{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:24:21Z","timestamp":1787156661693,"version":"build-2736575974"},"reference-count":40,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Shanghai Municipal Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007219","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":[[2026,9]]},"DOI":"10.1016\/j.jtha.2026.06.006","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:37:41Z","timestamp":1781246261000},"page":"3213-3223","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trp83 is vital to the interaction with phospholipids in \u03b3-carboxyglutamic acid domain of protein C"],"prefix":"10.1016","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7097-3981","authenticated-orcid":false,"given":"Junwei","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanqun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiulan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenman","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9934-1128","authenticated-orcid":false,"given":"Yeling","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtha.2026.06.006_bib1","doi-asserted-by":"crossref","first-page":"10212","DOI":"10.1073\/pnas.93.19.10212","article-title":"The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex","volume":"93","author":"Stearns-Kurosawa","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jtha.2026.06.006_bib2","doi-asserted-by":"crossref","first-page":"26104","DOI":"10.1016\/S0021-9258(18)35723-5","article-title":"The function of calcium in protein C activation by thrombin and the thrombin-thrombomodulin complex can be distinguished by mutational analysis of protein C derivatives","volume":"267","author":"Rezaie","year":"1992","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib3","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0005-2744(79)90103-7","article-title":"The inhibition of blood coagulation by activated protein C through the selective inactivation of activated Factor V","volume":"571","author":"Walker","year":"1979","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.jtha.2026.06.006_bib4","doi-asserted-by":"crossref","first-page":"31869","DOI":"10.1016\/S0021-9258(18)31776-9","article-title":"The mechanism of inactivation of human factor V and human factor Va by activated protein C","volume":"269","author":"Kalafatis","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib5","doi-asserted-by":"crossref","first-page":"4708","DOI":"10.1182\/blood.V87.11.4708.bloodjournal87114708","article-title":"Comparison of activated protein C\/protein S-mediated inactivation of human factor VIII and factor V","volume":"87","author":"Lu","year":"1996","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.06.006_bib6","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1126\/science.1071699","article-title":"Activation of endothelial cell protease activated receptor 1 by the protein C pathway","volume":"296","author":"Riewald","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.jtha.2026.06.006_bib7","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1182\/blood-2012-08-452169","article-title":"Biased agonism of protease-activated receptor 1 by activated protein C caused by noncanonical cleavage at Arg46","volume":"120","author":"Mosnier","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.06.006_bib8","doi-asserted-by":"crossref","first-page":"24851","DOI":"10.1074\/jbc.C200163200","article-title":"The crystal structure of the endothelial protein C receptor and a bound phospholipid","volume":"277","author":"Oganesyan","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib9","doi-asserted-by":"crossref","first-page":"28850","DOI":"10.1074\/jbc.M604966200","article-title":"Multifunctional specificity of the protein C\/activated protein C Gla domain","volume":"281","author":"Preston","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib10","doi-asserted-by":"crossref","first-page":"12040","DOI":"10.1016\/S0021-9258(19)50305-2","article-title":"The contributions of individual gamma-carboxyglutamic acid residues in the calcium-dependent binding of recombinant human protein C to acidic phospholipid vesicles","volume":"268","author":"Zhang","year":"1993","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib11","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1016\/j.jtha.2025.07.030","article-title":"Novel insights into inherited protein C deficiency from an interactive PROC variant database","volume":"23","author":"Zhang","year":"2025","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.06.006_bib12","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1111\/jth.15732","article-title":"Diagnosis and management of severe congenital protein C deficiency (SCPCD): communication from the SSC of the ISTH","volume":"20","author":"Minford","year":"2022","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.06.006_bib13","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/S0140-6736(83)91216-3","article-title":"Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant","volume":"2","author":"Branson","year":"1983","journal-title":"Lancet"},{"key":"10.1016\/j.jtha.2026.06.006_bib14","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.braindev.2015.07.004","article-title":"Fetal hydrocephalus and neonatal stroke as the first presentation of protein C deficiency","volume":"38","author":"Ichiyama","year":"2016","journal-title":"Brain Dev"},{"key":"10.1016\/j.jtha.2026.06.006_bib15","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/j.1365-2516.2008.01838.x","article-title":"Protein C deficiency","volume":"14","author":"Goldenberg","year":"2008","journal-title":"Haemophilia"},{"key":"10.1016\/j.jtha.2026.06.006_bib16","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.5858\/2002-126-1337-LIIDAO","article-title":"Laboratory issues in diagnosing abnormalities of protein C, thrombomodulin, and endothelial cell protein C receptor","volume":"126","author":"Kottke-Marchant","year":"2002","journal-title":"Arch Pathol Lab Med"},{"key":"10.1016\/j.jtha.2026.06.006_bib17","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.thromres.2015.03.010","article-title":"Natural anticoagulants deficiency and the risk of venous thromboembolism: a meta-analysis of observational studies","volume":"135","author":"Di Minno","year":"2015","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2026.06.006_bib18","article-title":"Genetic background analysis of protein C deficiency demonstrates a recurrent mutation associated with venous thrombosis in Chinese population","volume":"7","author":"Tang","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2026.06.006_bib19","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3324\/haematol.2010.037515","article-title":"Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group","volume":"96","author":"Zhu","year":"2011","journal-title":"Haematologica"},{"key":"10.1016\/j.jtha.2026.06.006_bib20","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1182\/blood-2014-12-617274","article-title":"Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays","volume":"125","author":"Ding","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.06.006_bib21","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1055\/a-2569-6439","article-title":"Asn384Ser mutation in protein C is associated with multiple-site thrombosis in a young heterozygous male","volume":"126","author":"Yuan","year":"2026","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.06.006_bib22","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1160\/TH17-01-0043","article-title":"Gly74Ser mutation in protein C causes thrombosis due to a defect in protein S-dependent anticoagulant function","volume":"117","author":"Chen","year":"2017","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.06.006_bib23","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/jth.14777","article-title":"Gly197Arg mutation in protein C causes recurrent thrombosis in a heterozygous carrier","volume":"18","author":"Lu","year":"2020","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.06.006_bib24","article-title":"Anticoagulant protein C p.Lys193del mutation and promoter region polymorphisms: Genetic risk factors of deep venous thrombosis","volume":"2","author":"Xu-qian","year":"2025","journal-title":"LabMed Discov"},{"key":"10.1016\/j.jtha.2026.06.006_bib25","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.lmd.2025.100107","article-title":"Laboratory diagnosis of juvenile thrombophilia from compound heterozygous protein C variants: a family report and literature review","volume":"2","author":"Meng","year":"2025","journal-title":"LabMed Discov"},{"key":"10.1016\/j.jtha.2026.06.006_bib26","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1055\/s-0038-1648908","article-title":"Homozygous type I protein C deficiency in two unrelated families exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His mutations","volume":"72","author":"Long","year":"1994","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.06.006_bib27","doi-asserted-by":"crossref","first-page":"26279","DOI":"10.1074\/jbc.272.42.26279","article-title":"The interaction between the endothelial cell protein C receptor and protein C is dictated by the gamma-carboxyglutamic acid domain of protein C","volume":"272","author":"Regan","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib28","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1182\/blood.V97.6.1685","article-title":"Endothelial cell protein C receptor plays an important role in protein C activation in vivo","volume":"97","author":"Taylor","year":"2001","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.06.006_bib29","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1073\/pnas.0611493104","article-title":"Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cells","volume":"104","author":"Bae","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jtha.2026.06.006_bib30","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2106623118","article-title":"aPC\/PAR1 confers endothelial anti-apoptotic activity via a discrete, \u03b2-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis","volume":"118","author":"Molinar-Inglis","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jtha.2026.06.006_bib31","doi-asserted-by":"crossref","first-page":"31751","DOI":"10.1074\/jbc.274.45.31751","article-title":"The structure and assembly of secreted mucins","volume":"274","author":"Perez-Vilar","year":"1999","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1742-4658.2009.07429.x","article-title":"Mucin-type O-glycosylation--putting the pieces together","volume":"277","author":"Jensen","year":"2010","journal-title":"FEBS J"},{"key":"10.1016\/j.jtha.2026.06.006_bib33","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1016\/S0021-9258(18)94333-4","article-title":"The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis","volume":"244","author":"Weber","year":"1969","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib34","doi-asserted-by":"crossref","first-page":"26s","DOI":"10.1378\/chest.124.3_suppl.26S","article-title":"The protein C pathway","volume":"124","author":"Esmon","year":"2003","journal-title":"Chest"},{"key":"10.1016\/j.jtha.2026.06.006_bib35","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0006-3495(99)76875-X","article-title":"Probing the structural changes in the light chain of human coagulation factor VIIa due to tissue factor association","volume":"77","author":"Perera","year":"1999","journal-title":"Biophys J"},{"key":"10.1016\/j.jtha.2026.06.006_bib36","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.1016\/S0021-9258(17)41904-1","article-title":"The binding energy of human coagulation protein C to acidic phospholipid vesicles contains a major contribution from leucine 5 in the gamma-carboxyglutamic acid domain","volume":"269","author":"Zhang","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.06.006_bib37","doi-asserted-by":"crossref","first-page":"10376","DOI":"10.1021\/bi00033a008","article-title":"Hydrophobic amino acid residues of human anticoagulation protein C that contribute to its functional binding to phospholipid Vesicles","volume":"34","author":"Christiansen","year":"1995","journal-title":"Biochemistry"},{"key":"10.1016\/j.jtha.2026.06.006_bib38","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1016\/S0006-3495(00)76530-1","article-title":"Modeling zymogen protein C","volume":"79","author":"Perera","year":"2000","journal-title":"Biophys J"},{"key":"10.1016\/j.jtha.2026.06.006_bib39","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.1021\/bi00025a014","article-title":"Structure-function assessment of the role of the helical stack domain in the properties of human recombinant protein C and activated protein C","volume":"34","author":"Christiansen","year":"1995","journal-title":"Biochemistry"},{"key":"10.1016\/j.jtha.2026.06.006_bib40","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1432-1033.2004.04401.x","article-title":"Selective modulation of protein C affinity for EPCR and phospholipids by Gla domain mutation","volume":"272","author":"Preston","year":"2005","journal-title":"FEBS J"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626003855?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626003855?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:27:39Z","timestamp":1787153259000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783626003855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S1538783626003855"],"URL":"https:\/\/doi.org\/10.1016\/j.jtha.2026.06.006","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Trp83 is vital to the interaction with phospholipids in \u03b3-carboxyglutamic acid domain of protein C","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtha.2026.06.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 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"}]}}