{"gene":"EBP","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":2000,"finding":"Loss-of-function mutations in the EBP gene (encoding Δ8,Δ7 sterol isomerase / emopamil-binding protein) cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2); patients with nonsense EBP mutations displayed abnormal sterol profiles consistent with a defect in Δ8,Δ7 sterol isomerase activity, establishing EBP as the causative gene and confirming its enzymatic role in sterol biosynthesis.","method":"DNA sequencing of EBP in CDPX2 patients combined with sterol profile analysis (biochemical phenotyping) in patients with nonsense mutations","journal":"American journal of medical genetics","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function (patient mutations) with defined biochemical phenotype (sterol accumulation); single study but multiple patients and orthogonal genetic + biochemical methods","pmids":["11038443"],"is_preprint":false},{"year":2003,"finding":"CDPX2 (X-linked dominant chondrodysplasia punctata) can arise from somatic mosaicism for an EBP (sterol-Δ8-Δ7 isomerase) gene mutation, demonstrating that the EBP protein product is required cell-autonomously for normal skeletal and skin development and that mosaicism for loss of EBP function recapitulates the mosaic phenotype normally attributed to random X-inactivation in heterozygous females.","method":"Molecular genetic analysis (EBP sequencing) and biochemical sterol profiling in a mosaic male patient with CDPX2 clinical features","journal":"American journal of medical genetics. Part A","confidence":"Low","confidence_rationale":"Tier 3 — single case report with genetic and biochemical confirmation; mechanistic inference from mosaicism pattern rather than direct enzymatic assay","pmids":["12503102"],"is_preprint":false}],"current_model":"EBP encodes emopamil-binding protein, a Δ8,Δ7 sterol isomerase required for cholesterol biosynthesis; loss-of-function mutations cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2), with patient biochemical studies confirming that EBP deficiency leads to accumulation of Δ8-sterols consistent with its isomerase function in the sterol biosynthetic pathway."},"narrative":{"teleology":[{"year":2000,"claim":"Establishing EBP as the causative gene for CDPX2 resolved the molecular basis of this X-linked skeletal dysplasia and confirmed that the encoded protein functions as a Δ8,Δ7 sterol isomerase in vivo, as patient nonsense mutations produced sterol profiles diagnostic of blocked isomerase activity.","evidence":"EBP sequencing in multiple CDPX2 patients combined with biochemical sterol profiling","pmids":["11038443"],"confidence":"Medium","gaps":["No direct in vitro enzymatic reconstitution of human EBP isomerase activity was performed","Structural basis for substrate recognition and catalysis remains undefined","Genotype–phenotype correlation across the full mutation spectrum not established"]},{"year":2003,"claim":"Demonstrating that somatic mosaicism for an EBP mutation in a male recapitulates the mosaic CDPX2 phenotype established that EBP is required cell-autonomously, distinguishing mosaic loss of function from the random X-inactivation mechanism operative in heterozygous females.","evidence":"Molecular genetic and sterol profiling analysis of a single mosaic male CDPX2 patient","pmids":["12503102"],"confidence":"Low","gaps":["Single case report; not independently confirmed in additional mosaic individuals","Tissue-specific requirements for EBP in skeletal versus skin lineages not dissected","No functional rescue experiment performed"]},{"year":null,"claim":"The catalytic mechanism, three-dimensional structure, and complete genotype–phenotype landscape of EBP remain uncharacterized in the primary literature captured here; whether EBP has additional non-enzymatic roles (e.g., its original identification as an emopamil/sigma-ligand-binding protein) is unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal or cryo-EM structure available","No in vitro reconstitution of isomerase activity with purified human EBP","Pharmacological significance of emopamil binding versus isomerase activity not delineated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016853","term_label":"isomerase activity","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0]}],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"EBP encodes the Δ8,Δ7 sterol isomerase (emopamil-binding protein), an enzyme required for cholesterol biosynthesis that catalyzes the conversion of Δ8-sterols to Δ7-sterols. Loss-of-function mutations in EBP cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2), and patients carrying nonsense EBP mutations accumulate Δ8-sterols, confirming the enzymatic role of EBP in the sterol biosynthetic pathway [PMID:11038443]. Somatic mosaicism for EBP mutations recapitulates the mosaic phenotype of CDPX2, indicating that EBP function is required cell-autonomously for normal skeletal and skin development [PMID:12503102]."},"prefetch_data":{"uniprot":{"accession":"Q15125","full_name":"3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase","aliases":["Cholestenol Delta-isomerase","Cholesterol-5,6-epoxide hydrolase subunit EBP","Delta(8)-Delta(7) sterol isomerase","D8-D7 sterol isomerase","Emopamil-binding protein"],"length_aa":230,"mass_kda":26.4,"function":"Isomerase that catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers a catalytic step in the postlanosterol biosynthesis of cholesterol Component of the microsomal antiestrogen binding site (AEBS), a multiproteic complex at the ER membrane that consists of an association between EBP and 7-dehydrocholesterol reductase/DHCR7 (PubMed:15175332, PubMed:20615952). This complex is responsible for cholesterol-5,6-epoxide hydrolase (ChEH) activity, which consists in the hydration of cholesterol-5,6-epoxides (5,6-EC) into cholestane-3beta,5alpha,6beta-triol (CT) (PubMed:20615952). The precise role of each component of this complex has not been described yet (PubMed:20615952)","subcellular_location":"Endoplasmic reticulum membrane; Nucleus envelope; Cytoplasmic vesicle","url":"https://www.uniprot.org/uniprotkb/Q15125/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EBP","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000147155","cell_line_id":"CID000289","localizations":[{"compartment":"vesicles","grade":3},{"compartment":"er","grade":2}],"interactors":[{"gene":"DHCR24","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000289","total_profiled":1310},"omim":[{"mim_id":"621163","title":"ADIPOGENESIS REGULATORY FACTOR; ADIRF","url":"https://www.omim.org/entry/621163"},{"mim_id":"620787","title":"T-CELL ACTIVATION INHIBITOR, MITOCHONDRIAL; TCAIM","url":"https://www.omim.org/entry/620787"},{"mim_id":"620560","title":"CEBPA DIVERGENT TRANSCRIPT; CEBPA-DT","url":"https://www.omim.org/entry/620560"},{"mim_id":"619640","title":"LYSINE DEMETHYLASE 7A; KDM7A","url":"https://www.omim.org/entry/619640"},{"mim_id":"619246","title":"SPEXIN HORMONE; SPX","url":"https://www.omim.org/entry/619246"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear membrane","reliability":"Supported"},{"location":"Endoplasmic reticulum","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"liver","ntpm":307.1}],"url":"https://www.proteinatlas.org/search/EBP"},"hgnc":{"alias_symbol":["D8D7I","CPX","CPXD","CHO2"],"prev_symbol":["CDPX2"]},"alphafold":{"accession":"Q15125","domains":[{"cath_id":"-","chopping":"27-219","consensus_level":"high","plddt":97.9755,"start":27,"end":219}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15125","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15125-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15125-F1-predicted_aligned_error_v6.png","plddt_mean":95.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EBP","jax_strain_url":"https://www.jax.org/strain/search?query=EBP"},"sequence":{"accession":"Q15125","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15125.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15125/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15125"}},"corpus_meta":[{"pmid":"1840554","id":"PMC_1840554","title":"Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.","date":"1991","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/1840554","citation_count":1511,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2850264","id":"PMC_2850264","title":"Isolation of a recombinant copy of the gene encoding C/EBP.","date":"1988","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/2850264","citation_count":926,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18981473","id":"PMC_18981473","title":"PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale.","date":"2008","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/18981473","citation_count":688,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2494700","id":"PMC_2494700","title":"The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite.","date":"1989","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/2494700","citation_count":611,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8754828","id":"PMC_8754828","title":"Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153).","date":"1996","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8754828","citation_count":592,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7557387","id":"PMC_7557387","title":"Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis.","date":"1995","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/7557387","citation_count":456,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11830644","id":"PMC_11830644","title":"Surface sensing and adhesion of Escherichia coli controlled by the Cpx-signaling pathway.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11830644","citation_count":305,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1371993","id":"PMC_1371993","title":"Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response.","date":"1992","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1371993","citation_count":280,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9418879","id":"PMC_9418879","title":"The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation.","date":"1998","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9418879","citation_count":238,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15944395","id":"PMC_15944395","title":"Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors.","date":"2005","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15944395","citation_count":237,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9159399","id":"PMC_9159399","title":"The sigma(E) and the Cpx signal transduction systems control the synthesis of periplasmic protein-folding enzymes in Escherichia coli.","date":"1997","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/9159399","citation_count":225,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8530141","id":"PMC_8530141","title":"The C/EBP family of transcription factors.","date":"1995","source":"Immunobiology","url":"https://pubmed.ncbi.nlm.nih.gov/8530141","citation_count":220,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8756629","id":"PMC_8756629","title":"C/EBP, c-Myb, and PU.1 cooperate to regulate the neutrophil elastase promoter.","date":"1996","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8756629","citation_count":208,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2530632","id":"PMC_2530632","title":"Cognate DNA binding specificity retained after leucine zipper exchange between GCN4 and C/EBP.","date":"1989","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/2530632","citation_count":200,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10464196","id":"PMC_10464196","title":"The Cpx envelope stress response is controlled by amplification and feedback inhibition.","date":"1999","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/10464196","citation_count":195,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23160954","id":"PMC_23160954","title":"C/EBP transcription factors mediate epicardial activation during heart development and injury.","date":"2012","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/23160954","citation_count":188,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23665916","id":"PMC_23665916","title":"C/EBP maintains chromatin accessibility in liver and facilitates glucocorticoid receptor recruitment to steroid response elements.","date":"2013","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/23665916","citation_count":188,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19103922","id":"PMC_19103922","title":"Characterization of the Cpx regulon in Escherichia coli strain MC4100.","date":"2008","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/19103922","citation_count":181,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9199295","id":"PMC_9199295","title":"CREB controls LAP/C/EBP beta transcription.","date":"1997","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9199295","citation_count":175,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24184210","id":"PMC_24184210","title":"Everything old is new again: an update on current research on the Cpx envelope stress response.","date":"2013","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/24184210","citation_count":170,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29230213","id":"PMC_29230213","title":"Transcription Factor C/EBP Homologous Protein in Health and Diseases.","date":"2017","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/29230213","citation_count":164,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7929820","id":"PMC_7929820","title":"C/EBP beta regulation of the tumor necrosis factor alpha gene.","date":"1994","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/7929820","citation_count":161,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"14688407","id":"PMC_14688407","title":"Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/14688407","citation_count":157,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22092948","id":"PMC_22092948","title":"Just scratching the surface: an expanding view of the Cpx envelope stress response.","date":"2011","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/22092948","citation_count":154,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10322173","id":"PMC_10322173","title":"The sigmaE and Cpx regulatory pathways: overlapping but distinct envelope stress responses.","date":"1999","source":"Current opinion in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/10322173","citation_count":147,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3066687","id":"PMC_3066687","title":"Saccharomyces cerevisiae cho2 mutants are deficient in phospholipid methylation and cross-pathway regulation of inositol synthesis.","date":"1988","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/3066687","citation_count":145,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11353682","id":"PMC_11353682","title":"Altered expression of C/EBP family members results in decreased adipogenesis with aging.","date":"2001","source":"American journal of physiology. Regulatory, integrative and comparative physiology","url":"https://pubmed.ncbi.nlm.nih.gov/11353682","citation_count":145,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11792321","id":"PMC_11792321","title":"Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter.","date":"2002","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/11792321","citation_count":133,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15225623","id":"PMC_15225623","title":"A novel CPx-ATPase from the cadmium hyperaccumulator Thlaspi caerulescens.","date":"2004","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/15225623","citation_count":131,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15985538","id":"PMC_15985538","title":"Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia.","date":"2005","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/15985538","citation_count":127,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9032264","id":"PMC_9032264","title":"Cloning of the novel human myeloid-cell-specific C/EBP-epsilon transcription factor.","date":"1997","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9032264","citation_count":124,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16487683","id":"PMC_16487683","title":"The Cpx system of Escherichia coli, a strategic signaling pathway for confronting adverse conditions and for settling biofilm communities?","date":"2006","source":"Research in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16487683","citation_count":123,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1892816","id":"PMC_1892816","title":"DNA-induced increase in the alpha-helical content of C/EBP and GCN4.","date":"1991","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1892816","citation_count":114,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11239167","id":"PMC_11239167","title":"The role of C/EBP(epsilon) in the terminal stages of granulocyte differentiation.","date":"2001","source":"Stem cells (Dayton, Ohio)","url":"https://pubmed.ncbi.nlm.nih.gov/11239167","citation_count":110,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7501458","id":"PMC_7501458","title":"Ig/EBP (C/EBP gamma) is a transdominant negative inhibitor of C/EBP family transcriptional activators.","date":"1995","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/7501458","citation_count":108,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22092888","id":"PMC_22092888","title":"Signal integration by the Cpx-envelope stress system.","date":"2011","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/22092888","citation_count":104,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10319019","id":"PMC_10319019","title":"The C/EBP family of transcription factors in the liver and other organs.","date":"1998","source":"International journal of experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/10319019","citation_count":104,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10906322","id":"PMC_10906322","title":"C/EBP regulates hepatic transcription of 11beta -hydroxysteroid dehydrogenase type 1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid signaling pathways.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10906322","citation_count":102,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8758898","id":"PMC_8758898","title":"C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines.","date":"1996","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/8758898","citation_count":91,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21389327","id":"PMC_21389327","title":"IMiD immunomodulatory compounds block C/EBP{beta} translation through eIF4E down-regulation resulting in inhibition of MM.","date":"2011","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/21389327","citation_count":83,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12242300","id":"PMC_12242300","title":"Calreticulin interacts with C/EBPalpha and C/EBPbeta mRNAs and represses translation of C/EBP proteins.","date":"2002","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12242300","citation_count":81,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31534504","id":"PMC_31534504","title":"CPX Targeting DJ-1 Triggers ROS-induced Cell Death and Protective Autophagy in Colorectal Cancer.","date":"2019","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/31534504","citation_count":78,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11792653","id":"PMC_11792653","title":"C/EBP DNA-binding activity is upregulated by a glucocorticoid-dependent mechanism in septic muscle.","date":"2002","source":"American journal of physiology. Regulatory, integrative and comparative physiology","url":"https://pubmed.ncbi.nlm.nih.gov/11792653","citation_count":74,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25422305","id":"PMC_25422305","title":"The Cpx envelope stress response modifies peptidoglycan cross-linking via the L,D-transpeptidase LdtD and the novel protein YgaU.","date":"2014","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/25422305","citation_count":74,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1459454","id":"PMC_1459454","title":"Drosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development.","date":"1992","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/1459454","citation_count":68,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21666710","id":"PMC_21666710","title":"C/EBP-δ regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1α.","date":"2011","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/21666710","citation_count":67,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30135303","id":"PMC_30135303","title":"Localized hypoxia links ER stress to lung fibrosis through induction of C/EBP homologous protein.","date":"2018","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/30135303","citation_count":67,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18163952","id":"PMC_18163952","title":"The interferon signaling network and transcription factor C/EBP-beta.","date":"2007","source":"Cellular & molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18163952","citation_count":66,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24351550","id":"PMC_24351550","title":"C/EBP homologous protein drives pro-catabolic responses in chondrocytes.","date":"2013","source":"Arthritis research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/24351550","citation_count":62,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10845904","id":"PMC_10845904","title":"Sp1 and C/EBP are necessary to activate the lactoferrin gene promoter during myeloid differentiation.","date":"2000","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/10845904","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11980905","id":"PMC_11980905","title":"Regulation of CCAAT/enhancer-binding protein (C/EBP) activator proteins by heterodimerization with C/EBPgamma (Ig/EBP).","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11980905","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12692227","id":"PMC_12692227","title":"The Papillomavirus E2 protein binds to and synergizes with C/EBP factors involved in keratinocyte differentiation.","date":"2003","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/12692227","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18832658","id":"PMC_18832658","title":"Human C/EBP-epsilon activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation.","date":"2008","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/18832658","citation_count":58,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11038443","id":"PMC_11038443","title":"Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata.","date":"2000","source":"American journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11038443","citation_count":54,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30833359","id":"PMC_30833359","title":"The Lipoprotein NlpE Is a Cpx Sensor That Serves as a Sentinel for Protein Sorting and Folding Defects in the Escherichia coli Envelope.","date":"2019","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/30833359","citation_count":51,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11750126","id":"PMC_11750126","title":"Molecular cloning, genetic mapping, and expression analysis of four zebrafish c/ebp genes.","date":"2001","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/11750126","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11916518","id":"PMC_11916518","title":"C/EBP-beta, C/EBP-delta, PU.1, AML1 genes: mutational analysis in 381 samples of hematopoietic and solid malignancies.","date":"2002","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/11916518","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8680485","id":"PMC_8680485","title":"Control of adipocyte differentiation by CCAAT/enhancer binding protein alpha (C/EBP alpha).","date":"1996","source":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","url":"https://pubmed.ncbi.nlm.nih.gov/8680485","citation_count":48,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26118414","id":"PMC_26118414","title":"Endogenous prostaglandin E2 potentiates anti-inflammatory phenotype of macrophage through the CREB-C/EBP-β cascade.","date":"2015","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/26118414","citation_count":48,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12606546","id":"PMC_12606546","title":"Transcription cooperation by NFAT.C/EBP composite enhancer complex.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12606546","citation_count":48,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28854265","id":"PMC_28854265","title":"Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression.","date":"2017","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28854265","citation_count":46,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15710476","id":"PMC_15710476","title":"Cooperative interaction of C/EBP beta and Tat modulates MCP-1 gene transcription in astrocytes.","date":"2005","source":"Journal of neuroimmunology","url":"https://pubmed.ncbi.nlm.nih.gov/15710476","citation_count":46,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22242125","id":"PMC_22242125","title":"Stress-induced C/EBP homology protein (CHOP) represses MyoD transcription to delay myoblast differentiation.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22242125","citation_count":44,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11438745","id":"PMC_11438745","title":"C/EBP epsilon mediates myeloid differentiation and is regulated by the CCAAT displacement protein (CDP/cut).","date":"2001","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11438745","citation_count":44,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25766403","id":"PMC_25766403","title":"The role of C/EBP-β LIP in multidrug resistance.","date":"2015","source":"Journal of the National Cancer Institute","url":"https://pubmed.ncbi.nlm.nih.gov/25766403","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22776069","id":"PMC_22776069","title":"Inhibition of CD200R1 expression by C/EBP β in reactive microglial cells.","date":"2012","source":"Journal of neuroinflammation","url":"https://pubmed.ncbi.nlm.nih.gov/22776069","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10073577","id":"PMC_10073577","title":"Identification of mouse CPX-1, a novel member of the metallocarboxypeptidase gene family with highest similarity to CPX-2.","date":"1999","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/10073577","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8440378","id":"PMC_8440378","title":"Differential adrenergic regulation of C/EBP alpha and C/EBP beta in brown adipose tissue.","date":"1993","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/8440378","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32034145","id":"PMC_32034145","title":"C/EBPɑ is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32034145","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25368298","id":"PMC_25368298","title":"The Vibrio cholerae Cpx envelope stress response senses and mediates adaptation to low iron.","date":"2014","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/25368298","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24398327","id":"PMC_24398327","title":"miRNA-130a regulates C/EBP-ε expression during granulopoiesis.","date":"2014","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/24398327","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12503102","id":"PMC_12503102","title":"X-linked dominant chondrodysplasia punctata (CDPX2) caused by single gene mosaicism in a male.","date":"2003","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/12503102","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17620356","id":"PMC_17620356","title":"Influence of the Cpx extracytoplasmic-stress-responsive pathway on Yersinia sp.-eukaryotic cell contact.","date":"2007","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/17620356","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25246476","id":"PMC_25246476","title":"The Cpx envelope stress response regulates and is regulated by small noncoding RNAs.","date":"2014","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/25246476","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12970736","id":"PMC_12970736","title":"Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells.","date":"2003","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/12970736","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27239734","id":"PMC_27239734","title":"C/EBP homologous protein modulates liraglutide-mediated attenuation of non-alcoholic steatohepatitis.","date":"2016","source":"Laboratory investigation; a journal of technical methods and pathology","url":"https://pubmed.ncbi.nlm.nih.gov/27239734","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23881867","id":"PMC_23881867","title":"Reciprocal modulation of C/EBP-α and C/EBP-β by IL-13 in activated microglia prevents neuronal death.","date":"2013","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/23881867","citation_count":36,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15064728","id":"PMC_15064728","title":"Identification of murine and human XCP1 genes as C/EBP-epsilon-dependent members of FIZZ/Resistin gene family.","date":"2004","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/15064728","citation_count":35,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31909714","id":"PMC_31909714","title":"Roles of C/EBP class bZip proteins in the growth and cell competition of Rp ('Minute') mutants in Drosophila.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/31909714","citation_count":35,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23646198","id":"PMC_23646198","title":"Ablation of C/EBP homologous protein does not protect T17M RHO mice from retinal degeneration.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23646198","citation_count":35,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15519652","id":"PMC_15519652","title":"Suppression of C/EBP alpha expression in biliary cell differentiation from hepatoblasts during mouse liver development.","date":"2004","source":"Journal of hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/15519652","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19542291","id":"PMC_19542291","title":"Genetic analysis of activation of the Vibrio cholerae Cpx pathway.","date":"2009","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/19542291","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18166146","id":"PMC_18166146","title":"C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis.","date":"2007","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/18166146","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16220546","id":"PMC_16220546","title":"C/EBP homologous protein is necessary for normal osteoblastic function.","date":"2006","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16220546","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8314590","id":"PMC_8314590","title":"The human C/EBP delta (CRP3/CELF) gene: structure and chromosomal localization.","date":"1993","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8314590","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29748013","id":"PMC_29748013","title":"Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural mesothelioma.","date":"2018","source":"Lung cancer (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/29748013","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25314137","id":"PMC_25314137","title":"Mmu-miR-615-3p regulates lipoapoptosis by inhibiting C/EBP homologous protein.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25314137","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20829351","id":"PMC_20829351","title":"C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20829351","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29425932","id":"PMC_29425932","title":"Ablation of C/EBP homologous protein attenuates renal fibrosis after ureteral obstruction by reducing autophagy and microtubule disruption.","date":"2018","source":"Biochimica et biophysica acta. Molecular basis of disease","url":"https://pubmed.ncbi.nlm.nih.gov/29425932","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20487295","id":"PMC_20487295","title":"Involvement and necessity of the Cpx regulon in the event of aberrant beta-barrel outer membrane protein assembly.","date":"2010","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/20487295","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27927209","id":"PMC_27927209","title":"Coordinated inhibition of C/EBP by Tribbles in multiple tissues is essential for Caenorhabditis elegans development.","date":"2016","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/27927209","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8810039","id":"PMC_8810039","title":"Functional characterization of the repeated UASINO element in the promoters of the INO1 and CHO2 genes of yeast.","date":"1996","source":"Yeast (Chichester, England)","url":"https://pubmed.ncbi.nlm.nih.gov/8810039","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22396222","id":"PMC_22396222","title":"Artemisinic acid is a regulator of adipocyte differentiation and C/EBP δ expression.","date":"2012","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22396222","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36892778","id":"PMC_36892778","title":"Envelope-Stress Sensing Mechanism of Rcs and Cpx Signaling Pathways in Gram-Negative Bacteria.","date":"2023","source":"Journal of microbiology (Seoul, Korea)","url":"https://pubmed.ncbi.nlm.nih.gov/36892778","citation_count":27,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21308746","id":"PMC_21308746","title":"Role of C/EBP-β, p38 MAPK, and MKK6 in IL-1β-mediated C3 gene regulation in astrocytes.","date":"2011","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21308746","citation_count":27,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29884649","id":"PMC_29884649","title":"Impaired DNA demethylation of C/EBP sites causes premature aging.","date":"2018","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/29884649","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21600648","id":"PMC_21600648","title":"C/EBP-α and C/EBP-β-mediated adipogenesis of human mesenchymal stem cells (hMSCs) using PLGA nanoparticles complexed with poly(ethyleneimmine).","date":"2011","source":"Biomaterials","url":"https://pubmed.ncbi.nlm.nih.gov/21600648","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19222842","id":"PMC_19222842","title":"Cyclic regulation of transcription factor C/EBP beta in human endometrium.","date":"2009","source":"Reproductive biology and endocrinology : RB&E","url":"https://pubmed.ncbi.nlm.nih.gov/19222842","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38227935","id":"PMC_38227935","title":"CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis.","date":"2024","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/38227935","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27006448","id":"PMC_27006448","title":"Identification of carboxypeptidase X (CPX)-1 as a positive regulator of adipogenesis.","date":"2016","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/27006448","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"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":"16626397","id":"PMC_16626397","title":"Senescence-associated beta-galactosidase is lysosomal beta-galactosidase.","date":"2006","source":"Aging cell","url":"https://pubmed.ncbi.nlm.nih.gov/16626397","citation_count":1124,"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":"11927518","id":"PMC_11927518","title":"Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction.","date":"2002","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/11927518","citation_count":879,"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":"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":"19056867","id":"PMC_19056867","title":"Large-scale proteomics and phosphoproteomics of urinary exosomes.","date":"2008","source":"Journal of the American Society of Nephrology : JASN","url":"https://pubmed.ncbi.nlm.nih.gov/19056867","citation_count":607,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8125298","id":"PMC_8125298","title":"Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.","date":"1994","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/8125298","citation_count":492,"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":"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":"5647842","id":"PMC_5647842","title":"Generalized gangliosidosis: beta-galactosidase deficiency.","date":"1968","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/5647842","citation_count":421,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16344560","id":"PMC_16344560","title":"Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.","date":"2005","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/16344560","citation_count":409,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8670798","id":"PMC_8670798","title":"The human cytosolic molecular chaperones hsp90, hsp70 (hsc70) and hdj-1 have distinct roles in recognition of a non-native protein and protein refolding.","date":"1996","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/8670798","citation_count":357,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23042114","id":"PMC_23042114","title":"Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.","date":"2012","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23042114","citation_count":278,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21900206","id":"PMC_21900206","title":"A directed protein interaction network for investigating intracellular signal transduction.","date":"2011","source":"Science signaling","url":"https://pubmed.ncbi.nlm.nih.gov/21900206","citation_count":258,"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":"21988832","id":"PMC_21988832","title":"Toward an understanding of the protein interaction network of the human liver.","date":"2011","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/21988832","citation_count":207,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"18524657","id":"PMC_18524657","title":"GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects.","date":"2008","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/18524657","citation_count":194,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25544563","id":"PMC_25544563","title":"Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes.","date":"2014","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/25544563","citation_count":173,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33939265","id":"PMC_33939265","title":"Senescence-associated β-galactosidase reveals the abundance of senescent CD8+ T cells in aging humans.","date":"2021","source":"Aging cell","url":"https://pubmed.ncbi.nlm.nih.gov/33939265","citation_count":164,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8383699","id":"PMC_8383699","title":"The 67-kD elastin/laminin-binding protein is related to an enzymatically inactive, alternatively spliced form of beta-galactosidase.","date":"1993","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/8383699","citation_count":157,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"9497360","id":"PMC_9497360","title":"The 67-kDa enzymatically inactive alternatively spliced variant of beta-galactosidase is identical to the elastin/laminin-binding protein.","date":"1998","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9497360","citation_count":154,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23533145","id":"PMC_23533145","title":"In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.","date":"2013","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/23533145","citation_count":138,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"3922758","id":"PMC_3922758","title":"Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein.","date":"1985","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/3922758","citation_count":134,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16314420","id":"PMC_16314420","title":"Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16314420","citation_count":130,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23376485","id":"PMC_23376485","title":"Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.","date":"2013","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/23376485","citation_count":126,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":47851,"output_tokens":838,"usd":0.078062},"stage2":{"model":"claude-opus-4-6","input_tokens":3691,"output_tokens":875,"usd":0.060495},"total_usd":0.303289,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":60011,"output_tokens":1242,"usd":0.099332},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":4080,"output_tokens":928,"usd":0.0654}},"stage1_raw":"Looking at these abstracts, I need to identify which ones are about the human gene EBP (emopamil-binding protein, a sterol delta-8-delta-7 isomerase involved in cholesterol biosynthesis, mutations causing CDPX2). \n\nThe vast majority of papers are about C/EBP transcription factors (CCAAT/enhancer-binding proteins), which is a completely different gene family. Papers about bacterial Cpx two-component systems are also unrelated. I need to focus on papers that specifically discuss EBP as the sterol isomerase / emopamil-binding protein.\n\nReviewing carefully:\n- PMID 11038443 (Ikegawa et al., 2000): directly about EBP gene mutations causing CDPX2, mentions Delta(8),Delta(7) sterol isomerase function and abnormal sterol profiles in patients with nonsense mutations\n- PMID 12503102 (Aughton et al., 2003): about CDPX2 caused by mosaicism for sterol-delta(8)-delta(7) isomerase gene mutation\n\nThese are the only two papers genuinely about EBP (emopamil-binding protein/sterol isomerase). The rest are about C/EBP transcription factors or bacterial Cpx systems — completely different proteins.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"Loss-of-function mutations in EBP (encoding Delta(8),Delta(7) sterol isomerase/emopamil-binding protein) cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2); patients with nonsense mutations showed abnormal sterol profiles consistent with a defect in Delta(8),Delta(7) sterol isomerase activity, establishing EBP's enzymatic role in sterol biosynthesis.\",\n      \"method\": \"Sequencing of the EBP gene in CDP patients combined with biochemical sterol profiling of patient samples\",\n      \"journal\": \"American journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function with direct biochemical readout (sterol profiles), single study\",\n      \"pmids\": [\"11038443\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Somatic mosaicism for an EBP (sterol-delta(8)-delta(7) isomerase) gene mutation is sufficient to cause CDPX2 phenotype in a male, demonstrating that EBP function is required in a cell-autonomous, dosage-sensitive manner during skeletal development.\",\n      \"method\": \"Biochemical sterol analysis and molecular mutation detection in a mosaic male patient\",\n      \"journal\": \"American journal of medical genetics. Part A\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single case report with biochemical confirmation, no in vitro reconstitution\",\n      \"pmids\": [\"12503102\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EBP encodes a Delta(8)-Delta(7) sterol isomerase (emopamil-binding protein) that catalyzes an essential step in cholesterol biosynthesis; loss-of-function mutations abolish this enzymatic activity, causing accumulation of Delta(8)-sterols and the X-linked dominant skeletal dysplasia CDPX2.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI need to first classify each paper as KEEP (about the canonical EBP protein — emopamil-binding protein, the Δ8-Δ7 sterol isomerase encoded by the X-linked EBP gene causing CDPX2) or EXCLUDE (alias collisions with C/EBP family transcription factors, Cpx bacterial stress response, CPX drug, CPX-1 carboxypeptidase, GLB1/beta-galactosidase/EBP elastin-binding protein, or other unrelated proteins).\n\n**KEEP papers:**\n- PMID:11038443 — Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata (CDPX2) — canonical EBP (sterol isomerase)\n- PMID:12503102 — X-linked dominant CDPX2 caused by single gene mosaicism in a male — canonical EBP\n\n**EXCLUDE papers (alias collisions):**\n- Papers [1]-[27] in retrieved corpus (except PMID:11038443, 12503102): These are about C/EBP transcription factors, Cpx bacterial stress responses, CPX drugs, CPX-1 carboxypeptidase, or yeast CHO2 — not canonical EBP\n- Additional gene2pubmed papers: About GLB1/beta-galactosidase EBP (elastin-binding protein — different gene), interactome screens, MGC cDNA projects, senescence markers — not canonical EBP sterol isomerase\n\nThe two KEEP papers (PMID:11038443 and PMID:12503102) describe clinical/genetic findings (EBP mutations, abnormal sterol profiles) but do not contain direct mechanistic experiments about how the protein works at a biochemical level — they confirm that EBP mutations cause CDPX2 and show sterol profiles consistent with Δ8,Δ7 sterol isomerase defect, but the mechanistic characterization (enzyme activity, structure, etc.) is not in these papers.\n\nPMID:11038443 does note \"Patients with nonsense mutations showed abnormal sterol profiles consistent with a defect in Δ8,Δ7 sterol isomerase\" — this links EBP to its enzymatic function through a loss-of-function experiment (patient mutations → sterol accumulation), which qualifies as a low-tier mechanistic finding.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"Loss-of-function mutations in the EBP gene (encoding Δ8,Δ7 sterol isomerase / emopamil-binding protein) cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2); patients with nonsense EBP mutations displayed abnormal sterol profiles consistent with a defect in Δ8,Δ7 sterol isomerase activity, establishing EBP as the causative gene and confirming its enzymatic role in sterol biosynthesis.\",\n      \"method\": \"DNA sequencing of EBP in CDPX2 patients combined with sterol profile analysis (biochemical phenotyping) in patients with nonsense mutations\",\n      \"journal\": \"American journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function (patient mutations) with defined biochemical phenotype (sterol accumulation); single study but multiple patients and orthogonal genetic + biochemical methods\",\n      \"pmids\": [\"11038443\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"CDPX2 (X-linked dominant chondrodysplasia punctata) can arise from somatic mosaicism for an EBP (sterol-Δ8-Δ7 isomerase) gene mutation, demonstrating that the EBP protein product is required cell-autonomously for normal skeletal and skin development and that mosaicism for loss of EBP function recapitulates the mosaic phenotype normally attributed to random X-inactivation in heterozygous females.\",\n      \"method\": \"Molecular genetic analysis (EBP sequencing) and biochemical sterol profiling in a mosaic male patient with CDPX2 clinical features\",\n      \"journal\": \"American journal of medical genetics. Part A\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single case report with genetic and biochemical confirmation; mechanistic inference from mosaicism pattern rather than direct enzymatic assay\",\n      \"pmids\": [\"12503102\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EBP encodes emopamil-binding protein, a Δ8,Δ7 sterol isomerase required for cholesterol biosynthesis; loss-of-function mutations cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2), with patient biochemical studies confirming that EBP deficiency leads to accumulation of Δ8-sterols consistent with its isomerase function in the sterol biosynthetic pathway.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"EBP encodes the Δ(8)-Δ(7) sterol isomerase (emopamil-binding protein), which catalyzes the conversion of Δ(8)-sterols to Δ(7)-sterols during cholesterol biosynthesis; loss-of-function mutations lead to accumulation of abnormal Δ(8)-sterols and cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2) [PMID:11038443]. EBP function is dosage-sensitive and required in a cell-autonomous manner during skeletal development, as somatic mosaicism for EBP mutations is sufficient to produce the CDPX2 phenotype in males [PMID:12503102].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Identification of EBP as the gene mutated in CDPX2 established that the emopamil-binding protein functions as the Δ(8)-Δ(7) sterol isomerase in cholesterol biosynthesis, resolving the enzymatic basis of the disease.\",\n      \"evidence\": \"Sequencing of EBP in CDPX2 patients combined with sterol profiling showing Δ(8)-sterol accumulation\",\n      \"pmids\": [\"11038443\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Enzymatic activity not reconstituted with purified protein in vitro\",\n        \"No structural basis for how specific mutations abolish isomerase activity\",\n        \"Mechanism linking abnormal sterol profiles to skeletal defects not defined\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Discovery that somatic mosaicism for an EBP mutation causes CDPX2 in a male demonstrated that EBP function is dosage-sensitive and cell-autonomous during skeletal development.\",\n      \"evidence\": \"Biochemical sterol analysis and mutation detection in a mosaic male CDPX2 patient\",\n      \"pmids\": [\"12503102\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single case report without independent replication\",\n        \"Threshold of mutant cell burden required for phenotypic manifestation unknown\",\n        \"No functional rescue experiment to confirm causality of the mosaic mutation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural mechanism of Δ(8)-Δ(7) sterol isomerase catalysis by EBP, the cellular pathways linking sterol intermediates to skeletal patterning defects, and the precise genotype–phenotype relationships in CDPX2 remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No crystal or cryo-EM structure of human EBP\",\n        \"Downstream signaling pathways affected by Δ(8)-sterol accumulation not delineated\",\n        \"No systematic genotype–phenotype correlation across a large CDPX2 cohort\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016853\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"EBP encodes the Δ8,Δ7 sterol isomerase (emopamil-binding protein), an enzyme required for cholesterol biosynthesis that catalyzes the conversion of Δ8-sterols to Δ7-sterols. Loss-of-function mutations in EBP cause X-linked dominant chondrodysplasia punctata type 2 (CDPX2), and patients carrying nonsense EBP mutations accumulate Δ8-sterols, confirming the enzymatic role of EBP in the sterol biosynthetic pathway [PMID:11038443]. Somatic mosaicism for EBP mutations recapitulates the mosaic phenotype of CDPX2, indicating that EBP function is required cell-autonomously for normal skeletal and skin development [PMID:12503102].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing EBP as the causative gene for CDPX2 resolved the molecular basis of this X-linked skeletal dysplasia and confirmed that the encoded protein functions as a Δ8,Δ7 sterol isomerase in vivo, as patient nonsense mutations produced sterol profiles diagnostic of blocked isomerase activity.\",\n      \"evidence\": \"EBP sequencing in multiple CDPX2 patients combined with biochemical sterol profiling\",\n      \"pmids\": [\"11038443\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct in vitro enzymatic reconstitution of human EBP isomerase activity was performed\",\n        \"Structural basis for substrate recognition and catalysis remains undefined\",\n        \"Genotype–phenotype correlation across the full mutation spectrum not established\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrating that somatic mosaicism for an EBP mutation in a male recapitulates the mosaic CDPX2 phenotype established that EBP is required cell-autonomously, distinguishing mosaic loss of function from the random X-inactivation mechanism operative in heterozygous females.\",\n      \"evidence\": \"Molecular genetic and sterol profiling analysis of a single mosaic male CDPX2 patient\",\n      \"pmids\": [\"12503102\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single case report; not independently confirmed in additional mosaic individuals\",\n        \"Tissue-specific requirements for EBP in skeletal versus skin lineages not dissected\",\n        \"No functional rescue experiment performed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic mechanism, three-dimensional structure, and complete genotype–phenotype landscape of EBP remain uncharacterized in the primary literature captured here; whether EBP has additional non-enzymatic roles (e.g., its original identification as an emopamil/sigma-ligand-binding protein) is unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No crystal or cryo-EM structure available\",\n        \"No in vitro reconstitution of isomerase activity with purified human EBP\",\n        \"Pharmacological significance of emopamil binding versus isomerase activity not delineated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016853\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}