{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:51:10Z","timestamp":1781941870419,"version":"3.54.5"},"reference-count":41,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100009555","name":"Henan Normal University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009555","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974321"],"award-info":[{"award-number":["81974321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.jtha.2025.12.006","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:15:55Z","timestamp":1765844155000},"page":"1279-1290","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining the critical roles of factor VIII residues 1900 to 1908 in factor VIIIa\u2013factor IXa complex formation and factor VIIIa activity"],"prefix":"10.1016","volume":"24","author":[{"given":"Haixia","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Ming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4495-3536","authenticated-orcid":false,"given":"Wensheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtha.2025.12.006_bib1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.18388\/abp.2015_1056","article-title":"The factor VIII protein and its function","volume":"63","author":"Mazurkiewicz-Pisarek","year":"2016","journal-title":"Acta Biochim Pol"},{"key":"10.1016\/j.jtha.2025.12.006_bib2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1182\/blood-2018-08-872291","article-title":"New therapies for hemophilia","volume":"133","author":"Weyand","year":"2019","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2025.12.006_bib3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.blre.2004.02.003","article-title":"Mutating factor VIII: lessons from structure to function","volume":"19","author":"Fay","year":"2005","journal-title":"Blood Rev"},{"key":"10.1016\/j.jtha.2025.12.006_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.thromres.2005.12.015","article-title":"The protein structure and effect of factor VIII","volume":"119","author":"Fang","year":"2007","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2025.12.006_bib5","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1111\/j.1538-7836.2005.01527.x","article-title":"Molecular models of the procoagulant factor VIIIa-factor IXa complex","volume":"3","author":"Autin","year":"2005","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2025.12.006_bib6","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1182\/blood-2001-12-0361","article-title":"Mutations associated with hemophilia A in the 558-565 loop of the factor VIIIa A2 subunit alter the catalytic activity of the factor Xase complex","volume":"100","author":"Jenkins","year":"2002","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2025.12.006_bib7","doi-asserted-by":"crossref","first-page":"15057","DOI":"10.1074\/jbc.M113.456467","article-title":"Factor VIIIa A2 subunit shows a high affinity interaction with factor IXa","volume":"288","author":"Griffiths","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib8","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1074\/jbc.M804955200","article-title":"The factor VIIIa C2 domain (residues 2228-2240) interacts with the factor IXa Gla domain in the factor Xase complex","volume":"284","author":"Soeda","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib9","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1160\/TH11-03-0203","article-title":"Interactions between residues 2228-2240 within factor VIIIa C2 domain and factor IXa Gla domain contribute to propagation of clot formation","volume":"106","author":"Soeda","year":"2011","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2025.12.006_bib10","doi-asserted-by":"crossref","first-page":"31289","DOI":"10.1074\/jbc.M113.497289","article-title":"Replacing the factor VIII C1 domain with a second C2 domain reduces factor VIII stability and affinity for factor IXa","volume":"288","author":"Wakabayashi","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib11","doi-asserted-by":"crossref","first-page":"7150","DOI":"10.1016\/S0021-9258(17)37260-5","article-title":"Identification of a binding site for blood coagulation factor IXa on the light chain of human factor VIII","volume":"269","author":"Lenting","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib12","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1074\/jbc.271.4.1935","article-title":"The sequence Glu1811-Lys1818 of human blood coagulation factor VIII comprises a binding site for activated factor IX","volume":"271","author":"Lenting","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib13","doi-asserted-by":"crossref","first-page":"26105","DOI":"10.1074\/jbc.M113.500884","article-title":"A3 domain region 1803-1818 contributes to the stability of activated factor VIII and includes a binding site for activated factor IX","volume":"288","author":"Bloem","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib14","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1111\/j.1538-7836.2011.04397.x","article-title":"Use of affinity-directed liquid chromatography-mass spectrometry to map the epitopes of a factor VIII inhibitor antibody fraction","volume":"9","author":"Griffiths","year":"2011","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2025.12.006_bib15","doi-asserted-by":"crossref","first-page":"15763","DOI":"10.1074\/jbc.M400568200","article-title":"Identification of a factor Xa-interactive site within residues 337-372 of the factor VIII heavy chain","volume":"279","author":"Nogami","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib16","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1021\/bi00507a028","article-title":"Phospholipid vesicle formation and transmembrane protein incorporation using octyl glucoside","volume":"20","author":"Mimms","year":"1981","journal-title":"Biochemistry"},{"issue":"Database issue","key":"10.1016\/j.jtha.2025.12.006_bib17","doi-asserted-by":"crossref","first-page":"D285","DOI":"10.1093\/nar\/gkt1180","article-title":"PDBe: Protein Data Bank in Europe","volume":"42","author":"Gutmanas","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jtha.2025.12.006_bib18","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1016\/j.jmb.2014.04.026","article-title":"SuSPect: enhanced prediction of single amino acid variant (SAV) phenotype using network features","volume":"426","author":"Yates","year":"2014","journal-title":"J Mol Biol"},{"key":"10.1016\/j.jtha.2025.12.006_bib19","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat Protoc"},{"key":"10.1016\/j.jtha.2025.12.006_bib20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/jth.14621","article-title":"The 3.2 A structure of a bioengineered variant of blood coagulation factor VIII indicates two conformations of the C2 domain","volume":"18","author":"Smith","year":"2020","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2025.12.006_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0024657","article-title":"Accelerating protein docking in ZDOCK using an advanced 3D convolution library","volume":"6","author":"Pierce","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2025.12.006_bib22","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/978-1-4939-6740-7_16","article-title":"Bioinformatics tools and resources for analyzing protein structures","volume":"1549","author":"Paxman","year":"2017","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.jtha.2025.12.006_bib23","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J Chem Inf Model"},{"key":"10.1016\/j.jtha.2025.12.006_bib24","doi-asserted-by":"crossref","first-page":"32248","DOI":"10.1074\/jbc.M109.050781","article-title":"Identification of residues in the 558-loop of factor VIIIa A2 subunit that interact with factor IXa","volume":"284","author":"Jagannathan","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib25","doi-asserted-by":"crossref","first-page":"27087","DOI":"10.1074\/jbc.270.45.27087","article-title":"Localization of factor IXa and factor VIIIa interactive sites","volume":"270","author":"O'Brien","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib26","doi-asserted-by":"crossref","first-page":"14005","DOI":"10.1016\/S0021-9258(18)71633-5","article-title":"Intersubunit fluorescence energy transfer in human factor VIII","volume":"264","author":"Fay","year":"1989","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib27","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1182\/blood-2008-02-142158","article-title":"Generation of enhanced stability factor VIII variants by replacement of charged residues at the A2 domain interface","volume":"112","author":"Wakabayashi","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2025.12.006_bib28","doi-asserted-by":"crossref","first-page":"8546","DOI":"10.1074\/jbc.270.15.8546","article-title":"Cleavage of factor VIII light chain is required for maximal generation of factor VIIIa activity","volume":"270","author":"Regan","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib29","doi-asserted-by":"crossref","first-page":"8850","DOI":"10.1021\/bi050145o","article-title":"Factor VIII A3 domain residues 1954-1961 represent an A1 domain-interactive site","volume":"44","author":"Ansong","year":"2005","journal-title":"Biochemistry"},{"key":"10.1016\/j.jtha.2025.12.006_bib30","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1111\/jth.13292","article-title":"Stabilizing interactions between D666-S1787 and T657-Y1792 at the A2-A3 interface support factor VIIIa stability in the blood clotting pathway","volume":"14","author":"Monaghan","year":"2016","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2025.12.006_bib31","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/j.1538-7836.2007.02458.x","article-title":"A3 domain residue Glu1829 contributes to A2 subunit retention in factor VIIIa","volume":"5","author":"Wakabayashi","year":"2007","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2025.12.006_bib32","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1042\/bj2630187","article-title":"Inhibition of human coagulation factor VIII by monoclonal antibodies. Mapping of functional epitopes with the use of recombinant factor VIII fragments","volume":"263","author":"Leyte","year":"1989","journal-title":"Biochem J"},{"key":"10.1016\/j.jtha.2025.12.006_bib33","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1182\/blood.V91.7.2347","article-title":"A human alloantibody interferes with binding of factor IXa to the factor VIII light chain","volume":"91","author":"Fijnvandraat","year":"1998","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2025.12.006_bib34","doi-asserted-by":"crossref","first-page":"15401","DOI":"10.1074\/jbc.274.22.15401","article-title":"The A1 and A2 subunits of factor VIIIa synergistically stimulate factor IXa catalytic activity","volume":"274","author":"Fay","year":"1999","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib35","doi-asserted-by":"crossref","first-page":"6027","DOI":"10.1074\/jbc.271.11.6027","article-title":"Model for the factor VIIIa-dependent decay of the intrinsic factor Xase. Role of subunit dissociation and factor IXa-catalyzed proteolysis","volume":"271","author":"Fay","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib36","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1016\/S0021-9258(19)50585-3","article-title":"Factor IXa enhances reconstitution of factor VIIIa from isolated A2 subunit and A1\/A3-C1-C2 dimer","volume":"267","author":"Lamphear","year":"1992","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib37","doi-asserted-by":"crossref","first-page":"9445","DOI":"10.1016\/S0021-9258(17)36901-6","article-title":"Factor IXa protects factor VIIIa from activated protein C. Factor IXa inhibits activated protein C-catalyzed cleavage of factor VIIIa at Arg562","volume":"269","author":"Regan","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2025.12.006_bib38","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.3390\/ijms23052762","article-title":"The molecular basis of FIX deficiency in hemophilia B","volume":"23","author":"Shen","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jtha.2025.12.006_bib39","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1111\/jth.15793","article-title":"Structural insights into blood coagulation factor VIII: Procoagulant complexes, membrane binding, and antibody inhibition","volume":"20","author":"Childers","year":"2022","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2025.12.006_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbagen.2023.130381","article-title":"Factor VIII A3 domain residues 1793-1795 represent a factor IXa-interactive site in the tenase complex","volume":"1867","author":"Takeyama","year":"2023","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"10.1016\/j.jtha.2025.12.006_bib41","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.str.2008.03.001","article-title":"Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex","volume":"16","author":"Ngo","year":"2008","journal-title":"Structure"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783625009018?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783625009018?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:17:37Z","timestamp":1781939857000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783625009018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["S1538783625009018"],"URL":"https:\/\/doi.org\/10.1016\/j.jtha.2025.12.006","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Defining the critical roles of factor VIII residues 1900 to 1908 in factor VIIIa\u2013factor IXa complex formation and factor VIIIa activity","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtha.2025.12.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}