{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:16:07Z","timestamp":1788491767729,"version":"build-2803163510"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100010665","name":"EU Framework Programme for Research and Innovation Marie Sklodowska-Curie Actions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001646","name":"Robert-Bosch Foundation GmbH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Archives of Biochemistry and Biophysics"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.abb.2021.108893","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T07:02:46Z","timestamp":1619506966000},"page":"108893","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Identification and characterization of novel splice variants of human farnesoid X receptor"],"prefix":"10.1016","volume":"705","author":[{"given":"Enni-Kaisa","family":"Mustonen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serene M.L.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno","family":"Nie\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatu","family":"Pantsar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-9656","authenticated-orcid":false,"given":"Oliver","family":"Burk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.abb.2021.108893_bib1","doi-asserted-by":"crossref","DOI":"10.1621\/nrs.08005","article-title":"Deciphering the nuclear bile acid receptor FXR paradigm","volume":"8","author":"Modica","year":"2010","journal-title":"Nucl. Recept. Signal."},{"key":"10.1016\/j.abb.2021.108893_bib2","doi-asserted-by":"crossref","first-page":"10638","DOI":"10.1074\/jbc.275.14.10638","article-title":"Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor","volume":"275","author":"Laffitte","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.abb.2021.108893_bib3","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1002\/hep.23450","article-title":"Genome-wide tissue-specific farnesoid X receptor binding in mouse liver and intestine","volume":"51","author":"Thomas","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.abb.2021.108893_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0105930","article-title":"Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes","volume":"9","author":"Zhan","year":"2014","journal-title":"PloS One"},{"key":"10.1016\/j.abb.2021.108893_bib5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0378-1119(02)00557-7","article-title":"Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters","volume":"290","author":"Huber","year":"2002","journal-title":"Gene"},{"key":"10.1016\/j.abb.2021.108893_bib6","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.bcp.2013.07.022","article-title":"Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition","volume":"86","author":"Vaquero","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.abb.2021.108893_bib7","doi-asserted-by":"crossref","first-page":"28857","DOI":"10.1074\/jbc.M011610200","article-title":"Human bile salt export pump promoter is transactivated by the farnesoid X receptor\/bile acid receptor","volume":"276","author":"Ananthanarayanan","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.abb.2021.108893_bib8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S1097-2765(00)00051-4","article-title":"A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis","volume":"6","author":"Goodwin","year":"2000","journal-title":"Mol. Cell."},{"key":"10.1016\/j.abb.2021.108893_bib9","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1161\/01.ATV.0000178994.21828.a7","article-title":"The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism","volume":"25","author":"Claudel","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.abb.2021.108893_bib10","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1053\/j.gastro.2017.01.014","article-title":"Receptor activation promotes hepatic amino acid catabolism and ammonium clearance in mice","volume":"152","author":"Massafra","year":"2017","journal-title":"Gastroenterology"},{"key":"10.1016\/j.abb.2021.108893_bib11","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.3390\/ijms19072069","article-title":"Update on FXR biology: promising therapeutic target?","volume":"19","author":"Han","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.abb.2021.108893_bib12","author":"FDA"},{"key":"10.1016\/j.abb.2021.108893_bib13","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0140-6736(14)61933-4","article-title":"Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial - the Lancet","volume":"2015","author":"Neuschwander-Tetri","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.abb.2021.108893_bib14","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial","volume":"394","author":"Younossi","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.abb.2021.108893_bib15","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.bbalip.2014.08.005","article-title":"Tissue-specific actions of FXR in metabolism and cancer","volume":"1851","author":"Gadaleta","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.abb.2021.108893_bib16","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.molmet.2015.09.005","article-title":"Bioenergetic cues shift FXR splicing towards FXR\u03b12 to modulate hepatic lipolysis and fatty acid metabolism","volume":"4","author":"Correia","year":"2015","journal-title":"Mol. Metab."},{"key":"10.1016\/j.abb.2021.108893_bib17","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.bcp.2017.04.013","article-title":"Ligand-dependent and -independent regulation of human hepatic sphingomyelin phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk with liver X receptor","volume":"136","author":"Jeske","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.abb.2021.108893_bib18","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1210\/me.2011-1235","article-title":"Evolutionary history and functional characterization of the amphibian xenosensor CAR","volume":"26","author":"Math\u00e4s","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.abb.2021.108893_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1478-1336-2-1","article-title":"Alternative splicing affects the function and tissue-specific expression of the human constitutive androstane receptor","volume":"2","author":"Arnold","year":"2004","journal-title":"Nucl. Recept."},{"key":"10.1016\/j.abb.2021.108893_bib20","doi-asserted-by":"crossref","first-page":"14581","DOI":"10.1074\/jbc.M010173200","article-title":"Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin","volume":"276","author":"Geick","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.abb.2021.108893_bib21","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1007\/s00204-017-1948-3","article-title":"Human pregnane X receptor is activated by dibenzazepine carbamate-based inhibitors of constitutive androstane receptor","volume":"91","author":"Jeske","year":"2017","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.abb.2021.108893_bib22","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1128\/AAC.04140-14","article-title":"Carboxymefloquine, the major metabolite of the antimalarial drug mefloquine, induces drug-metabolizing enzyme and transporter expression by activation of pregnane X receptor","volume":"59","author":"Piedade","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.abb.2021.108893_bib23","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1124\/dmd.106.013565","article-title":"Molecular mechanism of basal CYP3A4 regulation by hepatocyte nuclear factor 4\u03b1: evidence for direct regulation in the intestine","volume":"35","author":"Tegude","year":"2007","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.abb.2021.108893_bib24","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3: a force field providing broad coverage of drug-like small molecules and proteins","volume":"12","author":"Harder","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.abb.2021.108893_bib25","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1021\/acs.jctc.8b01026","article-title":"OPLS3e: extending Force Field Coverage for Drug-Like Small Molecules","volume":"15","author":"Roos","year":"2019","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.abb.2021.108893_bib26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10822-017-0088-4","article-title":"D3R Grand Challenge 2: blind prediction of protein\u2013ligand poses, affinity rankings, and relative binding free energies","volume":"32","author":"Gaieb","year":"2018","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.abb.2021.108893_bib27","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.abb.2021.108893_bib28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all\u2010atom protein loop prediction","volume":"2004","author":"Jacobson","year":"2004","journal-title":"Proteins"},{"key":"10.1016\/j.abb.2021.108893_bib29","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0022-2836(02)00470-9","article-title":"On the role of the crystal environment in determining protein side-chain conformations","volume":"320","author":"Jacobson","year":"2002","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.abb.2021.108893_bib30","series-title":"Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters","author":"Bowers","year":"2006"},{"key":"10.1016\/j.abb.2021.108893_bib31","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.abb.2021.108893_bib32","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1747-0285.2007.00483.x","article-title":"New method for fast and accurate binding-site identification and analysis","volume":"69","author":"Halgren","year":"2007","journal-title":"Chem. Biol. Drug Des."},{"key":"10.1016\/j.abb.2021.108893_bib33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1021\/ci800324m","article-title":"Identifying and characterizing binding sites and assessing druggability","volume":"49","author":"Halgren","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.abb.2021.108893_bib34","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1194\/jlr.M038323","article-title":"Mechanistic insights into isoform-dependent and species-specific regulation of bile salt export pump by farnesoid X receptor","volume":"54","author":"Song","year":"2013","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.abb.2021.108893_bib35","doi-asserted-by":"crossref","first-page":"19513","DOI":"10.1016\/S0021-9258(18)41805-4","article-title":"Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation","volume":"267","author":"Allan","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.abb.2021.108893_bib36","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bib\/bby047","article-title":"Exploring the functional impact of alternative splicing on human protein isoforms using available annotation sources","volume":"20","author":"Sulakhe","year":"2019","journal-title":"Briefings Bioinf."},{"key":"10.1016\/j.abb.2021.108893_bib37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1124\/dmd.119.089102","article-title":"Alternative splicing in the nuclear receptor superfamily expands gene function to refine endo-xenobiotic metabolism","volume":"48","author":"Annalora","year":"2020","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.abb.2021.108893_bib38","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1124\/mol.111.077206","article-title":"Differential expression and function of alternative splicing variants of human liver X receptor \u03b1","volume":"81","author":"Endo-Umeda","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.abb.2021.108893_bib39","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/nrm3454","article-title":"NMD: a multifaceted response to premature translational termination","volume":"13","author":"Kervestin","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.abb.2021.108893_bib40","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1053\/j.gastro.2020.07.036","article-title":"FXR isoforms control different metabolic functions in liver cells via binding to specific DNA motifs","volume":"159","author":"Ramos Pittol","year":"2020","journal-title":"Gastroenterology"},{"key":"10.1016\/j.abb.2021.108893_bib41","doi-asserted-by":"crossref","first-page":"486","DOI":"10.2174\/156802612799436641","article-title":"General molecular biology and architecture of nuclear receptors","volume":"12","author":"Pawlak","year":"2012","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.abb.2021.108893_bib42","doi-asserted-by":"crossref","first-page":"26517","DOI":"10.1074\/jbc.M502716200","article-title":"A novel peroxisome proliferator-activated receptor gamma isoform with dominant negative activity generated by alternative splicing","volume":"280","author":"Sabatino","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.abb.2021.108893_bib43","doi-asserted-by":"crossref","first-page":"G48","DOI":"10.1152\/ajpgi.00234.2013","article-title":"FXR silencing in human colon cancer by DNA methylation and KRAS signaling","volume":"306","author":"Bailey","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.abb.2021.108893_bib44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0043044","article-title":"FXR controls the tumor suppressor NDRG2 and FXR agonists reduce liver tumor growth and metastasis in an orthotopic mouse xenograft model","volume":"7","author":"Deuschle","year":"2012","journal-title":"PloS One"},{"key":"10.1016\/j.abb.2021.108893_bib45","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s12072-010-9202-6","article-title":"Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease","volume":"4","author":"Yang","year":"2010","journal-title":"Hepatol. Int."},{"key":"10.1016\/j.abb.2021.108893_bib46","doi-asserted-by":"crossref","first-page":"18180","DOI":"10.1074\/jbc.RA118.004652","article-title":"Ligand binding and heterodimerization with retinoid X receptor \u03b1 (RXR\u03b1) induce farnesoid X receptor (FXR) conformational changes affecting coactivator binding","volume":"293","author":"Wang","year":"2018","journal-title":"J. Biol. Chem."}],"container-title":["Archives of Biochemistry and Biophysics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003986121001430?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003986121001430?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T06:18:24Z","timestamp":1757744304000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003986121001430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":46,"alternative-id":["S0003986121001430"],"URL":"https:\/\/doi.org\/10.1016\/j.abb.2021.108893","relation":{},"ISSN":["0003-9861"],"issn-type":[{"value":"0003-9861","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification and characterization of novel splice variants of human farnesoid X receptor","name":"articletitle","label":"Article Title"},{"value":"Archives of Biochemistry and Biophysics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.abb.2021.108893","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108893"}}