{"gene":"CLIP2","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":1997,"finding":"CLIP-115 (encoded by CLIP2) was identified as a novel brain-specific cytoplasmic linker protein that contains two N-terminal microtubule-binding domains and a long coiled-coil region. Direct experiments showed CLIP-115 binds microtubules and is enriched in dendritic lamellar bodies (DLBs); local microtubule depolymerization led to a temporary reduction of DLBs, establishing a role for CLIP-115 in brain-specific organelle translocation.","method":"cDNA cloning, subcellular fractionation, immunolocalization, microtubule depolymerization experiments in neurons","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — original characterization with multiple orthogonal methods (biochemistry, live imaging, functional perturbation) in a single foundational study","pmids":["9427243"],"is_preprint":false},{"year":2000,"finding":"Efficient microtubule binding by CLIP-115 requires not only the conserved microtubule-binding (MTB) domains but also the flanking basic, serine-rich regions; phosphorylation negatively regulates microtubule binding. CLIP-115 accumulates at distal ends of growing microtubules in transfected COS-1 cells, co-localizing with CLIP-170. CLIP-115 forms homodimers linked by disulfide bridges in vitro, and Cys391 specifically controls microtubule bundling capacity of certain mutants.","method":"Transfection of deletion/point mutants in COS-1 cells, microtubule co-sedimentation assays, in vitro phosphorylation, live-cell imaging, in vitro disulfide cross-linking","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal biochemical and cell biological methods including mutagenesis and in vitro reconstitution in a single study","pmids":["10825300"],"is_preprint":false},{"year":2001,"finding":"CLIP-115 and CLIP-170 associate with two CLIP-associated proteins (CLASPs), homologues of Drosophila Orbit/Mast. CLASPs bind CLIPs and microtubules, co-localize with CLIPs at microtubule distal ends, and have microtubule-stabilizing effects. After serum induction, CLASPs relocalize to distal microtubule segments at the leading edge in a PI3-kinase- and GSK-3β-dependent manner. Antibody injection showed CLASP2 is required for orientation of stabilized microtubules toward the leading edge.","method":"Yeast two-hybrid, co-immunoprecipitation, transfection/overexpression in fibroblasts, antibody microinjection, immunofluorescence microscopy","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP and functional rescue experiments with antibody injection across multiple orthogonal approaches; highly cited foundational study","pmids":["11290329"],"is_preprint":false},{"year":2004,"finding":"CLIP-115 and CLIP-170 are discussed in the context of Williams Syndrome (WBS): knockout mice lacking CLIP-115 show distinct neurological and behavioral phenotypes, consistent with a role for CLIP-115 in the cytoskeletal regulation underlying the neurological symptoms of WBS. The review places CLIP-115 function downstream of microtubule network regulation in a developmental neurological context.","method":"Knockout mouse phenotyping (neurological and behavioral analysis) reviewed","journal":"BioEssays","confidence":"Medium","confidence_rationale":"Tier 2 — KO mouse with defined neurological phenotype, but review paper summarizing prior findings","pmids":["14745832"],"is_preprint":false},{"year":2012,"finding":"Genetic analysis of two healthy siblings with a pure hemizygous deletion of CLIP2 showed no physical or cognitive features of Williams-Beuren syndrome and average IQ without the WBS cognitive profile, demonstrating that CLIP2 haploinsufficiency alone is not sufficient to produce the WBS phenotype or cognitive profile, thus distinguishing CLIP2's contribution from that of GTF2IRD1 and GTF2I.","method":"Genomic deletion mapping (array CGH), cognitive testing (IQ assessment) in human patients with isolated CLIP2 hemizygous deletion","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 — human genetic loss-of-function with defined cognitive phenotype assessment, but single family/small cohort","pmids":["22608712"],"is_preprint":false}],"current_model":"CLIP2 (CLIP-115) is a brain-enriched cytoplasmic linker protein that tracks growing microtubule plus ends via two N-terminal microtubule-binding domains (assisted by flanking basic/serine-rich regions) and a homodimerizing coiled-coil; it localizes to dendritic lamellar bodies and controls their distribution through microtubule association, interacts with CLASP proteins to stabilize microtubules at the cell leading edge in a PI3K/GSK-3β-regulated manner, and its phosphorylation state regulates microtubule binding affinity, while loss-of-function studies in mice reveal neurological and behavioral deficits, though human haploinsufficiency alone does not recapitulate the Williams-Beuren syndrome cognitive profile."},"narrative":{"teleology":[{"year":1997,"claim":"Establishing that CLIP2 is a brain-specific microtubule-binding protein linked to organelle positioning resolved its molecular identity and provided the first functional context — localizing to dendritic lamellar bodies whose distribution depends on intact microtubules.","evidence":"cDNA cloning, subcellular fractionation, immunolocalization, and microtubule depolymerization experiments in neurons","pmids":["9427243"],"confidence":"High","gaps":["Structural basis for microtubule-binding domain selectivity was unresolved","Regulatory signals controlling CLIP-115 activity were unknown","In vivo loss-of-function phenotype had not been determined"]},{"year":2000,"claim":"Dissecting the domain requirements for microtubule binding showed that flanking basic/serine-rich regions are necessary beyond the conserved MTB domains, that phosphorylation inhibits binding, and that CLIP-115 homodimerizes via disulfide bridges — establishing key regulatory and structural principles.","evidence":"Deletion/point mutant transfection in COS-1 cells, microtubule co-sedimentation, in vitro phosphorylation, and disulfide cross-linking","pmids":["10825300"],"confidence":"High","gaps":["Identity of the kinase(s) responsible for regulatory phosphorylation was unknown","Functional significance of CLIP-115/CLIP-170 co-localization at plus ends remained unresolved","Whether dimerization is required for in vivo function was untested"]},{"year":2001,"claim":"Identifying CLASPs as CLIP-115/CLIP-170 interactors that stabilize microtubules at the leading edge downstream of PI3K and GSK-3β placed CLIP2 within a signaling-regulated plus-end complex controlling cell polarity.","evidence":"Yeast two-hybrid, co-immunoprecipitation, overexpression in fibroblasts, and antibody microinjection","pmids":["11290329"],"confidence":"High","gaps":["Whether the CLIP-115–CLASP interaction is direct or bridged was not fully resolved","Relative contributions of CLIP-115 versus CLIP-170 in recruiting CLASPs were unclear","Neuronal relevance of the PI3K/GSK-3β–CLASP–CLIP axis was not tested"]},{"year":2004,"claim":"Demonstrating that CLIP-115 knockout mice display neurological and behavioral deficits established that the protein's microtubule-regulatory function is essential for normal brain development and behavior.","evidence":"Knockout mouse phenotyping with neurological and behavioral analysis (reviewed)","pmids":["14745832"],"confidence":"Medium","gaps":["Primary data were presented in a review context; detailed mechanistic dissection of neuronal deficits was lacking","Which neuronal cell types or circuits are most affected was unresolved","Relationship between microtubule dynamics defects and behavioral outcomes was correlative"]},{"year":2012,"claim":"Showing that isolated human CLIP2 haploinsufficiency does not produce the Williams-Beuren syndrome cognitive profile distinguished CLIP2's contribution from that of GTF2IRD1/GTF2I and refined the genotype–phenotype map of the WBS deletion region.","evidence":"Array CGH deletion mapping and cognitive testing in siblings with pure CLIP2 hemizygous deletion","pmids":["22608712"],"confidence":"Medium","gaps":["Only a single family was studied, limiting generalizability","Subtle neurological phenotypes below the resolution of standard cognitive testing could be missed","Whether CLIP2 loss interacts epistatically with other WBS-region gene deletions was not tested"]},{"year":null,"claim":"The in vivo kinase(s) regulating CLIP2 phosphorylation, the structural basis for its selective plus-end tracking, and the specific neuronal circuits and developmental processes disrupted by CLIP2 loss remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No kinase or phosphatase acting on CLIP2 has been identified in vivo","No high-resolution structure of CLIP2 microtubule-binding domains exists","The neuronal cell-type-specific functions of CLIP2 are undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,2]}],"complexes":[],"partners":["CLIP1","CLASP1","CLASP2"],"other_free_text":[]},"mechanistic_narrative":"CLIP2 (CLIP-115) is a brain-enriched cytoplasmic linker protein that tracks growing microtubule plus ends via two N-terminal microtubule-binding domains flanked by basic/serine-rich regions required for efficient microtubule association, and forms homodimers through its coiled-coil domain linked by disulfide bridges [PMID:9427243, PMID:10825300]. Phosphorylation negatively regulates its microtubule-binding affinity, and it co-localizes with CLIP-170 at microtubule distal ends; CLIP2 interacts with CLASP proteins that stabilize microtubules at the cell leading edge in a PI3K/GSK-3β-dependent manner [PMID:10825300, PMID:11290329]. In neurons, CLIP2 localizes to dendritic lamellar bodies and controls their distribution through microtubule association; knockout mice lacking CLIP2 exhibit neurological and behavioral deficits, though isolated CLIP2 haploinsufficiency in humans does not recapitulate the Williams-Beuren syndrome cognitive profile [PMID:9427243, PMID:14745832, PMID:22608712]."},"prefetch_data":{"uniprot":{"accession":"Q9UDT6","full_name":"CAP-Gly domain-containing linker protein 2","aliases":["Cytoplasmic linker protein 115","CLIP-115","Cytoplasmic linker protein 2","Williams-Beuren syndrome chromosomal region 3 protein","Williams-Beuren syndrome chromosomal region 4 protein"],"length_aa":1046,"mass_kda":115.8,"function":"Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations (By similarity)","subcellular_location":"Cytoplasm; Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q9UDT6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CLIP2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CLIP2","total_profiled":1310},"omim":[{"mim_id":"606821","title":"COMPONENT OF OLIGOMERIC GOLGI COMPLEX 5; COG5","url":"https://www.omim.org/entry/606821"},{"mim_id":"603432","title":"CAP-GLY DOMAIN-CONTAINING LINKER PROTEIN 2; CLIP2","url":"https://www.omim.org/entry/603432"},{"mim_id":"194050","title":"WILLIAMS-BEUREN SYNDROME; WBS","url":"https://www.omim.org/entry/194050"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"brain","ntpm":78.2}],"url":"https://www.proteinatlas.org/search/CLIP2"},"hgnc":{"alias_symbol":["CLIP-115","KIAA0291","WSCR4","CLIP","WSCR3"],"prev_symbol":["WBSCR4","CYLN2","WBSCR3"]},"alphafold":{"accession":"Q9UDT6","domains":[{"cath_id":"2.30.30.190","chopping":"84-147","consensus_level":"high","plddt":93.3219,"start":84,"end":147},{"cath_id":"2.30.30.190","chopping":"224-288","consensus_level":"high","plddt":90.4248,"start":224,"end":288}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UDT6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UDT6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UDT6-F1-predicted_aligned_error_v6.png","plddt_mean":73.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CLIP2","jax_strain_url":"https://www.jax.org/strain/search?query=CLIP2"},"sequence":{"accession":"Q9UDT6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UDT6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UDT6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UDT6"}},"corpus_meta":[{"pmid":"20371350","id":"PMC_20371350","title":"Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.","date":"2010","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/20371350","citation_count":2303,"is_preprint":false},{"pmid":"19536157","id":"PMC_19536157","title":"Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps.","date":"2009","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/19536157","citation_count":1440,"is_preprint":false},{"pmid":"18978773","id":"PMC_18978773","title":"HITS-CLIP yields genome-wide insights into brain alternative RNA processing.","date":"2008","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/18978773","citation_count":1090,"is_preprint":false},{"pmid":"27018577","id":"PMC_27018577","title":"Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).","date":"2016","source":"Nature methods","url":"https://pubmed.ncbi.nlm.nih.gov/27018577","citation_count":1054,"is_preprint":false},{"pmid":"14615540","id":"PMC_14615540","title":"CLIP identifies Nova-regulated RNA networks in the brain.","date":"2003","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/14615540","citation_count":888,"is_preprint":false},{"pmid":"12110184","id":"PMC_12110184","title":"Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170.","date":"2002","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/12110184","citation_count":502,"is_preprint":false},{"pmid":"16314267","id":"PMC_16314267","title":"CLIP: a method for identifying protein-RNA interaction sites in living cells.","date":"2005","source":"Methods (San Diego, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/16314267","citation_count":475,"is_preprint":false},{"pmid":"11290329","id":"PMC_11290329","title":"Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts.","date":"2001","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/11290329","citation_count":401,"is_preprint":false},{"pmid":"21633356","id":"PMC_21633356","title":"Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data.","date":"2011","source":"Nature biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/21633356","citation_count":331,"is_preprint":false},{"pmid":"21935890","id":"PMC_21935890","title":"HITS-CLIP: panoramic views of protein-RNA regulation in living cells.","date":"2010","source":"Wiley interdisciplinary reviews. 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using high-throughput CLIP and PAR-CLIP sequencing.","date":"2013","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/23368412","citation_count":42,"is_preprint":false},{"pmid":"23118367","id":"PMC_23118367","title":"CLIP (cross-linking and immunoprecipitation) identification of RNAs bound by a specific protein.","date":"2012","source":"Cold Spring Harbor protocols","url":"https://pubmed.ncbi.nlm.nih.gov/23118367","citation_count":36,"is_preprint":false},{"pmid":"36085079","id":"PMC_36085079","title":"Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP.","date":"2022","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/36085079","citation_count":35,"is_preprint":false},{"pmid":"22608712","id":"PMC_22608712","title":"The contribution of CLIP2 haploinsufficiency to the clinical manifestations of the Williams-Beuren syndrome.","date":"2012","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22608712","citation_count":35,"is_preprint":false},{"pmid":"28934506","id":"PMC_28934506","title":"CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome.","date":"2017","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/28934506","citation_count":35,"is_preprint":false},{"pmid":"28254606","id":"PMC_28254606","title":"Computational analysis of CLIP-seq data.","date":"2017","source":"Methods (San Diego, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/28254606","citation_count":34,"is_preprint":false},{"pmid":"33503264","id":"PMC_33503264","title":"A non-radioactive, improved PAR-CLIP and small RNA cDNA library preparation protocol.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/33503264","citation_count":34,"is_preprint":false},{"pmid":"17118263","id":"PMC_17118263","title":"The CLIP-170 orthologue Bik1p and positioning the mitotic spindle in yeast.","date":"2006","source":"Current topics in developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/17118263","citation_count":33,"is_preprint":false},{"pmid":"38982239","id":"PMC_38982239","title":"Decoding protein-RNA interactions using CLIP-based methodologies.","date":"2024","source":"Nature reviews. Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/38982239","citation_count":29,"is_preprint":false},{"pmid":"24777477","id":"PMC_24777477","title":"CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/24777477","citation_count":29,"is_preprint":false},{"pmid":"26577377","id":"PMC_26577377","title":"CLIPSeqTools--a novel bioinformatics CLIP-seq analysis suite.","date":"2015","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/26577377","citation_count":29,"is_preprint":false},{"pmid":"29709556","id":"PMC_29709556","title":"GoldCLIP: Gel-omitted Ligation-dependent CLIP.","date":"2018","source":"Genomics, proteomics & bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/29709556","citation_count":28,"is_preprint":false},{"pmid":"28605404","id":"PMC_28605404","title":"Recent computational developments on CLIP-seq data analysis and microRNA targeting implications.","date":"2018","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/28605404","citation_count":27,"is_preprint":false},{"pmid":"25505146","id":"PMC_25505146","title":"Leveraging cross-link modification events in CLIP-seq for motif discovery.","date":"2014","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/25505146","citation_count":27,"is_preprint":false},{"pmid":"18293353","id":"PMC_18293353","title":"Platinated copper(3-clip-phen) complexes as effective DNA-cleaving and cytotoxic agents.","date":"2008","source":"Chemistry (Weinheim an der Bergstrasse, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/18293353","citation_count":27,"is_preprint":false},{"pmid":"19913027","id":"PMC_19913027","title":"Probing interactions between CLIP-170, EB1, and microtubules.","date":"2009","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19913027","citation_count":27,"is_preprint":false},{"pmid":"25957251","id":"PMC_25957251","title":"Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas.","date":"2015","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/25957251","citation_count":26,"is_preprint":false},{"pmid":"23545196","id":"PMC_23545196","title":"Transcriptome-wide identification of RNA binding sites by CLIP-seq.","date":"2013","source":"Methods (San Diego, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/23545196","citation_count":26,"is_preprint":false},{"pmid":"19687009","id":"PMC_19687009","title":"Cdc2-mediated phosphorylation of CLIP-170 is essential for its inhibition of centrosome reduplication.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19687009","citation_count":25,"is_preprint":false},{"pmid":"37542318","id":"PMC_37542318","title":"Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning.","date":"2023","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/37542318","citation_count":24,"is_preprint":false},{"pmid":"30384847","id":"PMC_30384847","title":"omniCLIP: probabilistic identification of protein-RNA interactions from CLIP-seq data.","date":"2018","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/30384847","citation_count":24,"is_preprint":false},{"pmid":"35189638","id":"PMC_35189638","title":"HCRNet: high-throughput circRNA-binding event identification from CLIP-seq data using deep temporal convolutional network.","date":"2022","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/35189638","citation_count":23,"is_preprint":false},{"pmid":"24178558","id":"PMC_24178558","title":"HITS-CLIP (CLIP-Seq) for mouse Piwi proteins.","date":"2014","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/24178558","citation_count":22,"is_preprint":false},{"pmid":"24940765","id":"PMC_24940765","title":"HITS-CLIP and PAR-CLIP advance viral miRNA targetome analysis.","date":"2014","source":"Critical reviews in eukaryotic gene expression","url":"https://pubmed.ncbi.nlm.nih.gov/24940765","citation_count":21,"is_preprint":false},{"pmid":"30111345","id":"PMC_30111345","title":"Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons.","date":"2018","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/30111345","citation_count":20,"is_preprint":false},{"pmid":"33251722","id":"PMC_33251722","title":"AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP-170.","date":"2020","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/33251722","citation_count":20,"is_preprint":false},{"pmid":"26965263","id":"PMC_26965263","title":"Genome-Wide Profiling of RNA-Protein Interactions Using CLIP-Seq.","date":"2016","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/26965263","citation_count":19,"is_preprint":false},{"pmid":"31947823","id":"PMC_31947823","title":"Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets.","date":"2020","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/31947823","citation_count":19,"is_preprint":false},{"pmid":"29322451","id":"PMC_29322451","title":"Discovering circRNA-microRNA Interactions from CLIP-Seq Data.","date":"2018","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/29322451","citation_count":19,"is_preprint":false},{"pmid":"27222809","id":"PMC_27222809","title":"Identification of CELF1 RNA targets by CLIP-seq in human HeLa cells.","date":"2016","source":"Genomics data","url":"https://pubmed.ncbi.nlm.nih.gov/27222809","citation_count":19,"is_preprint":false},{"pmid":"37851691","id":"PMC_37851691","title":"Serpin-1a and serpin-6 regulate the Toll pathway immune homeostasis by synergistically inhibiting the Spätzle-processing enzyme CLIP2 in silkworm, Bombyx mori.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37851691","citation_count":19,"is_preprint":false},{"pmid":"34819136","id":"PMC_34819136","title":"Functional characterization of two clip domain serine proteases in innate immune responses of Aedes aegypti.","date":"2021","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/34819136","citation_count":19,"is_preprint":false},{"pmid":"25336930","id":"PMC_25336930","title":"Computational Methods for CLIP-seq Data Processing.","date":"2014","source":"Bioinformatics and biology insights","url":"https://pubmed.ncbi.nlm.nih.gov/25336930","citation_count":18,"is_preprint":false},{"pmid":"31863792","id":"PMC_31863792","title":"Identification, characterization, and expression analysis of clip-domain serine protease genes in the silkworm, Bombyx mori.","date":"2019","source":"Developmental and comparative immunology","url":"https://pubmed.ncbi.nlm.nih.gov/31863792","citation_count":18,"is_preprint":false},{"pmid":"36458437","id":"PMC_36458437","title":"CLIP: accurate prediction of disordered linear interacting peptides from protein sequences using co-evolutionary information.","date":"2023","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/36458437","citation_count":18,"is_preprint":false},{"pmid":"27960537","id":"PMC_27960537","title":"Has Sliding-Clip Renorrhaphy Eliminated the Need for Collecting System Repair During Robot-Assisted Partial Nephrectomy?","date":"2017","source":"Journal of endourology","url":"https://pubmed.ncbi.nlm.nih.gov/27960537","citation_count":17,"is_preprint":false},{"pmid":"30455356","id":"PMC_30455356","title":"Mapping multivalency in the CLIP-170-EB1 microtubule plus-end complex.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30455356","citation_count":17,"is_preprint":false},{"pmid":"29747010","id":"PMC_29747010","title":"A clip domain serine protease regulates the expression of proPO and hemolymph clotting in mud crab, Scylla paramamosain.","date":"2018","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/29747010","citation_count":17,"is_preprint":false},{"pmid":"32302342","id":"PMC_32302342","title":"Analysis of the nucleocytoplasmic shuttling RNA-binding protein HNRNPU using optimized HITS-CLIP method.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32302342","citation_count":16,"is_preprint":false},{"pmid":"33372035","id":"PMC_33372035","title":"SOCS3-microtubule interaction via CLIP-170 and CLASP2 is critical for modulation of endothelial inflammation and lung injury.","date":"2021","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/33372035","citation_count":16,"is_preprint":false},{"pmid":"23549612","id":"PMC_23549612","title":"Regulation of tumor angiogenesis by the microtubule-binding protein CLIP-170.","date":"2013","source":"Protein & cell","url":"https://pubmed.ncbi.nlm.nih.gov/23549612","citation_count":16,"is_preprint":false},{"pmid":"29716635","id":"PMC_29716635","title":"CLIP-related methodologies and their application to retrovirology.","date":"2018","source":"Retrovirology","url":"https://pubmed.ncbi.nlm.nih.gov/29716635","citation_count":15,"is_preprint":false},{"pmid":"33357440","id":"PMC_33357440","title":"CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3' UTR Elements.","date":"2020","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/33357440","citation_count":15,"is_preprint":false},{"pmid":"31449064","id":"PMC_31449064","title":"Polypoid Atypical Spitz Tumor With a Fibrosclerotic Stroma, CLIP2-BRAF Fusion, and Homozygous Loss of 9p21.","date":"2020","source":"The American Journal of dermatopathology","url":"https://pubmed.ncbi.nlm.nih.gov/31449064","citation_count":15,"is_preprint":false},{"pmid":"29236251","id":"PMC_29236251","title":"PAR-CLIP for Discovering Target Sites of RNA-Binding Proteins.","date":"2018","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/29236251","citation_count":15,"is_preprint":false},{"pmid":"11593032","id":"PMC_11593032","title":"Specific treatment of autoimmunity with recombinant invariant chains in which CLIP is replaced by self-epitopes.","date":"2001","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11593032","citation_count":15,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":41899,"output_tokens":1808,"usd":0.076409},"stage2":{"model":"claude-opus-4-6","input_tokens":4727,"output_tokens":3475,"usd":0.165765},"total_usd":0.242174,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the human/mammalian CLIP2 gene (also known as CLIP-115, cytoplasmic linker protein 2, encoded by the CLIP2 gene on chromosome 7q11.23 in the Williams-Beuren syndrome region).\n\nKey papers about CLIP-115/CLIP2 (the mammalian microtubule-binding protein):\n- PMID:9427243 (CLIP-115 characterization)\n- PMID:10825300 (CLIP-115 functional analysis)\n- PMID:11290329 (CLASPs as CLIP-115 and -170 associating proteins)\n- PMID:14745832 (LIMK1 and CLIP-115 in Williams syndrome)\n- PMID:22608712 (CLIP2 haploinsufficiency in Williams-Beuren syndrome)\n\nPapers about CLIP-170 (a paralog, CLIP1 gene) should be excluded as they're about a different gene. However, some CLIP-170 papers are directly relevant because they characterize shared mechanisms. I need to be careful — CLIP2 = CLIP-115, not CLIP-170.\n\nLet me carefully extract only CLIP2/CLIP-115 specific findings.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1997,\n      \"finding\": \"CLIP-115 (encoded by CLIP2) was identified as a novel brain-specific cytoplasmic linker protein that contains two N-terminal microtubule-binding domains and a long coiled-coil region. Direct experiments showed CLIP-115 binds microtubules and is enriched in dendritic lamellar bodies (DLBs); local microtubule depolymerization led to a temporary reduction of DLBs, establishing a role for CLIP-115 in brain-specific organelle translocation.\",\n      \"method\": \"cDNA cloning, subcellular fractionation, immunolocalization, microtubule depolymerization experiments in neurons\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — original characterization with multiple orthogonal methods (biochemistry, live imaging, functional perturbation) in a single foundational study\",\n      \"pmids\": [\"9427243\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Efficient microtubule binding by CLIP-115 requires not only the conserved microtubule-binding (MTB) domains but also the flanking basic, serine-rich regions; phosphorylation negatively regulates microtubule binding. CLIP-115 accumulates at distal ends of growing microtubules in transfected COS-1 cells, co-localizing with CLIP-170. CLIP-115 forms homodimers linked by disulfide bridges in vitro, and Cys391 specifically controls microtubule bundling capacity of certain mutants.\",\n      \"method\": \"Transfection of deletion/point mutants in COS-1 cells, microtubule co-sedimentation assays, in vitro phosphorylation, live-cell imaging, in vitro disulfide cross-linking\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal biochemical and cell biological methods including mutagenesis and in vitro reconstitution in a single study\",\n      \"pmids\": [\"10825300\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"CLIP-115 and CLIP-170 associate with two CLIP-associated proteins (CLASPs), homologues of Drosophila Orbit/Mast. CLASPs bind CLIPs and microtubules, co-localize with CLIPs at microtubule distal ends, and have microtubule-stabilizing effects. After serum induction, CLASPs relocalize to distal microtubule segments at the leading edge in a PI3-kinase- and GSK-3β-dependent manner. Antibody injection showed CLASP2 is required for orientation of stabilized microtubules toward the leading edge.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, transfection/overexpression in fibroblasts, antibody microinjection, immunofluorescence microscopy\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP and functional rescue experiments with antibody injection across multiple orthogonal approaches; highly cited foundational study\",\n      \"pmids\": [\"11290329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"CLIP-115 and CLIP-170 are discussed in the context of Williams Syndrome (WBS): knockout mice lacking CLIP-115 show distinct neurological and behavioral phenotypes, consistent with a role for CLIP-115 in the cytoskeletal regulation underlying the neurological symptoms of WBS. The review places CLIP-115 function downstream of microtubule network regulation in a developmental neurological context.\",\n      \"method\": \"Knockout mouse phenotyping (neurological and behavioral analysis) reviewed\",\n      \"journal\": \"BioEssays\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO mouse with defined neurological phenotype, but review paper summarizing prior findings\",\n      \"pmids\": [\"14745832\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Genetic analysis of two healthy siblings with a pure hemizygous deletion of CLIP2 showed no physical or cognitive features of Williams-Beuren syndrome and average IQ without the WBS cognitive profile, demonstrating that CLIP2 haploinsufficiency alone is not sufficient to produce the WBS phenotype or cognitive profile, thus distinguishing CLIP2's contribution from that of GTF2IRD1 and GTF2I.\",\n      \"method\": \"Genomic deletion mapping (array CGH), cognitive testing (IQ assessment) in human patients with isolated CLIP2 hemizygous deletion\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — human genetic loss-of-function with defined cognitive phenotype assessment, but single family/small cohort\",\n      \"pmids\": [\"22608712\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CLIP2 (CLIP-115) is a brain-enriched cytoplasmic linker protein that tracks growing microtubule plus ends via two N-terminal microtubule-binding domains (assisted by flanking basic/serine-rich regions) and a homodimerizing coiled-coil; it localizes to dendritic lamellar bodies and controls their distribution through microtubule association, interacts with CLASP proteins to stabilize microtubules at the cell leading edge in a PI3K/GSK-3β-regulated manner, and its phosphorylation state regulates microtubule binding affinity, while loss-of-function studies in mice reveal neurological and behavioral deficits, though human haploinsufficiency alone does not recapitulate the Williams-Beuren syndrome cognitive profile.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CLIP2 (CLIP-115) is a brain-enriched cytoplasmic linker protein that tracks growing microtubule plus ends via two N-terminal microtubule-binding domains flanked by basic/serine-rich regions required for efficient microtubule association, and forms homodimers through its coiled-coil domain linked by disulfide bridges [PMID:9427243, PMID:10825300]. Phosphorylation negatively regulates its microtubule-binding affinity, and it co-localizes with CLIP-170 at microtubule distal ends; CLIP2 interacts with CLASP proteins that stabilize microtubules at the cell leading edge in a PI3K/GSK-3β-dependent manner [PMID:10825300, PMID:11290329]. In neurons, CLIP2 localizes to dendritic lamellar bodies and controls their distribution through microtubule association; knockout mice lacking CLIP2 exhibit neurological and behavioral deficits, though isolated CLIP2 haploinsufficiency in humans does not recapitulate the Williams-Beuren syndrome cognitive profile [PMID:9427243, PMID:14745832, PMID:22608712].\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Establishing that CLIP2 is a brain-specific microtubule-binding protein linked to organelle positioning resolved its molecular identity and provided the first functional context — localizing to dendritic lamellar bodies whose distribution depends on intact microtubules.\",\n      \"evidence\": \"cDNA cloning, subcellular fractionation, immunolocalization, and microtubule depolymerization experiments in neurons\",\n      \"pmids\": [\"9427243\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis for microtubule-binding domain selectivity was unresolved\",\n        \"Regulatory signals controlling CLIP-115 activity were unknown\",\n        \"In vivo loss-of-function phenotype had not been determined\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Dissecting the domain requirements for microtubule binding showed that flanking basic/serine-rich regions are necessary beyond the conserved MTB domains, that phosphorylation inhibits binding, and that CLIP-115 homodimerizes via disulfide bridges — establishing key regulatory and structural principles.\",\n      \"evidence\": \"Deletion/point mutant transfection in COS-1 cells, microtubule co-sedimentation, in vitro phosphorylation, and disulfide cross-linking\",\n      \"pmids\": [\"10825300\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of the kinase(s) responsible for regulatory phosphorylation was unknown\",\n        \"Functional significance of CLIP-115/CLIP-170 co-localization at plus ends remained unresolved\",\n        \"Whether dimerization is required for in vivo function was untested\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identifying CLASPs as CLIP-115/CLIP-170 interactors that stabilize microtubules at the leading edge downstream of PI3K and GSK-3β placed CLIP2 within a signaling-regulated plus-end complex controlling cell polarity.\",\n      \"evidence\": \"Yeast two-hybrid, co-immunoprecipitation, overexpression in fibroblasts, and antibody microinjection\",\n      \"pmids\": [\"11290329\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the CLIP-115–CLASP interaction is direct or bridged was not fully resolved\",\n        \"Relative contributions of CLIP-115 versus CLIP-170 in recruiting CLASPs were unclear\",\n        \"Neuronal relevance of the PI3K/GSK-3β–CLASP–CLIP axis was not tested\"\n      ]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrating that CLIP-115 knockout mice display neurological and behavioral deficits established that the protein's microtubule-regulatory function is essential for normal brain development and behavior.\",\n      \"evidence\": \"Knockout mouse phenotyping with neurological and behavioral analysis (reviewed)\",\n      \"pmids\": [\"14745832\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Primary data were presented in a review context; detailed mechanistic dissection of neuronal deficits was lacking\",\n        \"Which neuronal cell types or circuits are most affected was unresolved\",\n        \"Relationship between microtubule dynamics defects and behavioral outcomes was correlative\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showing that isolated human CLIP2 haploinsufficiency does not produce the Williams-Beuren syndrome cognitive profile distinguished CLIP2's contribution from that of GTF2IRD1/GTF2I and refined the genotype–phenotype map of the WBS deletion region.\",\n      \"evidence\": \"Array CGH deletion mapping and cognitive testing in siblings with pure CLIP2 hemizygous deletion\",\n      \"pmids\": [\"22608712\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Only a single family was studied, limiting generalizability\",\n        \"Subtle neurological phenotypes below the resolution of standard cognitive testing could be missed\",\n        \"Whether CLIP2 loss interacts epistatically with other WBS-region gene deletions was not tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo kinase(s) regulating CLIP2 phosphorylation, the structural basis for its selective plus-end tracking, and the specific neuronal circuits and developmental processes disrupted by CLIP2 loss remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No kinase or phosphatase acting on CLIP2 has been identified in vivo\",\n        \"No high-resolution structure of CLIP2 microtubule-binding domains exists\",\n        \"The neuronal cell-type-specific functions of CLIP2 are undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"CLIP1\",\n      \"CLASP1\",\n      \"CLASP2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait — I need to correct the pathway slot. Pathway should use Reactome term_ids, not GO. Let me fix:\n\n```json\n{\n  \"mechanistic_narrative\": \"CLIP2 (CLIP-115) is a brain-enriched cytoplasmic linker protein that tracks growing microtubule plus ends via two N-terminal microtubule-binding domains flanked by basic/serine-rich regions required for efficient microtubule association, and forms homodimers through its coiled-coil domain linked by disulfide bridges [PMID:9427243, PMID:10825300]. Phosphorylation negatively regulates its microtubule-binding affinity, and it co-localizes with CLIP-170 at microtubule distal ends; CLIP2 interacts with CLASP proteins that stabilize microtubules at the cell leading edge in a PI3K/GSK-3β-dependent manner [PMID:10825300, PMID:11290329]. In neurons, CLIP2 localizes to dendritic lamellar bodies and controls their distribution through microtubule association; knockout mice lacking CLIP2 exhibit neurological and behavioral deficits, though isolated CLIP2 haploinsufficiency in humans does not recapitulate the Williams-Beuren syndrome cognitive profile [PMID:9427243, PMID:14745832, PMID:22608712].\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Establishing that CLIP2 is a brain-specific microtubule-binding protein linked to organelle positioning resolved its molecular identity and provided the first functional context — localizing to dendritic lamellar bodies whose distribution depends on intact microtubules.\",\n      \"evidence\": \"cDNA cloning, subcellular fractionation, immunolocalization, and microtubule depolymerization experiments in neurons\",\n      \"pmids\": [\"9427243\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis for microtubule-binding domain selectivity was unresolved\",\n        \"Regulatory signals controlling CLIP-115 activity were unknown\",\n        \"In vivo loss-of-function phenotype had not been determined\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Dissecting the domain requirements for microtubule binding showed that flanking basic/serine-rich regions are necessary beyond the conserved MTB domains, that phosphorylation inhibits binding, and that CLIP-115 homodimerizes via disulfide bridges — establishing key regulatory and structural principles.\",\n      \"evidence\": \"Deletion/point mutant transfection in COS-1 cells, microtubule co-sedimentation, in vitro phosphorylation, and disulfide cross-linking\",\n      \"pmids\": [\"10825300\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of the kinase(s) responsible for regulatory phosphorylation was unknown\",\n        \"Functional significance of CLIP-115/CLIP-170 co-localization at plus ends remained unresolved\",\n        \"Whether dimerization is required for in vivo function was untested\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identifying CLASPs as CLIP-115/CLIP-170 interactors that stabilize microtubules at the leading edge downstream of PI3K and GSK-3β placed CLIP2 within a signaling-regulated plus-end complex controlling cell polarity.\",\n      \"evidence\": \"Yeast two-hybrid, co-immunoprecipitation, overexpression in fibroblasts, and antibody microinjection\",\n      \"pmids\": [\"11290329\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the CLIP-115–CLASP interaction is direct or bridged was not fully resolved\",\n        \"Relative contributions of CLIP-115 versus CLIP-170 in recruiting CLASPs were unclear\",\n        \"Neuronal relevance of the PI3K/GSK-3β–CLASP–CLIP axis was not tested\"\n      ]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrating that CLIP-115 knockout mice display neurological and behavioral deficits established that the protein's microtubule-regulatory function is essential for normal brain development and behavior.\",\n      \"evidence\": \"Knockout mouse phenotyping with neurological and behavioral analysis (reviewed)\",\n      \"pmids\": [\"14745832\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Primary data were presented in a review context; detailed mechanistic dissection of neuronal deficits was lacking\",\n        \"Which neuronal cell types or circuits are most affected was unresolved\",\n        \"Relationship between microtubule dynamics defects and behavioral outcomes was correlative\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showing that isolated human CLIP2 haploinsufficiency does not produce the Williams-Beuren syndrome cognitive profile distinguished CLIP2's contribution from that of GTF2IRD1/GTF2I and refined the genotype–phenotype map of the WBS deletion region.\",\n      \"evidence\": \"Array CGH deletion mapping and cognitive testing in siblings with pure CLIP2 hemizygous deletion\",\n      \"pmids\": [\"22608712\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Only a single family was studied, limiting generalizability\",\n        \"Subtle neurological phenotypes below the resolution of standard cognitive testing could be missed\",\n        \"Whether CLIP2 loss interacts epistatically with other WBS-region gene deletions was not tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo kinase(s) regulating CLIP2 phosphorylation, the structural basis for its selective plus-end tracking, and the specific neuronal circuits and developmental processes disrupted by CLIP2 loss remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No kinase or phosphatase acting on CLIP2 has been identified in vivo\",\n        \"No high-resolution structure of CLIP2 microtubule-binding domains exists\",\n        \"The neuronal cell-type-specific functions of CLIP2 are undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"CLIP1\",\n      \"CLASP1\",\n      \"CLASP2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}