{"gene":"EMD","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2010,"finding":"Lentivirus-associated MAPK/ERK2 phosphorylates emerin (EMD) in primary non-dividing cells shortly after HIV-1 or FIV infection. This phosphorylation is dependent on virion-associated MAPK, and its inhibition reduces integration of proviral DNA into chromatin. Expression of a kinase-inactive MEK1 mutant in virus-producer cells impaired virus-induced EMD phosphorylation and reduced viral integration during subsequent infection, placing EMD phosphorylation downstream of virion-associated MAPK and upstream of nuclear integration of the pre-integration complex.","method":"Kinase inhibitor treatment, MEK1 kinase-inactive and constitutively active mutant expression in producer cells, measurement of EMD phosphorylation by Western blot, proviral DNA integration assay in primary non-dividing cells","journal":"The Journal of general virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal functional rescue with kinase mutants and two orthogonal readouts (phosphorylation + integration), single lab","pmids":["20463147"],"is_preprint":false},{"year":2014,"finding":"In the C16-ceramide autophagy pathway, C16-ceramide induces phosphorylation of emerin (EMD) on its LEM domain via PRKACA (protein kinase A catalytic subunit). Phosphorylated EMD then binds MAP1LC3B, leading to increased autophagosome formation in colon cancer cells, identifying EMD as an enhancer of autophagosome formation in this pathway.","method":"C16-ceramide treatment of colon cancer cells, phosphorylation analysis, co-immunoprecipitation/binding assay between phospho-EMD and MAP1LC3B, autophagosome quantification","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — co-IP/binding plus phosphorylation analysis with kinase identification, single lab, single study","pmids":["24819607"],"is_preprint":false},{"year":2007,"finding":"In a family carrying both a homozygous LMNA mutation (R298C) and a novel in-frame EMD deletion (delK37), genetic analysis established that: (1) the EMD deletion alone (X-linked dominant) was sufficient to cause cardiac disease; (2) both the hemizygous EMD and homozygous LMNA mutations together were necessary to produce the full Emery-Dreifuss muscular dystrophy phenotype; (3) emerin protein was present in reduced amounts in EMD-mutated cells; and (4) lamin A/C and emerin expression were most severely reduced in doubly-mutated fibroblasts, demonstrating synergistic interaction between emerin and lamin A/C.","method":"Genetic co-segregation analysis, protein expression analysis (Western blot/immunostaining) in patient fibroblasts, neurologic/cardiologic clinical assessment of 14 family members","journal":"Neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis in human family combined with protein expression analysis, multiple affected individuals, single study","pmids":["17536044"],"is_preprint":false},{"year":2005,"finding":"A nonsense mutation in exon 6 of the EMD (STA) gene causes loss of emerin and is associated with X-linked Emery-Dreifuss muscular dystrophy, manifesting predominantly as atrial cardiomyopathy and sudden cardiac death with conduction disturbances, with incomplete penetrance in female carriers, demonstrating that EMD gene mutations can cause a cardiac-predominant phenotype even with minimal skeletal myopathy.","method":"Genetic mutation analysis (sequencing of EMD/STA gene in two EDMD families), clinical and cardiologic phenotyping of 16 carriers","journal":"Circulation","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genotype-phenotype correlation in human families, no direct molecular mechanism experiment beyond mutation identification","pmids":["15967842"],"is_preprint":false},{"year":2014,"finding":"Whole exome sequencing identified a novel deletion mutation in EMD exon 1 (c.26_39delATACCGAGCTGACC) in a Chinese family, resulting in near-complete loss of emerin protein, causing severe dilated cardiomyopathy with only mild skeletal muscle involvement, broadening the phenotypic spectrum of EMD loss-of-function mutations.","method":"Whole exome sequencing, linkage analysis, protein expression analysis in patient samples","journal":"BMC medical genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — mutation identification with protein loss confirmed, no mechanistic dissection of how emerin loss causes cardiomyopathy","pmids":["24997722"],"is_preprint":false},{"year":2011,"finding":"Analysis of 18 probands identified novel and recurrent EMD mutations, with exon 2 identified as a mutational hotspot (nonrandom distribution of mutations), likely due to its high GC content (60%), providing insight into the mutational mechanism at the EMD locus.","method":"Sequencing of EMD gene in 255 referred patients, statistical analysis of exon distribution of mutations, GC content analysis","journal":"Journal of human genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — descriptive mutational analysis, mechanistic inference about hotspot based on GC content without direct experimental validation","pmids":["21697856"],"is_preprint":false}],"current_model":"Emerin (EMD) is an inner nuclear membrane LEM-domain protein that interacts with lamin A/C (synergistically required for normal nuclear envelope function); its phosphorylation by virion-associated MAPK/ERK2 facilitates HIV pre-integration complex nuclear integration, and its PRKACA-mediated phosphorylation on the LEM domain enables binding to MAP1LC3B to enhance autophagosome formation; loss-of-function mutations cause X-linked Emery-Dreifuss muscular dystrophy with predominantly cardiac (conduction defects, cardiomyopathy) and variable skeletal muscle phenotypes."},"narrative":{"mechanistic_narrative":"Emerin (EMD) is an inner nuclear membrane LEM-domain protein whose function is governed by phosphorylation and whose loss causes X-linked Emery-Dreifuss muscular dystrophy. Genetic epistasis in a family carrying both an EMD deletion and an LMNA mutation established that emerin acts synergistically with lamin A/C, with combined loss most severely depleting both proteins and producing the full dystrophy phenotype [PMID:17536044]. EMD function is regulated by phosphorylation in two distinct contexts: virion-associated MAPK/ERK2 phosphorylates emerin in non-dividing cells, an event positioned downstream of the kinase and upstream of nuclear integration of the HIV-1 pre-integration complex [PMID:20463147]; and PRKACA-mediated phosphorylation of the LEM domain, induced by C16-ceramide, enables emerin to bind MAP1LC3B and enhance autophagosome formation [PMID:24819607]. Loss-of-function EMD mutations cause a predominantly cardiac phenotype — conduction defects, atrial cardiomyopathy, and dilated cardiomyopathy — with variable skeletal muscle involvement [PMID:15967842, PMID:24997722]. The molecular basis by which emerin loss produces cardiac and muscle disease has not been dissected in the available corpus.","teleology":[{"year":2005,"claim":"Established that EMD loss-of-function can produce a cardiac-predominant disease, decoupling the cardiac phenotype from overt skeletal myopathy.","evidence":"Sequencing of an exon 6 nonsense mutation and cardiologic phenotyping across two EDMD families","pmids":["15967842"],"confidence":"Low","gaps":["Genotype-phenotype correlation only; no molecular mechanism linking emerin loss to atrial cardiomyopathy","Incomplete penetrance in female carriers unexplained"]},{"year":2007,"claim":"Demonstrated that emerin and lamin A/C interact synergistically, since combined EMD and LMNA mutations were needed for the full dystrophy phenotype and most severely depleted both proteins.","evidence":"Genetic co-segregation and protein expression analysis in patient fibroblasts from a family carrying both EMD delK37 and LMNA R298C","pmids":["17536044"],"confidence":"Medium","gaps":["Synergy inferred from human genetics and protein levels, not from a reconstituted physical interaction assay","Molecular consequence of the emerin–lamin interaction loss not defined"]},{"year":2010,"claim":"Placed emerin phosphorylation in the HIV infection pathway, showing virion-associated MAPK/ERK2 phosphorylates emerin to facilitate pre-integration complex nuclear integration.","evidence":"Kinase inhibitor treatment plus MEK1 kinase-inactive/constitutively-active mutant expression in producer cells, with EMD phosphorylation Western blot and proviral integration assay in primary non-dividing cells","pmids":["20463147"],"confidence":"Medium","gaps":["Single lab; how phospho-emerin mechanistically promotes integration not defined","Phosphorylation site(s) not mapped in this study"]},{"year":2014,"claim":"Identified a regulated, phosphorylation-dependent role for emerin in autophagy, linking LEM-domain phosphorylation to MAP1LC3B binding and autophagosome formation.","evidence":"C16-ceramide treatment of colon cancer cells, phospho-EMD/MAP1LC3B co-IP, PRKACA kinase identification, and autophagosome quantification","pmids":["24819607"],"confidence":"Medium","gaps":["Single lab, single study; reciprocal validation of the EMD–MAP1LC3B interaction not shown","Whether this autophagy role connects to muscle/cardiac pathology unknown"]},{"year":2014,"claim":"Broadened the EMD phenotypic spectrum by linking near-complete emerin loss to severe dilated cardiomyopathy with only mild skeletal involvement.","evidence":"Whole exome sequencing, linkage, and protein expression analysis of an exon 1 deletion in a Chinese family","pmids":["24997722"],"confidence":"Low","gaps":["No mechanistic dissection of how emerin loss causes cardiomyopathy","Modifiers explaining variable skeletal involvement not identified"]},{"year":null,"claim":"How emerin loss mechanistically produces cardiac conduction defects and cardiomyopathy, and how its phosphorylation-dependent roles relate to muscle pathology, remains unresolved.","evidence":"No timeline discovery connects the molecular activities of emerin to the disease mechanism","pmids":[],"confidence":"Low","gaps":["No structural or biochemical model of emerin function at the inner nuclear membrane in the corpus","Phosphorylation sites and their cross-pathway regulation not integrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2]}],"localization":[],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[1]}],"complexes":[],"partners":["LMNA","MAP1LC3B","PRKACA"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P50402","full_name":"Emerin","aliases":[],"length_aa":254,"mass_kda":29.0,"function":"Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells (PubMed:32923640). EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD","subcellular_location":"Nucleus inner membrane; Nucleus outer membrane","url":"https://www.uniprot.org/uniprotkb/P50402/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EMD","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DDOST","stoichiometry":10.0},{"gene":"RPN2","stoichiometry":10.0},{"gene":"CCDC47","stoichiometry":10.0},{"gene":"CANX","stoichiometry":4.0},{"gene":"RPN1","stoichiometry":4.0},{"gene":"TMED10","stoichiometry":4.0},{"gene":"VAPA","stoichiometry":4.0},{"gene":"CDS2","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2},{"gene":"SCAMP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/EMD","total_profiled":1310},"omim":[{"mim_id":"617719","title":"EPIPHYSEAL DYSPLASIA, MULTIPLE, 7; EDM7","url":"https://www.omim.org/entry/617719"},{"mim_id":"616496","title":"NUCLEAR ENVELOPE INTEGRAL MEMBRANE PROTEIN 1; NEMP1","url":"https://www.omim.org/entry/616496"},{"mim_id":"616312","title":"LEM DOMAIN-CONTAINING PROTEIN 2; LEMD2","url":"https://www.omim.org/entry/616312"},{"mim_id":"614512","title":"TORSIN 1A-INTERACTING PROTEIN 1; TOR1AIP1","url":"https://www.omim.org/entry/614512"},{"mim_id":"613569","title":"SAD1 AND UNC84 DOMAIN-CONTAINING PROTEIN 2; SUN2","url":"https://www.omim.org/entry/613569"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nuclear membrane","reliability":"Enhanced"},{"location":"Endoplasmic reticulum","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/EMD"},"hgnc":{"alias_symbol":["STA","LEMD5"],"prev_symbol":[]},"alphafold":{"accession":"P50402","domains":[{"cath_id":"1.10.720.40","chopping":"2-50","consensus_level":"medium","plddt":88.8545,"start":2,"end":50}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P50402","model_url":"https://alphafold.ebi.ac.uk/files/AF-P50402-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P50402-F1-predicted_aligned_error_v6.png","plddt_mean":60.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EMD","jax_strain_url":"https://www.jax.org/strain/search?query=EMD"},"sequence":{"accession":"P50402","fasta_url":"https://rest.uniprot.org/uniprotkb/P50402.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P50402/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P50402"}},"corpus_meta":[{"pmid":"8955395","id":"PMC_8955395","title":"FLO11, a yeast gene related to the STA genes, encodes a novel cell surface flocculin.","date":"1996","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/8955395","citation_count":168,"is_preprint":false},{"pmid":"17443352","id":"PMC_17443352","title":"Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro.","date":"2007","source":"Cell and tissue research","url":"https://pubmed.ncbi.nlm.nih.gov/17443352","citation_count":165,"is_preprint":false},{"pmid":"11920637","id":"PMC_11920637","title":"alpha v-Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin.","date":"2002","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/11920637","citation_count":159,"is_preprint":false},{"pmid":"22806877","id":"PMC_22806877","title":"Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer.","date":"2012","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/22806877","citation_count":141,"is_preprint":false},{"pmid":"16551859","id":"PMC_16551859","title":"A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group.","date":"2006","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/16551859","citation_count":134,"is_preprint":false},{"pmid":"15483010","id":"PMC_15483010","title":"Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients.","date":"2004","source":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/15483010","citation_count":117,"is_preprint":false},{"pmid":"23553846","id":"PMC_23553846","title":"EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors.","date":"2013","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/23553846","citation_count":115,"is_preprint":false},{"pmid":"17277694","id":"PMC_17277694","title":"Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice.","date":"2006","source":"Neurosurgery","url":"https://pubmed.ncbi.nlm.nih.gov/17277694","citation_count":111,"is_preprint":false},{"pmid":"21154128","id":"PMC_21154128","title":"STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer.","date":"2010","source":"Current opinion in investigational drugs (London, England : 2000)","url":"https://pubmed.ncbi.nlm.nih.gov/21154128","citation_count":109,"is_preprint":false},{"pmid":"17693653","id":"PMC_17693653","title":"Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors.","date":"2007","source":"Annals of oncology : official journal of the European Society for Medical Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/17693653","citation_count":107,"is_preprint":false},{"pmid":"7889287","id":"PMC_7889287","title":"A pharmacological profile of the novel, peripherally-selective kappa-opioid receptor agonist, EMD 61753.","date":"1994","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/7889287","citation_count":105,"is_preprint":false},{"pmid":"22996189","id":"PMC_22996189","title":"Hepatitis B virus polymerase impairs interferon-α-induced STA T activation through inhibition of importin-α5 and protein kinase C-δ.","date":"2013","source":"Hepatology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/22996189","citation_count":103,"is_preprint":false},{"pmid":"24757144","id":"PMC_24757144","title":"STA-21, a promising STAT-3 inhibitor that reciprocally regulates Th17 and Treg cells, inhibits osteoclastogenesis in mice and humans and alleviates autoimmune inflammation in an experimental model of rheumatoid arthritis.","date":"2014","source":"Arthritis & rheumatology (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/24757144","citation_count":97,"is_preprint":false},{"pmid":"16804392","id":"PMC_16804392","title":"A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease.","date":"2006","source":"Inflammatory bowel diseases","url":"https://pubmed.ncbi.nlm.nih.gov/16804392","citation_count":91,"is_preprint":false},{"pmid":"18657349","id":"PMC_18657349","title":"The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors.","date":"2008","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/18657349","citation_count":85,"is_preprint":false},{"pmid":"15872007","id":"PMC_15872007","title":"STa and cGMP stimulate CFTR translocation to the surface of villus enterocytes in rat jejunum and is regulated by protein kinase G.","date":"2005","source":"American journal of physiology. Cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/15872007","citation_count":84,"is_preprint":false},{"pmid":"9250001","id":"PMC_9250001","title":"Comparison of effects of uroguanylin, guanylin, and Escherichia coli heat-stable enterotoxin STa in mouse intestine and kidney: evidence that uroguanylin is an intestinal natriuretic hormone.","date":"1997","source":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","url":"https://pubmed.ncbi.nlm.nih.gov/9250001","citation_count":84,"is_preprint":false},{"pmid":"24145866","id":"PMC_24145866","title":"Separation of spermatogenic cell types using STA-PUT velocity sedimentation.","date":"2013","source":"Journal of visualized experiments : JoVE","url":"https://pubmed.ncbi.nlm.nih.gov/24145866","citation_count":83,"is_preprint":false},{"pmid":"16533873","id":"PMC_16533873","title":"A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC).","date":"2006","source":"Annals of oncology : official journal of the European Society for Medical Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/16533873","citation_count":83,"is_preprint":false},{"pmid":"12183683","id":"PMC_12183683","title":"Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist.","date":"2002","source":"The Journal of pharmacology and experimental therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/12183683","citation_count":77,"is_preprint":false},{"pmid":"25634318","id":"PMC_25634318","title":"Fractionation of human spermatogenic cells using STA-PUT gravity sedimentation and their miRNA profiling.","date":"2015","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/25634318","citation_count":76,"is_preprint":false},{"pmid":"10381799","id":"PMC_10381799","title":"Peripheral effects of the kappa-opioid agonist EMD 61753 on pain and inflammation in rats and humans.","date":"1999","source":"The Journal of pharmacology and experimental therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/10381799","citation_count":74,"is_preprint":false},{"pmid":"19858307","id":"PMC_19858307","title":"Genetic fusions of heat-labile (LT) and heat-stable (ST) toxoids of porcine enterotoxigenic Escherichia coli elicit neutralizing anti-LT and anti-STa antibodies.","date":"2009","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/19858307","citation_count":71,"is_preprint":false},{"pmid":"11459205","id":"PMC_11459205","title":"Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx.","date":"2001","source":"Cancer chemotherapy and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/11459205","citation_count":70,"is_preprint":false},{"pmid":"17053051","id":"PMC_17053051","title":"Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor.","date":"2006","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/17053051","citation_count":69,"is_preprint":false},{"pmid":"19544563","id":"PMC_19544563","title":"The novel HSP90 inhibitor STA-1474 exhibits biologic activity against osteosarcoma cell lines.","date":"2009","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/19544563","citation_count":66,"is_preprint":false},{"pmid":"8780725","id":"PMC_8780725","title":"The guanylin/STa receptor is expressed in crypts and apical epithelium throughout the mouse intestine.","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8780725","citation_count":57,"is_preprint":false},{"pmid":"15967842","id":"PMC_15967842","title":"High incidence of sudden cardiac death with conduction disturbances and atrial cardiomyopathy caused by a nonsense mutation in the STA gene.","date":"2005","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/15967842","citation_count":57,"is_preprint":false},{"pmid":"12753373","id":"PMC_12753373","title":"The effects of enamel matrix derivative (EMD) on osteoblastic cells in culture and bone regeneration in a rat skull defect.","date":"2003","source":"Journal of periodontal research","url":"https://pubmed.ncbi.nlm.nih.gov/12753373","citation_count":57,"is_preprint":false},{"pmid":"18191236","id":"PMC_18191236","title":"The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation.","date":"2007","source":"Behavioural brain research","url":"https://pubmed.ncbi.nlm.nih.gov/18191236","citation_count":56,"is_preprint":false},{"pmid":"27717524","id":"PMC_27717524","title":"STA-21, a STAT-3 inhibitor, attenuates the development and progression of inflammation in collagen antibody-induced arthritis.","date":"2016","source":"Immunobiology","url":"https://pubmed.ncbi.nlm.nih.gov/27717524","citation_count":56,"is_preprint":false},{"pmid":"15076141","id":"PMC_15076141","title":"Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKS-IL2): results of a phase I trial in patients with prostate cancer.","date":"2004","source":"Journal of immunotherapy (Hagerstown, Md. : 1997)","url":"https://pubmed.ncbi.nlm.nih.gov/15076141","citation_count":54,"is_preprint":false},{"pmid":"17536044","id":"PMC_17536044","title":"Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism?","date":"2007","source":"Neurology","url":"https://pubmed.ncbi.nlm.nih.gov/17536044","citation_count":51,"is_preprint":false},{"pmid":"2737161","id":"PMC_2737161","title":"Rapid effects of the flavonoid EMD 21388 on serum thyroid hormone binding and thyrotropin regulation in the rat.","date":"1989","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/2737161","citation_count":51,"is_preprint":false},{"pmid":"24894651","id":"PMC_24894651","title":"Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).","date":"2014","source":"Investigational new drugs","url":"https://pubmed.ncbi.nlm.nih.gov/24894651","citation_count":49,"is_preprint":false},{"pmid":"21499701","id":"PMC_21499701","title":"The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration.","date":"2011","source":"Psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/21499701","citation_count":47,"is_preprint":false},{"pmid":"1312972","id":"PMC_1312972","title":"Atriopeptins and Escherichia coli enterotoxin STa have different sites of action in mammalian intestine.","date":"1992","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/1312972","citation_count":43,"is_preprint":false},{"pmid":"15619109","id":"PMC_15619109","title":"Selective serotonin 5-HT2A receptor antagonist EMD 281014 improves delayed matching performance in young and aged rhesus monkeys.","date":"2004","source":"Psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15619109","citation_count":41,"is_preprint":false},{"pmid":"17059817","id":"PMC_17059817","title":"Effects of the serotonin 5-HT2A/2C receptor agonist DOI and of the selective 5-HT2A or 5-HT2C receptor antagonists EMD 281014 and SB-243213, respectively, on sleep and waking in the rat.","date":"2006","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/17059817","citation_count":40,"is_preprint":false},{"pmid":"26573435","id":"PMC_26573435","title":"Muscle imaging in muscle dystrophies produced by mutations in the EMD and LMNA genes.","date":"2015","source":"Neuromuscular disorders : NMD","url":"https://pubmed.ncbi.nlm.nih.gov/26573435","citation_count":40,"is_preprint":false},{"pmid":"27350142","id":"PMC_27350142","title":"Identification of new heat-stable (STa) enterotoxin allele variants produced by human enterotoxigenic Escherichia coli (ETEC).","date":"2016","source":"International journal of medical microbiology : IJMM","url":"https://pubmed.ncbi.nlm.nih.gov/27350142","citation_count":39,"is_preprint":false},{"pmid":"29969592","id":"PMC_29969592","title":"The highly selective 5-HT2A antagonist EMD-281,014 reduces dyskinesia and psychosis in the l-DOPA-treated parkinsonian marmoset.","date":"2018","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29969592","citation_count":38,"is_preprint":false},{"pmid":"21225299","id":"PMC_21225299","title":"Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro.","date":"2011","source":"Clinical oral investigations","url":"https://pubmed.ncbi.nlm.nih.gov/21225299","citation_count":36,"is_preprint":false},{"pmid":"22073242","id":"PMC_22073242","title":"Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22073242","citation_count":35,"is_preprint":false},{"pmid":"30211813","id":"PMC_30211813","title":"Results from phase II trial of HSP90 inhibitor, STA-9090 (ganetespib), in metastatic uveal melanoma.","date":"2018","source":"Melanoma research","url":"https://pubmed.ncbi.nlm.nih.gov/30211813","citation_count":35,"is_preprint":false},{"pmid":"10333165","id":"PMC_10333165","title":"Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial.","date":"1999","source":"Pharmacopsychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/10333165","citation_count":33,"is_preprint":false},{"pmid":"1360449","id":"PMC_1360449","title":"Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) and protein kinase C.","date":"1992","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/1360449","citation_count":33,"is_preprint":false},{"pmid":"11829064","id":"PMC_11829064","title":"Genotypic prevalence of the fimbrial adhesins (F4, F5, F6, F41 and F18) and toxins (LT, STa, STb and STx2e) in Escherichia coli isolated from postweaning pigs with diarrhoea or oedema disease in Korea.","date":"2002","source":"The Veterinary record","url":"https://pubmed.ncbi.nlm.nih.gov/11829064","citation_count":33,"is_preprint":false},{"pmid":"8982660","id":"PMC_8982660","title":"Neuropharmacological profile of EMD 57445, a sigma receptor ligand with potential antipsychotic activity.","date":"1996","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/8982660","citation_count":32,"is_preprint":false},{"pmid":"12236624","id":"PMC_12236624","title":"Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor: a human PET study with [11C]WAY-100635 and [11C]raclopride.","date":"2002","source":"Journal of psychopharmacology (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/12236624","citation_count":32,"is_preprint":false},{"pmid":"15507224","id":"PMC_15507224","title":"Prophylactic and therapeutic effects of acute systemic injections of EMD 281014, a selective serotonin 2A receptor antagonist on anxiety induced by predator stress in rats.","date":"2004","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15507224","citation_count":32,"is_preprint":false},{"pmid":"2752147","id":"PMC_2752147","title":"Molecular genetic analysis of a hybrid gene encoding Sta glycophorin of the human erythrocyte membrane.","date":"1989","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/2752147","citation_count":30,"is_preprint":false},{"pmid":"3275777","id":"PMC_3275777","title":"Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu psi[CH(OH)CH2]Val or leu psi[CH2NH]Val substitutions.","date":"1988","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/3275777","citation_count":30,"is_preprint":false},{"pmid":"29922268","id":"PMC_29922268","title":"Co-administered Tag-Less Toxoid Fusion 3xSTaN12S-mnLTR192G/L211A and CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) Induce Neutralizing Antibodies to 7 Adhesins (CFA/I, CS1-CS6) and Both Enterotoxins (LT, STa) of Enterotoxigenic Escherichia coli (ETEC).","date":"2018","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29922268","citation_count":29,"is_preprint":false},{"pmid":"7586281","id":"PMC_7586281","title":"Effects of EMD 57033 on contraction and relaxation in isolated rabbit hearts.","date":"1995","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/7586281","citation_count":29,"is_preprint":false},{"pmid":"23479455","id":"PMC_23479455","title":"The 5-hydroxytryptamine (serotonin) receptor 6 agonist EMD 386088 ameliorates ketamine-induced deficits in attentional set shifting and novel object recognition, but not in the prepulse inhibition in rats.","date":"2013","source":"Journal of psychopharmacology (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/23479455","citation_count":29,"is_preprint":false},{"pmid":"27608846","id":"PMC_27608846","title":"STA-8666, a novel HSP90 inhibitor/SN-38 drug conjugate, causes complete tumor regression in preclinical mouse models of pediatric sarcoma.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/27608846","citation_count":28,"is_preprint":false},{"pmid":"6257526","id":"PMC_6257526","title":"Increased benzodiazepine receptor number elicited in vitro by a novel purine, EMD 28422.","date":"1980","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/6257526","citation_count":28,"is_preprint":false},{"pmid":"21697856","id":"PMC_21697856","title":"Novel and recurrent EMD mutations in patients with Emery-Dreifuss muscular dystrophy, identify exon 2 as a mutation hot spot.","date":"2011","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21697856","citation_count":27,"is_preprint":false},{"pmid":"23294527","id":"PMC_23294527","title":"T-cell activation by treatment of cancer patients with EMD 521873 (Selectikine), an IL-2/anti-DNA fusion protein.","date":"2013","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23294527","citation_count":26,"is_preprint":false},{"pmid":"29263112","id":"PMC_29263112","title":"Enterotoxigenic Escherichia coli Adhesin-Toxoid Multiepitope Fusion Antigen CFA/I/II/IV-3xSTaN12S-mnLTG192G/L211A-Derived Antibodies Inhibit Adherence of Seven Adhesins, Neutralize Enterotoxicity of LT and STa Toxins, and Protect Piglets against Diarrhea.","date":"2018","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/29263112","citation_count":26,"is_preprint":false},{"pmid":"18096816","id":"PMC_18096816","title":"Heat-stable enterotoxin of Escherichia coli (STa) can stimulate duodenal HCO3(-) secretion via a novel GC-C- and CFTR-independent pathway.","date":"2007","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/18096816","citation_count":24,"is_preprint":false},{"pmid":"24997722","id":"PMC_24997722","title":"Whole exome sequencing identifies a novel EMD mutation in a Chinese family with dilated cardiomyopathy.","date":"2014","source":"BMC medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24997722","citation_count":23,"is_preprint":false},{"pmid":"24905144","id":"PMC_24905144","title":"Pharmacological evaluation of the anxiolytic-like effects of EMD 386088, a partial 5-HT6 receptor agonist, in the rat elevated plus-maze and Vogel conflict tests.","date":"2014","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/24905144","citation_count":23,"is_preprint":false},{"pmid":"21085949","id":"PMC_21085949","title":"Protection of mice against enterotoxigenic E. coli by immunization with a polyvalent enterotoxin comprising a combination of LTB, STa, and STb.","date":"2010","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/21085949","citation_count":22,"is_preprint":false},{"pmid":"19901280","id":"PMC_19901280","title":"Reference intervals and method optimization for variables reflecting hypocoagulatory and hypercoagulatory states in dogs using the STA Compact automated analyzer.","date":"2009","source":"Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/19901280","citation_count":21,"is_preprint":false},{"pmid":"18847496","id":"PMC_18847496","title":"Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis.","date":"2008","source":"Arthritis research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/18847496","citation_count":21,"is_preprint":false},{"pmid":"26976446","id":"PMC_26976446","title":"EMD in periodontal regenerative surgery modulates cytokine profiles: A randomised controlled clinical trial.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26976446","citation_count":20,"is_preprint":false},{"pmid":"8019761","id":"PMC_8019761","title":"Central and peripheral actions of the novel kappa-opioid receptor agonist, EMD 60400.","date":"1994","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/8019761","citation_count":19,"is_preprint":false},{"pmid":"15356479","id":"PMC_15356479","title":"Direct contact between enamel matrix derivative (EMD) and osteoblasts is not required for EMD-induced cell proliferation.","date":"2004","source":"Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics","url":"https://pubmed.ncbi.nlm.nih.gov/15356479","citation_count":19,"is_preprint":false},{"pmid":"1769524","id":"PMC_1769524","title":"A recombinant Escherichia coli heat-stable enterotoxin (STa) fusion protein eliciting anti-STa neutralizing antibodies.","date":"1991","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/1769524","citation_count":19,"is_preprint":false},{"pmid":"32308431","id":"PMC_32308431","title":"HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32308431","citation_count":19,"is_preprint":false},{"pmid":"26077660","id":"PMC_26077660","title":"Antidepressant-like activity of EMD 386088, a 5-HT6 receptor partial agonist, following systemic acute and chronic administration to rats.","date":"2015","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/26077660","citation_count":19,"is_preprint":false},{"pmid":"2671027","id":"PMC_2671027","title":"Identification of Escherichia coli that produces heat-stable enterotoxin STA by a commercially available enzyme-linked immunoassay and comparison of the assay with infant mouse and DNA probe tests.","date":"1989","source":"Journal of clinical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/2671027","citation_count":19,"is_preprint":false},{"pmid":"30298296","id":"PMC_30298296","title":"Effect of the selective 5-HT2A receptor antagonist EMD-281,014 on L-DOPA-induced abnormal involuntary movements in the 6-OHDA-lesioned rat.","date":"2018","source":"Experimental brain research","url":"https://pubmed.ncbi.nlm.nih.gov/30298296","citation_count":19,"is_preprint":false},{"pmid":"15371299","id":"PMC_15371299","title":"Interactions of the stereoisomers of alpha-hydroxytamoxifen with human hydroxysteroid sulfotransferase SULT2A1 and rat hydroxysteroid sulfotransferase STa.","date":"2004","source":"Drug metabolism and disposition: the biological fate of chemicals","url":"https://pubmed.ncbi.nlm.nih.gov/15371299","citation_count":19,"is_preprint":false},{"pmid":"12173026","id":"PMC_12173026","title":"Pathogenic mutations and rare variants of the APC gene identified in 75 Belgian patients with familial adenomatous polyposis by fluorescent enzymatic mutation detection (EMD).","date":"2002","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/12173026","citation_count":18,"is_preprint":false},{"pmid":"8552981","id":"PMC_8552981","title":"High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: implication of an alternatively spliced form containing the STA domain in CD46 up-regulation.","date":"1995","source":"Scandinavian journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/8552981","citation_count":18,"is_preprint":false},{"pmid":"20732355","id":"PMC_20732355","title":"Effects of the 5-HT₆ receptor antagonists SB-399885 and RO-4368554 and of the 5-HT(2A) receptor antagonist EMD 281014 on sleep and wakefulness in the rat during both phases of the light-dark cycle.","date":"2010","source":"Behavioural brain research","url":"https://pubmed.ncbi.nlm.nih.gov/20732355","citation_count":17,"is_preprint":false},{"pmid":"20463147","id":"PMC_20463147","title":"Lentivirus-associated MAPK/ERK2 phosphorylates EMD and regulates infectivity.","date":"2010","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/20463147","citation_count":16,"is_preprint":false},{"pmid":"3084921","id":"PMC_3084921","title":"Allelism within the DEX and STA gene families in Saccharomyces diastaticus.","date":"1986","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/3084921","citation_count":16,"is_preprint":false},{"pmid":"29079628","id":"PMC_29079628","title":"Neutralizing Anti-Heat-Stable Toxin (STa) Antibodies Derived from Enterotoxigenic Escherichia coli Toxoid Fusions with STa Proteins Containing N12S, L9A/N12S, or N12S/A14T Mutations Show Little Cross-Reactivity with Guanylin or Uroguanylin.","date":"2018","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29079628","citation_count":16,"is_preprint":false},{"pmid":"11155118","id":"PMC_11155118","title":"A reconsideration of the evidence for Escherichia coli STa (heat stable) enterotoxin-driven fluid secretion: a new view of STa action and a new paradigm for fluid absorption.","date":"2001","source":"Journal of applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11155118","citation_count":15,"is_preprint":false},{"pmid":"11682180","id":"PMC_11682180","title":"STa-induced translocation of protein kinase C from cytosol to membrane in rat enterocytes.","date":"2001","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/11682180","citation_count":15,"is_preprint":false},{"pmid":"11239925","id":"PMC_11239925","title":"Systemic EMD 68843 injections reduce anxiety in the shock-probe, but not the plus-maze test.","date":"2001","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/11239925","citation_count":15,"is_preprint":false},{"pmid":"24819607","id":"PMC_24819607","title":"New role for EMD (emerin), a key inner nuclear membrane protein, as an enhancer of autophagosome formation in the C16-ceramide autophagy pathway.","date":"2014","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/24819607","citation_count":14,"is_preprint":false},{"pmid":"15007535","id":"PMC_15007535","title":"EMD 281014, a specific and potent 5HT2 antagonist in humans: a dose-finding PET study.","date":"2004","source":"Psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15007535","citation_count":14,"is_preprint":false},{"pmid":"17828804","id":"PMC_17828804","title":"Downregulation of human colon carcinoma cell (COLO-205) proliferation through PKG-MAP kinase mediated signaling cascade by E. coli heat stable enterotoxin (STa), a potent anti-angiogenic and anti-metastatic molecule.","date":"2008","source":"Journal of applied toxicology : JAT","url":"https://pubmed.ncbi.nlm.nih.gov/17828804","citation_count":13,"is_preprint":false},{"pmid":"9566032","id":"PMC_9566032","title":"Effect of 1,3-di-o-tolylguanidine (DTG), rimcazole and EMD 57445, the sigma receptor ligands, in the forced swimming test.","date":"1997","source":"Polish journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/9566032","citation_count":13,"is_preprint":false},{"pmid":"37080068","id":"PMC_37080068","title":"STA-21, a small molecule STAT3 inhibitor, ameliorates experimental autoimmune encephalomyelitis by altering Th-17/Treg balance.","date":"2023","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/37080068","citation_count":12,"is_preprint":false},{"pmid":"29187713","id":"PMC_29187713","title":"Injury and mechanism of recombinant E. coli expressing STa on piglets colon.","date":"2017","source":"The Journal of veterinary medical science","url":"https://pubmed.ncbi.nlm.nih.gov/29187713","citation_count":12,"is_preprint":false},{"pmid":"18181050","id":"PMC_18181050","title":"Developments in epidermal growth factor receptor-targeting therapy for solid tumors: focus on matuzumab (EMD 72000).","date":"2008","source":"Cancer investigation","url":"https://pubmed.ncbi.nlm.nih.gov/18181050","citation_count":12,"is_preprint":false},{"pmid":"10874320","id":"PMC_10874320","title":"Enzymatic mutation detection (EMD) of novel mutations (R565X and R1523X) in the FBN1 gene of patients with Marfan syndrome using T4 endonuclease VII.","date":"2000","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/10874320","citation_count":12,"is_preprint":false},{"pmid":"1362045","id":"PMC_1362045","title":"Effect of age on activation of porcine intestinal guanylate cyclase and binding of Escherichia coli heat-stable enterotoxin (STa) to porcine intestinal cells and brush border membranes.","date":"1992","source":"American journal of veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/1362045","citation_count":12,"is_preprint":false},{"pmid":"2647524","id":"PMC_2647524","title":"Sta!le and transient expression of mouse submaxillary gland renin cDNA in AtT20 cells: proteolytic processing and secretory pathways.","date":"1989","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/2647524","citation_count":12,"is_preprint":false},{"pmid":"1682817","id":"PMC_1682817","title":"Neurochemical profile of EMD 45609 (carmoxirole), a dopamine DA2-receptor agonist.","date":"1991","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/1682817","citation_count":12,"is_preprint":false},{"pmid":"9690807","id":"PMC_9690807","title":"Assessment of activated protein C resistance using a new and rapid venom-based test: STA Staclot APC-R.","date":"1998","source":"Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis","url":"https://pubmed.ncbi.nlm.nih.gov/9690807","citation_count":12,"is_preprint":false},{"pmid":"34936832","id":"PMC_34936832","title":"Intradermally Administered Enterotoxigenic Escherichia coli Vaccine Candidate MecVax Induces Functional Serum Immunoglobulin G Antibodies against Seven Adhesins (CFA/I and CS1 through CS6) and Both Toxins (STa and LT).","date":"2021","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34936832","citation_count":11,"is_preprint":false},{"pmid":"33794753","id":"PMC_33794753","title":"Investigation of anticancer activities of STA-9090 (ganetespib) as a second generation HSP90 inhibitor in Saos-2 osteosarcoma cells.","date":"2021","source":"Journal of chemotherapy (Florence, Italy)","url":"https://pubmed.ncbi.nlm.nih.gov/33794753","citation_count":11,"is_preprint":false},{"pmid":"15855022","id":"PMC_15855022","title":"DNA vaccination for the priming of neutralizing antibodies against non-immunogenic STa enterotoxin from enterotoxigenic Escherichia coli.","date":"2005","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/15855022","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":59327,"output_tokens":2025,"usd":0.104178,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8596,"output_tokens":2144,"usd":0.04829,"stage2_stop_reason":"end_turn"},"total_usd":0.152468,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the 100 papers, I need to identify which ones are about the canonical human gene EMD (emerin, also known as STA/LEMD5), encoding the inner nuclear membrane protein emerin involved in Emery-Dreifuss muscular dystrophy.\n\nMost papers are clearly irrelevant:\n- Papers about EMD drugs (pharmaceutical compounds named EMD followed by numbers)\n- Papers about STA genes in yeast (glucoamylase)\n- Papers about STa (heat-stable enterotoxin of E. coli)\n- Papers about enamel matrix derivative (EMD)\n- Papers about various pharmacological agents\n\nThe relevant papers about the emerin protein (EMD gene) are:\n- PMID 15967842: STA gene mutation causing cardiac disease (STA = EMD alias)\n- PMID 17536044: EMD and LMNA mutations, digenic mechanism, emerin-lamin interaction\n- PMID 21697856: Novel EMD mutations\n- PMID 24997722: Novel EMD deletion causing dilated cardiomyopathy\n- PMID 26573435: Muscle imaging in EMD/LMNA mutations\n- PMID 20463147: Lentivirus-associated MAPK/ERK2 phosphorylates EMD\n- PMID 24819607: EMD role in autophagosome formation, C16-ceramide pathway\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"Lentivirus-associated MAPK/ERK2 phosphorylates emerin (EMD) in primary non-dividing cells shortly after HIV-1 or FIV infection. This phosphorylation is dependent on virion-associated MAPK, and its inhibition reduces integration of proviral DNA into chromatin. Expression of a kinase-inactive MEK1 mutant in virus-producer cells impaired virus-induced EMD phosphorylation and reduced viral integration during subsequent infection, placing EMD phosphorylation downstream of virion-associated MAPK and upstream of nuclear integration of the pre-integration complex.\",\n      \"method\": \"Kinase inhibitor treatment, MEK1 kinase-inactive and constitutively active mutant expression in producer cells, measurement of EMD phosphorylation by Western blot, proviral DNA integration assay in primary non-dividing cells\",\n      \"journal\": \"The Journal of general virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal functional rescue with kinase mutants and two orthogonal readouts (phosphorylation + integration), single lab\",\n      \"pmids\": [\"20463147\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In the C16-ceramide autophagy pathway, C16-ceramide induces phosphorylation of emerin (EMD) on its LEM domain via PRKACA (protein kinase A catalytic subunit). Phosphorylated EMD then binds MAP1LC3B, leading to increased autophagosome formation in colon cancer cells, identifying EMD as an enhancer of autophagosome formation in this pathway.\",\n      \"method\": \"C16-ceramide treatment of colon cancer cells, phosphorylation analysis, co-immunoprecipitation/binding assay between phospho-EMD and MAP1LC3B, autophagosome quantification\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — co-IP/binding plus phosphorylation analysis with kinase identification, single lab, single study\",\n      \"pmids\": [\"24819607\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"In a family carrying both a homozygous LMNA mutation (R298C) and a novel in-frame EMD deletion (delK37), genetic analysis established that: (1) the EMD deletion alone (X-linked dominant) was sufficient to cause cardiac disease; (2) both the hemizygous EMD and homozygous LMNA mutations together were necessary to produce the full Emery-Dreifuss muscular dystrophy phenotype; (3) emerin protein was present in reduced amounts in EMD-mutated cells; and (4) lamin A/C and emerin expression were most severely reduced in doubly-mutated fibroblasts, demonstrating synergistic interaction between emerin and lamin A/C.\",\n      \"method\": \"Genetic co-segregation analysis, protein expression analysis (Western blot/immunostaining) in patient fibroblasts, neurologic/cardiologic clinical assessment of 14 family members\",\n      \"journal\": \"Neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis in human family combined with protein expression analysis, multiple affected individuals, single study\",\n      \"pmids\": [\"17536044\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"A nonsense mutation in exon 6 of the EMD (STA) gene causes loss of emerin and is associated with X-linked Emery-Dreifuss muscular dystrophy, manifesting predominantly as atrial cardiomyopathy and sudden cardiac death with conduction disturbances, with incomplete penetrance in female carriers, demonstrating that EMD gene mutations can cause a cardiac-predominant phenotype even with minimal skeletal myopathy.\",\n      \"method\": \"Genetic mutation analysis (sequencing of EMD/STA gene in two EDMD families), clinical and cardiologic phenotyping of 16 carriers\",\n      \"journal\": \"Circulation\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genotype-phenotype correlation in human families, no direct molecular mechanism experiment beyond mutation identification\",\n      \"pmids\": [\"15967842\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Whole exome sequencing identified a novel deletion mutation in EMD exon 1 (c.26_39delATACCGAGCTGACC) in a Chinese family, resulting in near-complete loss of emerin protein, causing severe dilated cardiomyopathy with only mild skeletal muscle involvement, broadening the phenotypic spectrum of EMD loss-of-function mutations.\",\n      \"method\": \"Whole exome sequencing, linkage analysis, protein expression analysis in patient samples\",\n      \"journal\": \"BMC medical genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — mutation identification with protein loss confirmed, no mechanistic dissection of how emerin loss causes cardiomyopathy\",\n      \"pmids\": [\"24997722\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Analysis of 18 probands identified novel and recurrent EMD mutations, with exon 2 identified as a mutational hotspot (nonrandom distribution of mutations), likely due to its high GC content (60%), providing insight into the mutational mechanism at the EMD locus.\",\n      \"method\": \"Sequencing of EMD gene in 255 referred patients, statistical analysis of exon distribution of mutations, GC content analysis\",\n      \"journal\": \"Journal of human genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — descriptive mutational analysis, mechanistic inference about hotspot based on GC content without direct experimental validation\",\n      \"pmids\": [\"21697856\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Emerin (EMD) is an inner nuclear membrane LEM-domain protein that interacts with lamin A/C (synergistically required for normal nuclear envelope function); its phosphorylation by virion-associated MAPK/ERK2 facilitates HIV pre-integration complex nuclear integration, and its PRKACA-mediated phosphorylation on the LEM domain enables binding to MAP1LC3B to enhance autophagosome formation; loss-of-function mutations cause X-linked Emery-Dreifuss muscular dystrophy with predominantly cardiac (conduction defects, cardiomyopathy) and variable skeletal muscle phenotypes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Emerin (EMD) is an inner nuclear membrane LEM-domain protein whose function is governed by phosphorylation and whose loss causes X-linked Emery-Dreifuss muscular dystrophy. Genetic epistasis in a family carrying both an EMD deletion and an LMNA mutation established that emerin acts synergistically with lamin A/C, with combined loss most severely depleting both proteins and producing the full dystrophy phenotype [#2]. EMD function is regulated by phosphorylation in two distinct contexts: virion-associated MAPK/ERK2 phosphorylates emerin in non-dividing cells, an event positioned downstream of the kinase and upstream of nuclear integration of the HIV-1 pre-integration complex [#0]; and PRKACA-mediated phosphorylation of the LEM domain, induced by C16-ceramide, enables emerin to bind MAP1LC3B and enhance autophagosome formation [#1]. Loss-of-function EMD mutations cause a predominantly cardiac phenotype \\u2014 conduction defects, atrial cardiomyopathy, and dilated cardiomyopathy \\u2014 with variable skeletal muscle involvement [#3, #4]. The molecular basis by which emerin loss produces cardiac and muscle disease has not been dissected in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established that EMD loss-of-function can produce a cardiac-predominant disease, decoupling the cardiac phenotype from overt skeletal myopathy.\",\n      \"evidence\": \"Sequencing of an exon 6 nonsense mutation and cardiologic phenotyping across two EDMD families\",\n      \"pmids\": [\n        \"15967842\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Genotype-phenotype correlation only; no molecular mechanism linking emerin loss to atrial cardiomyopathy\",\n        \"Incomplete penetrance in female carriers unexplained\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstrated that emerin and lamin A/C interact synergistically, since combined EMD and LMNA mutations were needed for the full dystrophy phenotype and most severely depleted both proteins.\",\n      \"evidence\": \"Genetic co-segregation and protein expression analysis in patient fibroblasts from a family carrying both EMD delK37 and LMNA R298C\",\n      \"pmids\": [\n        \"17536044\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Synergy inferred from human genetics and protein levels, not from a reconstituted physical interaction assay\",\n        \"Molecular consequence of the emerin\\u2013lamin interaction loss not defined\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Placed emerin phosphorylation in the HIV infection pathway, showing virion-associated MAPK/ERK2 phosphorylates emerin to facilitate pre-integration complex nuclear integration.\",\n      \"evidence\": \"Kinase inhibitor treatment plus MEK1 kinase-inactive/constitutively-active mutant expression in producer cells, with EMD phosphorylation Western blot and proviral integration assay in primary non-dividing cells\",\n      \"pmids\": [\n        \"20463147\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab; how phospho-emerin mechanistically promotes integration not defined\",\n        \"Phosphorylation site(s) not mapped in this study\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified a regulated, phosphorylation-dependent role for emerin in autophagy, linking LEM-domain phosphorylation to MAP1LC3B binding and autophagosome formation.\",\n      \"evidence\": \"C16-ceramide treatment of colon cancer cells, phospho-EMD/MAP1LC3B co-IP, PRKACA kinase identification, and autophagosome quantification\",\n      \"pmids\": [\n        \"24819607\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single study; reciprocal validation of the EMD\\u2013MAP1LC3B interaction not shown\",\n        \"Whether this autophagy role connects to muscle/cardiac pathology unknown\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Broadened the EMD phenotypic spectrum by linking near-complete emerin loss to severe dilated cardiomyopathy with only mild skeletal involvement.\",\n      \"evidence\": \"Whole exome sequencing, linkage, and protein expression analysis of an exon 1 deletion in a Chinese family\",\n      \"pmids\": [\n        \"24997722\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No mechanistic dissection of how emerin loss causes cardiomyopathy\",\n        \"Modifiers explaining variable skeletal involvement not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How emerin loss mechanistically produces cardiac conduction defects and cardiomyopathy, and how its phosphorylation-dependent roles relate to muscle pathology, remains unresolved.\",\n      \"evidence\": \"No timeline discovery connects the molecular activities of emerin to the disease mechanism\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biochemical model of emerin function at the inner nuclear membrane in the corpus\",\n        \"Phosphorylation sites and their cross-pathway regulation not integrated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0060090\",\n        \"supporting_discovery_ids\": [\n          2\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-9612973\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"LMNA\",\n      \"MAP1LC3B\",\n      \"PRKACA\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":3,"faith_total":3,"faith_pct":100.0}}