Amino acid sequence conservation of the algesic fragment of myelin basic protein is required for its interaction with CDK5 and function in pain.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30079618", "kind": "science-record", "revision": 5, "content_hash": "sha256:cba778d53ede3e48bd636e0b25dd734d814688c1901b0534795523aa9dc32924", "created_at": "2026-11-01T15:40:36Z", "updated_at": "2026-11-01T18:49:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Amino acid sequence conservation of the algesic fragment of myelin basic protein is required for its interaction with CDK5 and function in pain.", "doi": "10.1111/febs.14623", "pmid": "30079618", "authors": ["Andrei V Chernov", "Albert G Remacle", "Swathi K Hullugundi", "Piotr Cieplak", "Mila Angert", "Jennifer Dolkas", "Veronica I Shubayev", "Alex Y Strongin"], "journal": "The FEBS journal", "year": 2018, "abstract": "Neurotrauma frequently results in neuropathic pain. Our earlier studies revealed that peripheral neurotrauma-induced fragmentation of the myelin basic protein (MBP), a major component of the myelin sheath formed by Schwann cells, initiates a pain response from light touch stimuli (mechanical allodynia) in rodents. Here, we identified the cyclin-dependent kinase 5 (CDK5), as an intracellular interactor of MBP in Schwann cells. The algesic peptide fragment of MBP directly associated with CDK5. When complexed with its p25 coactivator, CDK5 phosphorylated the conserved MBP sequence. The expressed MBP fragment colocalized with CDK5 in Schwann cell protrusions. Roscovitine, an ATP-competitive CDK5 inhibitor, disrupted localization of the expressed MBP peptide. Mutations in the evolutionary conserved MBP algesic sequence resulted in the interference with intracellular trafficking of the MBP fragment and kinase activity of CDK5 and diminished pain-like behavior in rodents. Our findings show that MBP fragment amino acid sequence conservation determines its interactions, trafficking, and pronociceptive activity. Because CDK5 activity controls both neurogenesis and nociception, the algesic MBP fragment may be involved in the regulation of the CDK5 functionality in pain signaling and postinjury neurogenesis in vertebrates.\nDATABASE: The novel RNA-seq datasets were deposited in the GEO database under the accession number GSE107020.", "claims": [{"id": "claim-target-result", "statement": "The algesic MBP fragment directly binds and is phosphorylated by CDK5, while sequence mutations impair trafficking, kinase activity, and pain-like behavior; statistical analysis used repeated-measures ANOVA with Bonferroni post-hoc testing (p≤0.05), and the RNA-seq source data are available in GEO under accession GSE107020.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:30079618", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Mutations in the evolutionary conserved MBP algesic sequence resulted in the interference with intracellular trafficking of the MBP fragment and kinase activity of CDK5 and diminished pain-like behavior in rodents."}, {"asset": "source:pmid:30079618", "locator": "sections[30] \"Data analyses\" paragraph 2", "quote": "Statistical analyses were performed using GraphPad Prism (GraphPad Software) by analyses of variance (ANOVA) for repeated measures, followed by the Bonferroni post-hoc test, unless specified otherwise. p≤0.05 values were considered significant."}, {"asset": "source:pmid:30079618", "locator": "sections[33] \"fn-group\" paragraph 1", "quote": "The novel RNA-seq datasets were deposited in the GEO database under the accession number GSE107020."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The algesic MBP fragment directly binds and is phosphorylated by CDK5, while sequence mutations impair trafficking, kinase activity, and pain-like behavior; statistical analysis used repeated-measures ANOVA with Bonferroni post-hoc testing (p≤0.05), and the RNA-seq source data are available in GEO under accession GSE107020.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30079618"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30079618", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/febs.14623", "sha256": "sha256:b7bcd1218265df91b2fd2f79215f8f928d2f67a4d1c7a93d2221aee807e0238e", "bytes": 44404, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1111/febs.14623", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6288010", "source": "ncbi_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "absent", "methods": [], "targets": [], "gaps": ["method", "operations"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (not named), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": [], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:30079618"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:35:20Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 2, "usage": {"prompt_tokens": 22733, "completion_tokens": 876, "cached_tokens": 520}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:30079618", "type": "paper", "label": "pmid:30079618"}, {"id": "source:pmid:30079618", "type": "manuscript", "label": "PMID 30079618 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30079618", "type": "paper", "label": "pmid:30079618"}, {"id": "source:pmid:30079618", "type": "manuscript", "label": "PMID 30079618 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30079618", "type": "extraction", "used": ["source:pmid:30079618"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:30079618", "parent_hash": "sha256:0e0dd99faacbdf780fd10667f8aa7370a622c240c5c30877c75c8e0d2da4dc54", "fork_of": null, "generation": 4}, "gaps": ["execution.not_run", "method", "operations", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ogenesis in vertebrates. DATABASE: The novel RNA-seq datasets were deposited in the GEO database"], "order_basis": "paper_text_order:1453", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.834, "evidence": ["nerves of postnatal (day 1-3) Sprague-Dawley rats [62]. Cells were purified from fibroblasts u", "5% CO2. Animal models Female Sprague-Dawley rats (8-10 weeks old, 200-225 g) were obtained fr"], "order_basis": "paper_text_order:1672", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["re collected for the quantitative RT-PCR and immunostaining analyses. Tissues from naïve animals were us"], "order_basis": "paper_text_order:3051", "id": "assay:3"}]}