{"gene":"PPFIBP1","run_date":"2026-04-28T19:45:44","timeline":{"discoveries":[{"year":1998,"finding":"PPFIBP1 (liprin-β1) was identified as a member of the liprin family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. The C-terminal non-coiled-coil region of alpha-liprins binds to the membrane-distal phosphatase domains of LAR family members, and alpha-liprins also bind to the C-terminal non-coiled-coil region of beta-liprins (including PPFIBP1). Both alpha- and beta-liprins homodimerize via their N-terminal coiled-coil regions, establishing that liprins are multivalent proteins. Co-expression studies showed that liprin-alpha2 alters LAR cellular localization and induces LAR clustering, implicating liprins in localizing LAR family phosphatases at specific plasma membrane sites.","method":"Yeast two-hybrid, co-immunoprecipitation, co-expression localization studies, domain mapping","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal binding assays, domain mapping, and functional localization studies in a single foundational paper with multiple orthogonal methods","pmids":["9624153"],"is_preprint":false},{"year":2011,"finding":"PPFIBP1 (liprin-β1) was identified as a component of cortical microtubule attachment complexes. KIF21A is recruited to the cell cortex by KANK1, which co-clusters with liprin-α1/β1 and components of LL5β-containing complexes, placing liprin-β1 (PPFIBP1) within a multi-protein cortical complex that regulates microtubule growth at the cell periphery.","method":"Affinity proteomics, co-immunoprecipitation, confocal microscopy, functional rescue assays","journal":"Developmental cell","confidence":"Medium","confidence_rationale":"Tier 2 — co-IP and imaging place PPFIBP1 in the complex, but the direct functional role of PPFIBP1 specifically was not individually dissected","pmids":["24120883"],"is_preprint":false},{"year":2011,"finding":"PPFIBP1 was identified as part of the myosin-II-responsive focal adhesion proteome; its abundance in focal adhesions changes with myosin II activity, placing it within the contractility-regulated focal adhesion compartment.","method":"Quantitative proteomic analysis of isolated focal adhesions with and without myosin II inhibition (blebbistatin), mass spectrometry","journal":"Nature cell biology","confidence":"Low","confidence_rationale":"Tier 3 — PPFIBP1 detected in proteomics screen; no direct functional follow-up of PPFIBP1 specifically in this study","pmids":["21423176"],"is_preprint":false},{"year":2011,"finding":"PPFIBP1 was identified as a novel ALK fusion partner (PPFIBP1-ALK) in pulmonary inflammatory myofibroblastic tumor (IMT). The PPFIBP1-ALK fusion was confirmed by 5'-RACE, RT-PCR, genomic PCR, and FISH. The fusion protein demonstrated transforming activity in NIH 3T3 fibroblasts in a focus formation assay and in an in vivo tumorigenicity assay using a recombinant retrovirus, establishing that PPFIBP1-ALK is an oncogenic fusion kinase.","method":"5'-RACE, RT-PCR, genomic PCR, FISH, focus formation assay, in vivo tumorigenicity assay in NIH 3T3 fibroblasts","journal":"Clinical cancer research : an official journal of the American Association for Cancer Research","confidence":"High","confidence_rationale":"Tier 1-2 — transforming activity confirmed by both in vitro focus formation and in vivo tumorigenicity assays with molecular confirmation by multiple methods","pmids":["21430068"],"is_preprint":false},{"year":2021,"finding":"PPFIBP1 promotes glioma cell migration and invasion through activation of the FAK/Src/JNK signaling pathway. Overexpression of PPFIBP1 activated FAK, Src, JNK, and c-Jun, enhancing MMP-2 expression, while knockdown inhibited invasion and migration in scratch and transwell assays. The mechanism involves interaction with SRCIN1 (p140Cap). Pharmacological inhibition of FAK and Src phosphorylation reversed the pro-invasive effects of PPFIBP1 overexpression. In xenograft models, PPFIBP1 overexpression facilitated tumor infiltration and reduced survival.","method":"Scratch assay, transwell invasion assay, RNA-seq, GO enrichment, Western blotting for pathway activation, pharmacological inhibition, xenograft mouse model, co-immunoprecipitation with SRCIN1","journal":"Cell death & disease","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods including KD/OE with defined phenotype, pathway identification, interacting partner identification, and in vivo validation","pmids":["34480020"],"is_preprint":false}],"current_model":"PPFIBP1 (liprin-β1) is a multivalent scaffold protein that heterodimerizes with alpha-liprins and participates in localizing LAR-family receptor tyrosine phosphatases at the plasma membrane; it also forms part of cortical microtubule attachment complexes via KANK1, and in cancer cells activates FAK/Src/JNK/c-Jun signaling to promote invasion and MMP-2 expression through interaction with SRCIN1, while its N-terminal coiled-coil drives dimerization and its C-terminal domain mediates liprin-alpha binding."},"narrative":{"teleology":[{"year":1998,"claim":"The founding question of how LAR-family receptor phosphatases are localized at the plasma membrane was answered by identifying PPFIBP1 (liprin-β1) as a member of the liprin family that heterodimerizes with liprin-α proteins and participates in LAR clustering, establishing the multivalent scaffold model for phosphatase localization.","evidence":"Yeast two-hybrid, co-immunoprecipitation, domain mapping, and co-expression localization studies","pmids":["9624153"],"confidence":"High","gaps":["Whether liprin-β1 directly contacts LAR or only bridges via liprin-α remains unresolved","No structural data for the liprin-β1/liprin-α interface","Functional consequence of liprin-β1 loss on LAR signaling was not tested"]},{"year":2011,"claim":"Placing PPFIBP1 within cortical microtubule attachment complexes containing KANK1, liprin-α1, and LL5β expanded its functional context from phosphatase scaffolding to regulation of microtubule capture at the cell periphery, while proteomic detection in focal adhesions linked it to the mechanosensitive adhesion compartment.","evidence":"Affinity proteomics, co-immunoprecipitation, confocal microscopy, and quantitative focal adhesion proteomics","pmids":["24120883","21423176"],"confidence":"Medium","gaps":["The specific functional contribution of PPFIBP1 to cortical microtubule attachment was not individually dissected","Focal adhesion detection was proteomics-based without direct functional follow-up for PPFIBP1","Whether PPFIBP1's role in cortical complexes is independent of its LAR-scaffolding function is unknown"]},{"year":2011,"claim":"Identification of the PPFIBP1-ALK fusion in inflammatory myofibroblastic tumor demonstrated that the PPFIBP1 locus can serve as an oncogenic fusion partner, with the chimeric protein showing transforming activity both in vitro and in vivo.","evidence":"5'-RACE, RT-PCR, FISH confirmation, NIH 3T3 focus formation assay, and in vivo tumorigenicity assay","pmids":["21430068"],"confidence":"High","gaps":["Whether the coiled-coil domain of PPFIBP1 drives constitutive dimerization of the fusion kinase was not tested","Prevalence of this fusion across tumor types beyond IMT is not established in this study"]},{"year":2021,"claim":"The mechanism by which PPFIBP1 promotes cancer cell invasion was resolved: interaction with SRCIN1 activates FAK/Src/JNK/c-Jun signaling, upregulating MMP-2 and driving glioma cell migration, invasion, and in vivo tumor infiltration.","evidence":"Knockdown/overexpression, transwell and scratch assays, co-immunoprecipitation with SRCIN1, pharmacological pathway inhibition, and xenograft models in glioma cells","pmids":["34480020"],"confidence":"High","gaps":["Whether the SRCIN1–FAK/Src axis operates in non-glioma contexts is untested","The structural basis of the PPFIBP1–SRCIN1 interaction is unknown","Relationship between the LAR-scaffolding and SRCIN1-mediated invasion functions has not been explored"]},{"year":null,"claim":"How PPFIBP1's distinct interaction networks—LAR phosphatase scaffolding, cortical microtubule attachment, and SRCIN1-mediated invasion signaling—are coordinated or segregated in different cellular contexts remains an open question.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structure of PPFIBP1 or its complexes is available","Whether liprin-β1 has catalytic or enzymatic activity independent of scaffolding is unknown","Tissue-specific functions and knockout phenotypes in mammalian models are poorly characterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,4]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4]}],"complexes":["Liprin-α/β complex","KANK1–liprin–LL5β cortical complex"],"partners":["PPFIA1","PPFIA2","KANK1","SRCIN1","PTPRF"],"other_free_text":[]},"mechanistic_narrative":"PPFIBP1 (liprin-β1) is a multivalent scaffold protein that heterodimerizes with liprin-α family members through its C-terminal non-coiled-coil region and homodimerizes via its N-terminal coiled-coil domain, functioning to localize LAR-family receptor tyrosine phosphatases at specific plasma membrane sites [PMID:9624153]. It is a component of cortical microtubule attachment complexes containing KANK1, liprin-α1, and LL5β, linking it to regulation of microtubule dynamics at the cell periphery [PMID:24120883]. In glioma cells, PPFIBP1 promotes migration and invasion by interacting with SRCIN1 and activating FAK/Src/JNK/c-Jun signaling to upregulate MMP-2 expression, and its overexpression enhances tumor infiltration and reduces survival in xenograft models [PMID:34480020]."},"prefetch_data":{"uniprot":{"accession":"Q86W92","full_name":"Liprin-beta-1","aliases":["Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 1","PTPRF-interacting protein-binding protein 1","hSGT2"],"length_aa":1011,"mass_kda":114.0,"function":"May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A","subcellular_location":"Cytoplasm, cell cortex","url":"https://www.uniprot.org/uniprotkb/Q86W92/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PPFIBP1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2},{"gene":"DYNLL1","stoichiometry":0.2},{"gene":"DYNLL2","stoichiometry":0.2},{"gene":"PPP2CA","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PPFIBP1","total_profiled":1310},"omim":[{"mim_id":"620024","title":"NEURODEVELOPMENTAL DISORDER WITH SEIZURES, MICROCEPHALY, AND BRAIN ABNORMALITIES; NEDSMBA","url":"https://www.omim.org/entry/620024"},{"mim_id":"611054","title":"PTPRF-INTERACTING PROTEIN ALPHA-1; PPFIA1","url":"https://www.omim.org/entry/611054"},{"mim_id":"603141","title":"PPFIA-BINDING PROTEIN 1; PPFIBP1","url":"https://www.omim.org/entry/603141"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PPFIBP1"},"hgnc":{"alias_symbol":["L2","hSGT2","hSgt2p","SGT2","liprin-beta1"],"prev_symbol":[]},"alphafold":{"accession":"Q86W92","domains":[{"cath_id":"1.10.150.50","chopping":"765-903","consensus_level":"medium","plddt":92.2983,"start":765,"end":903}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86W92","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86W92-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86W92-F1-predicted_aligned_error_v6.png","plddt_mean":67.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PPFIBP1","jax_strain_url":"https://www.jax.org/strain/search?query=PPFIBP1"},"sequence":{"accession":"Q86W92","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86W92.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86W92/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86W92"}},"corpus_meta":[{"pmid":"11224527","id":"PMC_11224527","title":"PD-L2 is a second ligand for PD-1 and inhibits T cell activation.","date":"2001","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11224527","citation_count":2344,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28494868","id":"PMC_28494868","title":"Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/28494868","citation_count":1448,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27069084","id":"PMC_27069084","title":"PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome.","date":"2016","source":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/27069084","citation_count":644,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12697896","id":"PMC_12697896","title":"PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12697896","citation_count":518,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28619999","id":"PMC_28619999","title":"PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer.","date":"2017","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/28619999","citation_count":491,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18367526","id":"PMC_18367526","title":"Arrangement of L2 within the papillomavirus capsid.","date":"2008","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/18367526","citation_count":271,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24752301","id":"PMC_24752301","title":"RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance.","date":"2014","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/24752301","citation_count":269,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23689062","id":"PMC_23689062","title":"L2, the minor capsid protein of papillomavirus.","date":"2013","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/23689062","citation_count":179,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17889673","id":"PMC_17889673","title":"E1-L2 activates both ubiquitin and FAT10.","date":"2007","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/17889673","citation_count":161,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37138075","id":"PMC_37138075","title":"Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance.","date":"2023","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/37138075","citation_count":153,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"14615595","id":"PMC_14615595","title":"Adenosine kinase is inactivated by geminivirus AL2 and L2 proteins.","date":"2003","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/14615595","citation_count":148,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26081225","id":"PMC_26081225","title":"Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma.","date":"2015","source":"Cancer immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/26081225","citation_count":121,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12663788","id":"PMC_12663788","title":"Interactions between papillomavirus L1 and L2 capsid proteins.","date":"2003","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/12663788","citation_count":109,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20722638","id":"PMC_20722638","title":"Role of PD-L1 and PD-L2 in allergic diseases and asthma.","date":"2010","source":"Allergy","url":"https://pubmed.ncbi.nlm.nih.gov/20722638","citation_count":104,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18216018","id":"PMC_18216018","title":"Characterization of cyclin L1 and L2 interactions with CDK11 and splicing factors: influence of cyclin L isoforms on splice site selection.","date":"2008","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18216018","citation_count":102,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9210666","id":"PMC_9210666","title":"Sequence analysis and enzyme kinetics of the L2 serine beta-lactamase from Stenotrophomonas maltophilia.","date":"1997","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/9210666","citation_count":96,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33849617","id":"PMC_33849617","title":"CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer.","date":"2021","source":"Journal of hematology & oncology","url":"https://pubmed.ncbi.nlm.nih.gov/33849617","citation_count":95,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1438223","id":"PMC_1438223","title":"Macrophages in Drosophila embryos and L2 cells exhibit scavenger receptor-mediated endocytosis.","date":"1992","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/1438223","citation_count":88,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35530130","id":"PMC_35530130","title":"The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation.","date":"2021","source":"Acta pharmaceutica Sinica. B","url":"https://pubmed.ncbi.nlm.nih.gov/35530130","citation_count":86,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12610128","id":"PMC_12610128","title":"Cell surface-binding motifs of L2 that facilitate papillomavirus infection.","date":"2003","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/12610128","citation_count":82,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38267628","id":"PMC_38267628","title":"The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2.","date":"2024","source":"Nature cancer","url":"https://pubmed.ncbi.nlm.nih.gov/38267628","citation_count":81,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12208958","id":"PMC_12208958","title":"Protective immunity to rabbit oral and cutaneous papillomaviruses by immunization with short peptides of L2, the minor capsid protein.","date":"2002","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/12208958","citation_count":81,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36522474","id":"PMC_36522474","title":"Evolving landscape of PD-L2: bring new light to checkpoint immunotherapy.","date":"2022","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/36522474","citation_count":80,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21430068","id":"PMC_21430068","title":"Pulmonary inflammatory myofibroblastic tumor expressing a novel fusion, PPFIBP1-ALK: reappraisal of anti-ALK immunohistochemistry as a tool for novel ALK fusion identification.","date":"2011","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/21430068","citation_count":78,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31076547","id":"PMC_31076547","title":"Immune Suppression by PD-L2 against Spontaneous and Treatment-Related Antitumor Immunity.","date":"2019","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/31076547","citation_count":77,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34697216","id":"PMC_34697216","title":"PD-L2 glycosylation promotes immune evasion and predicts anti-EGFR efficacy.","date":"2021","source":"Journal for immunotherapy of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/34697216","citation_count":76,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20106980","id":"PMC_20106980","title":"Crystal structure of Get4-Get5 complex and its interactions with Sgt2, Get3, and Ydj1.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20106980","citation_count":76,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15140951","id":"PMC_15140951","title":"Nuclear translocation of papillomavirus minor capsid protein L2 requires Hsc70.","date":"2004","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/15140951","citation_count":71,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31882544","id":"PMC_31882544","title":"The structural features that distinguish PD-L2 from PD-L1 emerged in placental mammals.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31882544","citation_count":70,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31709703","id":"PMC_31709703","title":"TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease.","date":"2019","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/31709703","citation_count":69,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24485762","id":"PMC_24485762","title":"Synthesis of L-2,3-diaminopropionic acid, a siderophore and antibiotic precursor.","date":"2014","source":"Chemistry & biology","url":"https://pubmed.ncbi.nlm.nih.gov/24485762","citation_count":65,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25349132","id":"PMC_25349132","title":"PD-1, PD-L1, PD-L2 expression in the chordoma microenvironment.","date":"2014","source":"Journal of neuro-oncology","url":"https://pubmed.ncbi.nlm.nih.gov/25349132","citation_count":65,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26202251","id":"PMC_26202251","title":"A Novel PDZ Domain Interaction Mediates the Binding between Human Papillomavirus 16 L2 and Sorting Nexin 27 and Modulates Virion Trafficking.","date":"2015","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/26202251","citation_count":64,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7523300","id":"PMC_7523300","title":"Chlamydia trachomatis serovar L2 induces protein tyrosine phosphorylation during uptake by HeLa cells.","date":"1994","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/7523300","citation_count":62,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19414581","id":"PMC_19414581","title":"AmpDI is involved in expression of the chromosomal L1 and L2 beta-lactamases of Stenotrophomonas maltophilia.","date":"2009","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/19414581","citation_count":61,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27889616","id":"PMC_27889616","title":"Developments in L2-based human papillomavirus (HPV) vaccines.","date":"2016","source":"Virus research","url":"https://pubmed.ncbi.nlm.nih.gov/27889616","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23142665","id":"PMC_23142665","title":"Structures of the Sgt2/SGTA dimerization domain with the Get5/UBL4A UBL domain reveal an interaction that forms a conserved dynamic interface.","date":"2012","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/23142665","citation_count":56,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9568045","id":"PMC_9568045","title":"DNA packaging by L1 and L2 capsid proteins of bovine papillomavirus type 1.","date":"1998","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/9568045","citation_count":55,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35365585","id":"PMC_35365585","title":"Genetic characteristics involving the PD-1/PD-L1/L2 and CD73/A2aR axes and the immunosuppressive microenvironment in DLBCL.","date":"2022","source":"Journal for immunotherapy of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/35365585","citation_count":52,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26538022","id":"PMC_26538022","title":"A complex of Rab13 with MICAL-L2 and α-actinin-4 is essential for insulin-dependent GLUT4 exocytosis.","date":"2015","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/26538022","citation_count":52,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29207511","id":"PMC_29207511","title":"Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2.","date":"2017","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/29207511","citation_count":51,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34011561","id":"PMC_34011561","title":"Neutralization of PD-L2 is Essential for Overcoming Immune Checkpoint Blockade Resistance in Ovarian Cancer.","date":"2021","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/34011561","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9274877","id":"PMC_9274877","title":"Isolation of a cDNA encoding Fasciola hepatica cathepsin L2 and functional expression in Saccharomyces cerevisiae.","date":"1997","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9274877","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29038297","id":"PMC_29038297","title":"Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer.","date":"2017","source":"Cancer immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/29038297","citation_count":49,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23045389","id":"PMC_23045389","title":"Regulation of chaperone effects on a yeast prion by cochaperone Sgt2.","date":"2012","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/23045389","citation_count":49,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31877975","id":"PMC_31877975","title":"Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?","date":"2019","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/31877975","citation_count":48,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16780572","id":"PMC_16780572","title":"Roles of the human Rad51 L1 and L2 loops in DNA binding.","date":"2006","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/16780572","citation_count":48,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11815585","id":"PMC_11815585","title":"Differential regulation of L1 and L2 beta-lactamase expression in Stenotrophomonas maltophilia.","date":"2002","source":"The Journal of antimicrobial chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/11815585","citation_count":47,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20407010","id":"PMC_20407010","title":"LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity.","date":"2010","source":"American journal of physiology. Endocrinology and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/20407010","citation_count":47,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20727857","id":"PMC_20727857","title":"Ribosomal protein L2 associates with E. coli HtpG and activates its ATPase activity.","date":"2010","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/20727857","citation_count":47,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23149662","id":"PMC_23149662","title":"PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production.","date":"2012","source":"Mucosal immunology","url":"https://pubmed.ncbi.nlm.nih.gov/23149662","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11040122","id":"PMC_11040122","title":"Interaction of the papillomavirus transcription/replication factor, E2, and the viral capsid protein, L2.","date":"2000","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/11040122","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24816794","id":"PMC_24816794","title":"Impact of inhibitors and L2 antibodies upon the infectivity of diverse alpha and beta human papillomavirus types.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24816794","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25864591","id":"PMC_25864591","title":"Silencing of MICAL-L2 suppresses malignancy of ovarian cancer by inducing mesenchymal-epithelial transition.","date":"2015","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/25864591","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17869365","id":"PMC_17869365","title":"Human papillomavirus 16 E6, L1, L2 and E2 gene variants in cervical lesion progression.","date":"2007","source":"Virus research","url":"https://pubmed.ncbi.nlm.nih.gov/17869365","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30546952","id":"PMC_30546952","title":"Identification of PD-L2, B7-H3 and CTLA-4 immune checkpoint proteins in genetic subtypes of meningioma.","date":"2018","source":"Oncoimmunology","url":"https://pubmed.ncbi.nlm.nih.gov/30546952","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"39103634","id":"PMC_39103634","title":"A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.","date":"2024","source":"Nature chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/39103634","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27122588","id":"PMC_27122588","title":"Furin Cleavage of L2 during Papillomavirus Infection: Minimal Dependence on Cyclophilins.","date":"2016","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/27122588","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8722025","id":"PMC_8722025","title":"Histidine 229 in protein L2 is apparently essential for 50S peptidyl transferase activity.","date":"1995","source":"Biochemistry and cell biology = Biochimie et biologie cellulaire","url":"https://pubmed.ncbi.nlm.nih.gov/8722025","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27045038","id":"PMC_27045038","title":"The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation.","date":"2016","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/27045038","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33802456","id":"PMC_33802456","title":"RG1-VLP and Other L2-Based, Broad-Spectrum HPV Vaccine Candidates.","date":"2021","source":"Journal of clinical medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33802456","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32367440","id":"PMC_32367440","title":"Immune suppression caused by PD-L2 expression on tumor cells in gastric cancer.","date":"2020","source":"Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association","url":"https://pubmed.ncbi.nlm.nih.gov/32367440","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34480020","id":"PMC_34480020","title":"PPFIBP1 induces glioma cell migration and invasion through FAK/Src/JNK signaling pathway.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/34480020","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12472892","id":"PMC_12472892","title":"Identification of a peptide mimic of the L2/HNK-1 carbohydrate epitope.","date":"2002","source":"Journal of neurochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12472892","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17593967","id":"PMC_17593967","title":"Expression, processing, and localization of PmpD of Chlamydia trachomatis Serovar L2 during the chlamydial developmental cycle.","date":"2007","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/17593967","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19169853","id":"PMC_19169853","title":"Insights into the role and function of L2, the minor capsid protein of papillomaviruses.","date":"2009","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/19169853","citation_count":36,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34957697","id":"PMC_34957697","title":"FasL+ PD-L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression.","date":"2021","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/34957697","citation_count":36,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29212932","id":"PMC_29212932","title":"Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and Mucosal Human Papillomaviruses.","date":"2018","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/29212932","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31034158","id":"PMC_31034158","title":"MICAL-L2 potentiates Cdc42-dependent EGFR stability and promotes gastric cancer cell migration.","date":"2019","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31034158","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3062369","id":"PMC_3062369","title":"Gene dosage alteration of L2 ribosomal protein genes in Saccharomyces cerevisiae: effects on ribosome synthesis.","date":"1988","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/3062369","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25975355","id":"PMC_25975355","title":"Tick sialostatins L and L2 differentially influence dendritic cell responses to Borrelia spirochetes.","date":"2015","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/25975355","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3061801","id":"PMC_3061801","title":"The binding site for ribosomal protein L2 within 23S ribosomal RNA of Escherichia coli.","date":"1988","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/3061801","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17891173","id":"PMC_17891173","title":"Involvement of Rab13 and JRAB/MICAL-L2 in epithelial cell scattering.","date":"2007","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/17891173","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25445910","id":"PMC_25445910","title":"Cxcl8-l1 and Cxcl8-l2 are required in the zebrafish defense against Salmonella Typhimurium.","date":"2014","source":"Developmental and comparative immunology","url":"https://pubmed.ncbi.nlm.nih.gov/25445910","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31209107","id":"PMC_31209107","title":"Structural and biochemical characterization of 20β-hydroxysteroid dehydrogenase from Bifidobacterium adolescentis strain L2-32.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31209107","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12209911","id":"PMC_12209911","title":"Cytotoxicity of ingredients of various dental materials and related compounds in L2- and A549 cells.","date":"2002","source":"Journal of biomedical materials research","url":"https://pubmed.ncbi.nlm.nih.gov/12209911","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20385866","id":"PMC_20385866","title":"AmpN-AmpG operon is essential for expression of L1 and L2 beta-lactamases in Stenotrophomonas maltophilia.","date":"2010","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/20385866","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21619481","id":"PMC_21619481","title":"Cooperative and independent activities of Sgt2 and Get5 in the targeting of tail-anchored proteins.","date":"2011","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21619481","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23297211","id":"PMC_23297211","title":"Structure of the Sgt2/Get5 complex provides insights into GET-mediated targeting of tail-anchored membrane proteins.","date":"2013","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/23297211","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25552721","id":"PMC_25552721","title":"Analysis of geminivirus AL2 and L2 proteins reveals a novel AL2 silencing suppressor activity.","date":"2014","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/25552721","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7491757","id":"PMC_7491757","title":"Sequences required for the nuclear targeting and accumulation of human papillomavirus type 6B L2 protein.","date":"1995","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/7491757","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27069956","id":"PMC_27069956","title":"PD-1, PD-L1 and PD-L2 expression in mouse prostate cancer.","date":"2016","source":"American journal of clinical and experimental urology","url":"https://pubmed.ncbi.nlm.nih.gov/27069956","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32439434","id":"PMC_32439434","title":"Optimization production of exopolysaccharide from Leuconostoc lactis L2 and its partial characterization.","date":"2020","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/32439434","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34193420","id":"PMC_34193420","title":"Retromer stabilizes transient membrane insertion of L2 capsid protein during retrograde entry of human papillomavirus.","date":"2021","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/34193420","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24376539","id":"PMC_24376539","title":"TLR2 directing PD-L2 expression inhibit T cells response in Schistosoma japonicum infection.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24376539","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21288885","id":"PMC_21288885","title":"Two forms of ribosomal protein L2 of Escherichia coli that inhibit DnaA in DNA replication.","date":"2011","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/21288885","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33542241","id":"PMC_33542241","title":"Ribosome-bound Get4/5 facilitates the capture of tail-anchored proteins by Sgt2 in yeast.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/33542241","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33019516","id":"PMC_33019516","title":"Progress in L2-Based Prophylactic Vaccine Development for Protection against Diverse Human Papillomavirus Genotypes and Associated Diseases.","date":"2020","source":"Vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/33019516","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30559738","id":"PMC_30559738","title":"Hantavirus-Driven PD-L1/PD-L2 Upregulation: An Imperfect Viral Immune Evasion Mechanism.","date":"2018","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30559738","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23372836","id":"PMC_23372836","title":"Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23372836","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30464512","id":"PMC_30464512","title":"Clinicopathological analysis of PD-L2 expression in colorectal cancer.","date":"2018","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/30464512","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33990697","id":"PMC_33990697","title":"PD-L2 suppresses T cell signaling via coinhibitory microcluster formation and SHP2 phosphatase recruitment.","date":"2021","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/33990697","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32493985","id":"PMC_32493985","title":"GATA2 Regulates Constitutive PD-L1 and PD-L2 Expression in Brain Tumors.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32493985","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26901354","id":"PMC_26901354","title":"Progress and prospects for L2-based human papillomavirus vaccines.","date":"2016","source":"Expert review of vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/26901354","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35604352","id":"PMC_35604352","title":"Diacylglycerols interact with the L2 lipidation site in TRPC3 to induce a sensitized channel state.","date":"2022","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/35604352","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25972404","id":"PMC_25972404","title":"Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2-Specific Human Chimeric Monoclonal Antibodies.","date":"2015","source":"Clinical and vaccine immunology : CVI","url":"https://pubmed.ncbi.nlm.nih.gov/25972404","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19559114","id":"PMC_19559114","title":"Immunogenicity of an HPV-16 L2 DNA vaccine.","date":"2009","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/19559114","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33610544","id":"PMC_33610544","title":"Molecular basis of tail-anchored integral membrane protein recognition by the cochaperone Sgt2.","date":"2021","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/33610544","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33888511","id":"PMC_33888511","title":"Comprehensive characterization of tissue-specific chromatin accessibility in L2 Caenorhabditis elegans nematodes.","date":"2021","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/33888511","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19860897","id":"PMC_19860897","title":"Role of L2 cysteines in papillomavirus infection and neutralization.","date":"2009","source":"Virology journal","url":"https://pubmed.ncbi.nlm.nih.gov/19860897","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17081983","id":"PMC_17081983","title":"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.","date":"2006","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/17081983","citation_count":2861,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22658674","id":"PMC_22658674","title":"Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22658674","citation_count":1718,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12477932","id":"PMC_12477932","title":"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12477932","citation_count":1479,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26186194","id":"PMC_26186194","title":"The BioPlex Network: A Systematic Exploration of the Human Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26496610","id":"PMC_26496610","title":"A human interactome in three quantitative dimensions organized by stoichiometries and abundances.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26496610","citation_count":1015,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32296183","id":"PMC_32296183","title":"A reference map of the human binary protein interactome.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32296183","citation_count":849,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29507755","id":"PMC_29507755","title":"VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.","date":"2018","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/29507755","citation_count":829,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"17353931","id":"PMC_17353931","title":"Large-scale mapping of human protein-protein interactions by mass spectrometry.","date":"2007","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/17353931","citation_count":733,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33961781","id":"PMC_33961781","title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33961781","citation_count":705,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21873635","id":"PMC_21873635","title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.","date":"2011","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/21873635","citation_count":656,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33060197","id":"PMC_33060197","title":"Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.","date":"2020","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/33060197","citation_count":564,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21423176","id":"PMC_21423176","title":"Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation.","date":"2011","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/21423176","citation_count":490,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15489334","id":"PMC_15489334","title":"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).","date":"2004","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/15489334","citation_count":438,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26638075","id":"PMC_26638075","title":"A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26638075","citation_count":433,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35271311","id":"PMC_35271311","title":"OpenCell: Endogenous tagging for the cartography of human cellular organization.","date":"2022","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/35271311","citation_count":432,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15324660","id":"PMC_15324660","title":"Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization.","date":"2004","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/15324660","citation_count":386,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"24255178","id":"PMC_24255178","title":"Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions.","date":"2013","source":"Science signaling","url":"https://pubmed.ncbi.nlm.nih.gov/24255178","citation_count":383,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34079125","id":"PMC_34079125","title":"A proximity-dependent biotinylation map of a human cell.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34079125","citation_count":339,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"9624153","id":"PMC_9624153","title":"Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins.","date":"1998","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9624153","citation_count":246,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"27173435","id":"PMC_27173435","title":"An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/27173435","citation_count":211,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29568061","id":"PMC_29568061","title":"An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29568061","citation_count":201,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15161933","id":"PMC_15161933","title":"Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15161933","citation_count":185,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32572027","id":"PMC_32572027","title":"Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32572027","citation_count":167,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25468996","id":"PMC_25468996","title":"E-cadherin interactome complexity and robustness resolved by quantitative proteomics.","date":"2014","source":"Science signaling","url":"https://pubmed.ncbi.nlm.nih.gov/25468996","citation_count":162,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30833792","id":"PMC_30833792","title":"A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape.","date":"2019","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30833792","citation_count":159,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15778465","id":"PMC_15778465","title":"Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer.","date":"2005","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/15778465","citation_count":153,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"24120883","id":"PMC_24120883","title":"CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor.","date":"2013","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/24120883","citation_count":152,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19322201","id":"PMC_19322201","title":"Ubiquitin-mediated proteolysis of HuR by heat shock.","date":"2009","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/19322201","citation_count":142,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"31871319","id":"PMC_31871319","title":"Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms.","date":"2019","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31871319","citation_count":137,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49665,"output_tokens":643,"usd":0.07932},"stage2":{"model":"claude-opus-4-6","input_tokens":3808,"output_tokens":1028,"usd":0.06711},"total_usd":0.357727,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":61755,"output_tokens":2702,"usd":0.112897},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5070,"output_tokens":1610,"usd":0.0984}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"PPFIBP1 acts as a fusion partner for ALK in inflammatory myofibroblastic tumor (IMT), forming a PPFIBP1-ALK fusion oncogene with transforming activity demonstrated by focus formation assay and in vivo tumorigenicity assay in 3T3 fibroblasts infected with a recombinant retrovirus encoding PPFIBP1-ALK.\",\n      \"method\": \"5'-RACE, RT-PCR, genomic PCR, FISH, focus formation assay, in vivo tumorigenicity assay\",\n      \"journal\": \"Clinical cancer research : an official journal of the American Association for Cancer Research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (RACE, PCR, FISH, functional transformation assays) in a single study with rigorous controls\",\n      \"pmids\": [\"21430068\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PPFIBP1 promotes glioma cell migration and invasion by activating the FAK/Src/JNK/c-Jun signaling axis and enhancing MMP-2 expression, likely through interaction with SRCIN1 (p140Cap); pharmacological inhibition of FAK and Src phosphorylation reversed the invasion enhancement caused by PPFIBP1 overexpression.\",\n      \"method\": \"Scratch assay, transwell invasion assay, xenograft mouse model, RNA-Seq/GO enrichment, Western blotting, co-immunoprecipitation (SRCIN1 interaction), pharmacological inhibition of FAK/Src\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KD/OE with defined cellular phenotype, pathway placement via pharmacological epistasis, and in vivo confirmation across multiple orthogonal methods in one study\",\n      \"pmids\": [\"34480020\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PPFIBP1 is a scaffold/adaptor protein that, when fused to ALK, generates a transforming oncogene in inflammatory myofibroblastic tumor; in its native context, PPFIBP1 promotes tumor cell migration and invasion by interacting with SRCIN1 (p140Cap) and activating the FAK/Src/JNK/c-Jun signaling pathway, leading to enhanced MMP-2 expression.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nLooking through the papers, I need to identify which ones are actually about PPFIBP1 (also known as liprin-β1, PPFIA binding protein 1).\n\n**Classification:**\n\n- Papers [1]-[5], [7], [10], [14], [19], [21]-[26], [29], [32], [39], [42], [44], [51], [56], [62], [67], [82], [85], [89], [91]-[93]: About PD-L1/PD-L2 (immune checkpoint) — EXCLUDE (alias collision: \"PD-L2\" ≠ PPFIBP1)\n- Papers [6], [8], [13], [20], [22], [28], [33], [36], [38], [41], [46], [52]-[53], [55], [58], [61], [66], [68], [81], [84], [88], [90], [94], [96]-[97], [100]: About papillomavirus L2 capsid protein — EXCLUDE\n- Papers [9], [11], [16], [35], [48], [77]: About bacterial L2 beta-lactamase — EXCLUDE\n- Paper [15], [17]: About cyclin L2 — EXCLUDE\n- Paper [18]: About Drosophila L2 cell line — EXCLUDE\n- Paper [30]: About GABARAP-L2 — EXCLUDE\n- Paper [31]: About L-2,3-diaminopropionic acid — EXCLUDE\n- Papers [34], [65]: About Chlamydia trachomatis L2 — EXCLUDE\n- Paper [37], [45], [78], [79], [87], [98]: About yeast GET pathway Sgt2/Get5 — EXCLUDE\n- Papers [40], [54], [69], [73]: About MICAL-L2 — EXCLUDE\n- Paper [43]: About Fasciola cathepsin L2 — EXCLUDE\n- Paper [47]: About Rad51 L1/L2 loops — EXCLUDE\n- Paper [49]: About Forkhead L2 (FOXL2) — EXCLUDE\n- Paper [50], [59], [72], [86]: About ribosomal protein L2 — EXCLUDE\n- Paper [57]: About apolipoprotein L2 — EXCLUDE\n- Paper [60], [71]: About tick sialostatin L2 — EXCLUDE\n- Paper [64]: About L2/HNK-1 carbohydrate — EXCLUDE\n- Paper [70]: About yeast ribosomal protein L2 — EXCLUDE\n- Paper [74]: About zebrafish Cxcl8-l2 — EXCLUDE\n- Paper [75]: About 20β-hydroxysteroid dehydrogenase — EXCLUDE\n- Paper [76]: About dental material cytotoxicity in L2 cells — EXCLUDE\n- Paper [80]: About geminivirus AL2/L2 — EXCLUDE (plant virus, symbol collision)\n- Paper [83]: About Leuconostoc lactis L2 EPS — EXCLUDE\n- Paper [95]: About TRPC3 L2 lipidation site — EXCLUDE\n- Paper [99]: About C. elegans L2 larvae — EXCLUDE\n\n**KEEP papers:**\n- Retrieved [24]: PPFIBP1-ALK fusion in IMT — KEEP\n- Retrieved [63]: PPFIBP1 in glioma via FAK/Src/JNK — KEEP\n\n**Additional curated papers:**\n- [20]: Liprins family, LAR phosphatase-interacting proteins — KEEP (foundational paper describing liprin/PPFIBP family)\n- [13]: Focal adhesion proteome, β-Pix — mentions PPFIBP1 in context — needs review. The abstract describes PPFIBP1 as part of focal adhesion proteome but no direct mechanistic finding about PPFIBP1 specifically.\n- [28]: KIF21A/KANK1/liprin — mentions liprin-α1/β1 in cortical microtubule complexes — KEEP (functional context for liprins including PPFIBP1/liprin-β1)\n- [1]-[12], [14]-[19], [21]-[27], [29]-[30]: Large proteomics/interactome screens — may contain PPFIBP1 as a detected protein but no specific mechanistic findings about it.\n- [30]: Rho GTPase proximity interactions — may mention PPFIBP1 but no specific mechanistic finding.\n\nLet me focus on papers with actual mechanistic findings about PPFIBP1:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"PPFIBP1 (liprin-β1) was identified as a member of the liprin family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. The C-terminal non-coiled-coil region of alpha-liprins binds to the membrane-distal phosphatase domains of LAR family members, and alpha-liprins also bind to the C-terminal non-coiled-coil region of beta-liprins (including PPFIBP1). Both alpha- and beta-liprins homodimerize via their N-terminal coiled-coil regions, establishing that liprins are multivalent proteins. Co-expression studies showed that liprin-alpha2 alters LAR cellular localization and induces LAR clustering, implicating liprins in localizing LAR family phosphatases at specific plasma membrane sites.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, co-expression localization studies, domain mapping\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal binding assays, domain mapping, and functional localization studies in a single foundational paper with multiple orthogonal methods\",\n      \"pmids\": [\"9624153\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PPFIBP1 (liprin-β1) was identified as a component of cortical microtubule attachment complexes. KIF21A is recruited to the cell cortex by KANK1, which co-clusters with liprin-α1/β1 and components of LL5β-containing complexes, placing liprin-β1 (PPFIBP1) within a multi-protein cortical complex that regulates microtubule growth at the cell periphery.\",\n      \"method\": \"Affinity proteomics, co-immunoprecipitation, confocal microscopy, functional rescue assays\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — co-IP and imaging place PPFIBP1 in the complex, but the direct functional role of PPFIBP1 specifically was not individually dissected\",\n      \"pmids\": [\"24120883\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PPFIBP1 was identified as part of the myosin-II-responsive focal adhesion proteome; its abundance in focal adhesions changes with myosin II activity, placing it within the contractility-regulated focal adhesion compartment.\",\n      \"method\": \"Quantitative proteomic analysis of isolated focal adhesions with and without myosin II inhibition (blebbistatin), mass spectrometry\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — PPFIBP1 detected in proteomics screen; no direct functional follow-up of PPFIBP1 specifically in this study\",\n      \"pmids\": [\"21423176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PPFIBP1 was identified as a novel ALK fusion partner (PPFIBP1-ALK) in pulmonary inflammatory myofibroblastic tumor (IMT). The PPFIBP1-ALK fusion was confirmed by 5'-RACE, RT-PCR, genomic PCR, and FISH. The fusion protein demonstrated transforming activity in NIH 3T3 fibroblasts in a focus formation assay and in an in vivo tumorigenicity assay using a recombinant retrovirus, establishing that PPFIBP1-ALK is an oncogenic fusion kinase.\",\n      \"method\": \"5'-RACE, RT-PCR, genomic PCR, FISH, focus formation assay, in vivo tumorigenicity assay in NIH 3T3 fibroblasts\",\n      \"journal\": \"Clinical cancer research : an official journal of the American Association for Cancer Research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — transforming activity confirmed by both in vitro focus formation and in vivo tumorigenicity assays with molecular confirmation by multiple methods\",\n      \"pmids\": [\"21430068\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PPFIBP1 promotes glioma cell migration and invasion through activation of the FAK/Src/JNK signaling pathway. Overexpression of PPFIBP1 activated FAK, Src, JNK, and c-Jun, enhancing MMP-2 expression, while knockdown inhibited invasion and migration in scratch and transwell assays. The mechanism involves interaction with SRCIN1 (p140Cap). Pharmacological inhibition of FAK and Src phosphorylation reversed the pro-invasive effects of PPFIBP1 overexpression. In xenograft models, PPFIBP1 overexpression facilitated tumor infiltration and reduced survival.\",\n      \"method\": \"Scratch assay, transwell invasion assay, RNA-seq, GO enrichment, Western blotting for pathway activation, pharmacological inhibition, xenograft mouse model, co-immunoprecipitation with SRCIN1\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods including KD/OE with defined phenotype, pathway identification, interacting partner identification, and in vivo validation\",\n      \"pmids\": [\"34480020\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PPFIBP1 (liprin-β1) is a multivalent scaffold protein that heterodimerizes with alpha-liprins and participates in localizing LAR-family receptor tyrosine phosphatases at the plasma membrane; it also forms part of cortical microtubule attachment complexes via KANK1, and in cancer cells activates FAK/Src/JNK/c-Jun signaling to promote invasion and MMP-2 expression through interaction with SRCIN1, while its N-terminal coiled-coil drives dimerization and its C-terminal domain mediates liprin-alpha binding.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PPFIBP1 is a scaffold/adaptor protein that promotes tumor cell migration and invasion by interacting with SRCIN1 (p140Cap) and activating the FAK/Src/JNK/c-Jun signaling axis, leading to enhanced MMP-2 expression; pharmacological inhibition of FAK and Src reverses PPFIBP1-driven invasion in glioma cells and xenograft models [PMID:34480020]. PPFIBP1 also serves as a fusion partner for ALK in inflammatory myofibroblastic tumor (IMT), where the PPFIBP1-ALK fusion oncogene exhibits transforming activity in focus formation and in vivo tumorigenicity assays [PMID:21430068].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Identification of PPFIBP1 as an ALK fusion partner in IMT established that the PPFIBP1 N-terminal region can mediate oligomerization-dependent activation of a receptor tyrosine kinase, implicating PPFIBP1 in oncogenic signaling.\",\n      \"evidence\": \"5'-RACE, RT-PCR, FISH, focus formation assay, and in vivo tumorigenicity assay in 3T3 fibroblasts expressing retroviral PPFIBP1-ALK\",\n      \"pmids\": [\"21430068\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The role of endogenous (non-fusion) PPFIBP1 in normal cell physiology was not addressed\",\n        \"The coiled-coil domain contribution to oligomerization was inferred but not directly mutagenized\",\n        \"No structural characterization of the fusion protein\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstration that PPFIBP1 drives glioma migration and invasion through the FAK/Src/JNK/c-Jun→MMP-2 pathway, with SRCIN1 as a direct interactor, defined a native signaling mechanism for PPFIBP1 independent of ALK fusion.\",\n      \"evidence\": \"Knockdown/overexpression in glioma cells, scratch and transwell assays, xenograft model, RNA-Seq, co-immunoprecipitation with SRCIN1, and pharmacological epistasis using FAK/Src inhibitors\",\n      \"pmids\": [\"34480020\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The PPFIBP1-SRCIN1 interaction was shown by co-IP but the binding domain and stoichiometry are undefined\",\n        \"Whether PPFIBP1 activates FAK/Src directly or indirectly through SRCIN1 relief-of-inhibition is unresolved\",\n        \"Function in non-transformed or non-neural cell types has not been characterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological function of PPFIBP1 in normal tissues, its full interactome beyond SRCIN1, and the structural basis of its scaffold activity remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function studies in non-cancer models or genetic organisms\",\n        \"No structural or domain-resolution mapping of PPFIBP1 scaffold interactions\",\n        \"Relationship between liprin-binding function and pro-invasive signaling is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SRCIN1\", \"ALK\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"PPFIBP1 (liprin-β1) is a multivalent scaffold protein that heterodimerizes with liprin-α family members through its C-terminal non-coiled-coil region and homodimerizes via its N-terminal coiled-coil domain, functioning to localize LAR-family receptor tyrosine phosphatases at specific plasma membrane sites [PMID:9624153]. It is a component of cortical microtubule attachment complexes containing KANK1, liprin-α1, and LL5β, linking it to regulation of microtubule dynamics at the cell periphery [PMID:24120883]. In glioma cells, PPFIBP1 promotes migration and invasion by interacting with SRCIN1 and activating FAK/Src/JNK/c-Jun signaling to upregulate MMP-2 expression, and its overexpression enhances tumor infiltration and reduces survival in xenograft models [PMID:34480020].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"The founding question of how LAR-family receptor phosphatases are localized at the plasma membrane was answered by identifying PPFIBP1 (liprin-β1) as a member of the liprin family that heterodimerizes with liprin-α proteins and participates in LAR clustering, establishing the multivalent scaffold model for phosphatase localization.\",\n      \"evidence\": \"Yeast two-hybrid, co-immunoprecipitation, domain mapping, and co-expression localization studies\",\n      \"pmids\": [\"9624153\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether liprin-β1 directly contacts LAR or only bridges via liprin-α remains unresolved\",\n        \"No structural data for the liprin-β1/liprin-α interface\",\n        \"Functional consequence of liprin-β1 loss on LAR signaling was not tested\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Placing PPFIBP1 within cortical microtubule attachment complexes containing KANK1, liprin-α1, and LL5β expanded its functional context from phosphatase scaffolding to regulation of microtubule capture at the cell periphery, while proteomic detection in focal adhesions linked it to the mechanosensitive adhesion compartment.\",\n      \"evidence\": \"Affinity proteomics, co-immunoprecipitation, confocal microscopy, and quantitative focal adhesion proteomics\",\n      \"pmids\": [\"24120883\", \"21423176\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific functional contribution of PPFIBP1 to cortical microtubule attachment was not individually dissected\",\n        \"Focal adhesion detection was proteomics-based without direct functional follow-up for PPFIBP1\",\n        \"Whether PPFIBP1's role in cortical complexes is independent of its LAR-scaffolding function is unknown\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identification of the PPFIBP1-ALK fusion in inflammatory myofibroblastic tumor demonstrated that the PPFIBP1 locus can serve as an oncogenic fusion partner, with the chimeric protein showing transforming activity both in vitro and in vivo.\",\n      \"evidence\": \"5'-RACE, RT-PCR, FISH confirmation, NIH 3T3 focus formation assay, and in vivo tumorigenicity assay\",\n      \"pmids\": [\"21430068\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the coiled-coil domain of PPFIBP1 drives constitutive dimerization of the fusion kinase was not tested\",\n        \"Prevalence of this fusion across tumor types beyond IMT is not established in this study\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The mechanism by which PPFIBP1 promotes cancer cell invasion was resolved: interaction with SRCIN1 activates FAK/Src/JNK/c-Jun signaling, upregulating MMP-2 and driving glioma cell migration, invasion, and in vivo tumor infiltration.\",\n      \"evidence\": \"Knockdown/overexpression, transwell and scratch assays, co-immunoprecipitation with SRCIN1, pharmacological pathway inhibition, and xenograft models in glioma cells\",\n      \"pmids\": [\"34480020\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the SRCIN1–FAK/Src axis operates in non-glioma contexts is untested\",\n        \"The structural basis of the PPFIBP1–SRCIN1 interaction is unknown\",\n        \"Relationship between the LAR-scaffolding and SRCIN1-mediated invasion functions has not been explored\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PPFIBP1's distinct interaction networks—LAR phosphatase scaffolding, cortical microtubule attachment, and SRCIN1-mediated invasion signaling—are coordinated or segregated in different cellular contexts remains an open question.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structure of PPFIBP1 or its complexes is available\",\n        \"Whether liprin-β1 has catalytic or enzymatic activity independent of scaffolding is unknown\",\n        \"Tissue-specific functions and knockout phenotypes in mammalian models are poorly characterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"Liprin-α/β complex\",\n      \"KANK1–liprin–LL5β cortical complex\"\n    ],\n    \"partners\": [\n      \"PPFIA1\",\n      \"PPFIA2\",\n      \"KANK1\",\n      \"SRCIN1\",\n      \"PTPRF\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}