:PTN000182670 SUPPORTS SOURCE BUT NOT TARGET Proximate IBA ancestral node verified in the cached GOA WITH/FROM field. Target-specific loss of the catalytic apparatus, documented in the cited primary/sequence evidence, challenges retention of this ancestral reaction. The full PAINT reconstruction was not independently repeated; extant donor count or target self-inclusion is not evidence against the annotation. Supporting Evidence: file:human/CRMP1/CRMP1-uniprot.txt Lacks most of the conserved residues that are essential for PMID:28044206 Although CRMP-2, and other CRMPs, belong to the dihydropyrimidinase family, they have lost the enzymatic active site. PMID:23373749 CRMP-5 does not have any detectable amidohydrolase activity. file:human/CRMP1/CRMP1-hypotheses/function-hypothesis-go-0016812/openscientist.md CRMP1 is a cytoplasmic signaling adapter protein that functions through **protein-protein interactions**, not enzymatic catalysis. |
| GO:0004157 dihydropyrimidinase activity | IBA NOT GO_REF:0000033 | ACCEPT | Summary: NOT: CRMP1 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/CRMP1/CRMP1-uniprot.txt Lacks most of the conserved residues that are essential for |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: cytoplasm: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: centrosome: a secondary/broad or context-specific localization for CRMP1. Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics). |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: spindle: a secondary/broad or context-specific localization for CRMP1. Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics). |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: cytoskeleton: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | REMOVE | Summary: The broad catalytic mapping derives from a hydrolase domain whose ancestral active site has been lost. Reason: For this target the mapped InterPro hydrolase reaction is contradicted by loss of the dihydropyrimidinase metal center, and the reviewed evidence does not establish an alternative hydrolytic reaction. Remove this catalytic inference rather than generalizing a defunct enzyme activity. This is not a claim that all CRMP paralogs can never evolve another enzymatic activity. Supporting Evidence: file:human/CRMP1/CRMP1-uniprot.txt Lacks most of the conserved residues that are essential for PMID:28044206 Although CRMP-2, and other CRMPs, belong to the dihydropyrimidinase family, they have lost the enzymatic active site. PMID:23373749 CRMP-5 does not have any detectable amidohydrolase activity. |
| GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds | IEA GO_REF:0000002 | REMOVE | Summary: The broad catalytic mapping derives from a hydrolase domain whose ancestral active site has been lost. Reason: For this target the mapped InterPro hydrolase reaction is contradicted by loss of the dihydropyrimidinase metal center, and the reviewed evidence does not establish an alternative hydrolytic reaction. Remove this catalytic inference rather than generalizing a defunct enzyme activity. This is not a claim that all CRMP paralogs can never evolve another enzymatic activity. Supporting Evidence: file:human/CRMP1/CRMP1-uniprot.txt Lacks most of the conserved residues that are essential for PMID:28044206 Although CRMP-2, and other CRMPs, belong to the dihydropyrimidinase family, they have lost the enzymatic active site. PMID:23373749 CRMP-5 does not have any detectable amidohydrolase activity. |
| GO:0030426 growth cone | IEA GO_REF:0000120 | ACCEPT | Summary: growth cone: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | ACCEPT | Summary: The neuronal cell body is a supported location of CRMP1. Reason: Perikaryon denotes the neuronal soma and is consistent with the independently retained neuronal-cell-body and cytoplasmic annotations. This location is part of the protein's core neuronal distribution; broadness alone is not a reason to demote it. Supporting Evidence: file:human/CRMP1/CRMP1-uniprot.txt Perikaryon |
| GO:0005515 protein binding | IPI PMID:15383276 A protein interaction network links GIT1, an enhancer of hun... | REMOVE | Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function. Reason: PMID:15383276 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone. |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | REMOVE | Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function. Reason: PMID:16169070 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | REMOVE | Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function. Reason: PMID:21900206 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone. |
| GO:0005515 protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | REMOVE | Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function. Reason: PMID:24722188 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function. Reason: PMID:25416956 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function. Reason: PMID:32296183 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: The cited interaction evidence is retained as context, but the generic protein-binding term does not specify a molecular function. Reason: PMID:32814053 reports protein interactions. Remove this uninformative GO:0005515 assertion under the annotation-reviewer policy; this does not reject the interaction or infer that the experiment assayed the wrong gene. A specific molecular function is not inferred from an interaction screen alone. |
| GO:0042802 identical protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | ACCEPT | Summary: Homomeric association is an established structural property of CRMP assemblies. Reason: CRMPs form homo- and heterotetramers, and oligomeric assembly is part of their core cytoskeletal signaling architecture. Identical protein binding specifies self-association and is not equivalent to uninformative generic protein binding. Retain the supported annotation without claiming that every tetramer is constitutively stable. Supporting Evidence: PMID:23373749 CRMPs exist as homo- and/or hetero-tetramers in vivo and participate in signaling transduction, cytoskeleton rearrangements, and endocytosis. |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: Homomeric association is an established structural property of CRMP assemblies. Reason: CRMPs form homo- and heterotetramers, and oligomeric assembly is part of their core cytoskeletal signaling architecture. Identical protein binding specifies self-association and is not equivalent to uninformative generic protein binding. Retain the supported annotation without claiming that every tetramer is constitutively stable. Supporting Evidence: PMID:23373749 CRMPs exist as homo- and/or hetero-tetramers in vivo and participate in signaling transduction, cytoskeleton rearrangements, and endocytosis. |
| GO:0015629 actin cytoskeleton | IEA GO_REF:0000107 | ACCEPT | Summary: actin cytoskeleton: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0030425 dendrite | IEA GO_REF:0000107 | ACCEPT | Summary: dendrite: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | ACCEPT | Summary: neuronal cell body: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0051219 phosphoprotein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: phosphoprotein binding: a specific molecular interaction consistent with CRMP1's cytoskeletal-adapter role. Reason: Real, specific binding; informative but secondary to the core cytoskeletal-regulation function. Non-core. |
| GO:0071526 semaphorin-plexin signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: semaphorin-plexin signaling pathway: a core neuronal/cytoskeletal process for the CRMP family (CRMP1 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development). Reason: Core biological process for a CRMP-family cytoskeletal regulator. Supporting Evidence: file:human/CRMP1/CRMP1-uniprot.txt semaphorin |
| GO:0098793 presynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: presynapse: a secondary/broad or context-specific localization for CRMP1. Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics). |
| GO:0098794 postsynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: postsynapse: a secondary/broad or context-specific localization for CRMP1. Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics). |
| GO:0150052 regulation of postsynapse assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of postsynapse assembly (IEA, ortholog transfer): a peripheral, electronically inferred role, not an established core CRMP1 function. Reason: Retain this conserved postsynaptic assembly role as a specialized neuronal context relative to the representative semaphorin/cytoskeletal function. Ortholog transfer does not require a separate human experiment, and the absence of one is not a biological refutation. |
| GO:0005813 centrosome | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: centrosome: a secondary/broad or context-specific localization for CRMP1. Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics). |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: cytosol: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0005737 cytoplasm | EXP PMID:11562390 Collapsin response mediator protein-1 and the invasion and m... | ACCEPT | Summary: cytoplasm: a core subcellular location for CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | ACCEPT | Summary: The neuronal cell body is a supported location of CRMP1. Reason: Perikaryon denotes the neuronal soma and is consistent with the independently retained neuronal-cell-body and cytoplasmic annotations. This location is part of the protein's core neuronal distribution; broadness alone is not a reason to demote it. Supporting Evidence: file:human/CRMP1/CRMP1-uniprot.txt Perikaryon |
| GO:0030496 midbody | IDA PMID:19799413 From midbody protein-protein interaction network constructio... | KEEP AS NON CORE | Summary: midbody: a secondary/broad or context-specific localization for CRMP1. Reason: Plausible but non-core (broad term, division-/synapse-specific, or high-throughput proteomics). |
| GO:0010977 negative regulation of neuron projection development | IGI PMID:25358863 Amino- and carboxyl-terminal domains of Filamin-A interact w... | ACCEPT | Summary: negative regulation of neuron projection development: a core neuronal/cytoskeletal process for the CRMP family (CRMP1 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development). Reason: Core biological process for a CRMP-family cytoskeletal regulator. |
| 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 CRMP1'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 CRMP1 (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 CRMP1 (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 CRMP1 (cytoplasmic/cytoskeletal CRMP). Reason: Correct core localization for a cytoskeleton-associated cytoplasmic protein. |
| GO:0006139 nucleobase-containing compound metabolic process | TAS PMID:8973361 A novel gene family defined by human dihydropyrimidinase and... | UNDECIDED | Summary: The legacy broad metabolic-process assertion cannot be judged solely from loss of dihydropyrimidinase catalysis. Reason: PMID:8973361 is available here only as an abstract documenting cloning, homology and expression. GO:0006139 covers metabolism of nucleobases, nucleotides and nucleic acids; loss of one hydrolytic reaction does not exclude noncatalytic participation in that broad process. A relevant metabolic role is not established by the accessible material, but absence of the original full text prevents a confident source-level rejection. Keep the specific catalytic rejection separate. Supporting Evidence: PMID:8973361 We have isolated cDNA clones encoding dihydropyrimidinase (DHPase) from human liver and its three homologues from human fetal brain. |
| 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 (CRMP1 acts in semaphorin-driven cytoskeleton remodeling and neurite/axon development). Reason: Core biological process for a CRMP-family cytoskeletal regulator. |
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Download this section (compressed HTML)Q: By what mechanism does CRMP1 mediate Sema3A-induced growth-cone collapse, and how does this relate to its reported invasion-suppressor activity in cancer?
Experiment: Compare Sema3A-induced growth-cone collapse and tumour-cell invasion in cells expressing wild-type vs signaling-deficient CRMP1.
Hypothesis: CRMP1's Sema3A growth-cone-collapse function underlies its invasion-suppressor activity.
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