{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:15:07Z","timestamp":1789953307792,"version":"4.0.1"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T00:00:00Z","timestamp":1443484800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA51008"],"award-info":[{"award-number":["P30 CA51008"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RO1 CA135069"],"award-info":[{"award-number":["RO1 CA135069"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA168926"],"award-info":[{"award-number":["U01 CA168926"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministry of Education, Youth and Sports","doi-asserted-by":"publisher","award":["LH13051"],"award-info":[{"award-number":["LH13051"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["P206\/12\/0503"],"award-info":[{"award-number":["P206\/12\/0503"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Glycan Connections, LLC","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic liver diseases are a serious health problem worldwide. One of the frequently reported glycan alterations in liver disease is aberrant fucosylation, which was suggested as a marker for noninvasive serologic monitoring. We present a case study that compares site specific glycoforms of four proteins including haptoglobin, complement factor H, kininogen-1, and hemopexin isolated from the same patient. Our exoglycosidase-assisted LC\u2013MS\/MS analysis confirms the high degree of fucosylation of some of the proteins but shows that microheterogeneity is protein- and site-specific. MSn analysis of permethylated detached glycans confirms the presence of LeY glycoforms on haptoglobin, which cannot be detected in hemopexin or complement factor H; all three proteins carry Lewis and H epitopes. Core fucosylation is detectable in only trace amounts in haptoglobin but with confidence on hemopexin and complement factor H, where core fucosylation of the bi-antennary glycans on select glycopeptides reaches 15\u201320% intensity. These protein-specific differences in fucosylation, observed in proteins isolated from the same patient source, suggest that factors other than up-regulation of enzymatic activity regulate the microheterogeneity of glycoforms. This has implications for selection of candidate proteins for disease monitoring and suggests that site-specific glycoforms have structural determinants, which could lead to functional consequences for specific subsets of proteins or their domains.<\/jats:p>","DOI":"10.1021\/pr5005482","type":"journal-article","created":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T17:24:55Z","timestamp":1412011495000},"page":"5561-5569","source":"Crossref","is-referenced-by-count":32,"title":["Protein and Site Specificity\nof Fucosylation in Liver-Secreted\nGlycoproteins"],"prefix":"10.1021","volume":"13","author":[{"given":"Petr","family":"Pompach","sequence":"first","affiliation":[{"name":"Czech Academy of Sciences , , Videnska 1083 ,","place":[", Prague, Czech Republic, 142 20"]},{"name":"Charles University , , Hlavova 8 , ,","place":["Prague, Czech Republic, 128 43"]},{"name":"Georgetown University , , 3970 Reservoir Road NW , , ,","place":["Washington, DC, United States, 20007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Ashline","sequence":"additional","affiliation":[{"name":"University of New Hampshire , , , ,","place":["Durham, New Hampshire, United States, 03824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Brnakova","sequence":"additional","affiliation":[{"name":"Georgetown University , , 3970 Reservoir Road NW , , ,","place":["Washington, DC, United States, 20007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Benicky","sequence":"additional","affiliation":[{"name":"Georgetown University , , 3970 Reservoir Road NW , , ,","place":["Washington, DC, United States, 20007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miloslav","family":"Sanda","sequence":"additional","affiliation":[{"name":"Georgetown University , , 3970 Reservoir Road NW , , ,","place":["Washington, DC, United States, 20007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radoslav","family":"Goldman","sequence":"additional","affiliation":[{"name":"Georgetown University , , 3970 Reservoir Road NW , , ,","place":["Washington, DC, United States, 20007"]},{"name":"Georgetown University , , , ,","place":["Washington, DC, United States, 20007"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,9,29]]},"reference":[{"key":"2026090111100863000_cit1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1146\/annurev.bi.54.070185.003215","article-title":"Assembly of asparagine-linked\noligosaccharides","volume":"54","author":"Kornfeld","year":"1985","journal-title":"Annu. Rev. Biochem."},{"issue":"1","key":"2026090111100863000_cit2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0092-8674(85)90034-0","article-title":"Demonstration of an extensive trans-tubular\nnetwork\ncontinuous with the Golgi apparatus stack that may function in glycosylation","volume":"43","author":"Roth","year":"1985","journal-title":"Cell"},{"key":"2026090111100863000_cit3","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1146\/annurev.biochem.76.061005.092322","article-title":"Glycosyltransferases:\nstructures, functions, and mechanisms","volume":"77","author":"Lairson","year":"2008","journal-title":"Annu.\nRev. Biochem."},{"issue":"38","key":"2026090111100863000_cit4","doi-asserted-by":"crossref","first-page":"29511","DOI":"10.1074\/jbc.M110.145938","article-title":"Analysis\nof site-specific glycosylation of renal and hepatic \u03b3-glutamyl\ntranspeptidase from normal human tissue","volume":"285","author":"West","year":"2010","journal-title":"J.\nBiol. Chem."},{"issue":"12","key":"2026090111100863000_cit5","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1002\/cncr.26490","article-title":"Fucosylated haptoglobin is a novel type of cancer biomarker\nlinked to the prognosis after an operation in colorectal cancer","volume":"118","author":"Takeda","year":"2012","journal-title":"Cancer"},{"issue":"6","key":"2026090111100863000_cit6","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1158\/1055-9965.EPI-11-1183","article-title":"Increased levels of tetra-antennary N-linked glycan but not core\nfucosylation are associated with hepatocellular carcinoma tissue","volume":"21","author":"Mehta","year":"2012","journal-title":"Cancer Epidemiol., Biomarkers Prev."},{"issue":"16","key":"2026090111100863000_cit7","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1002\/pmic.200800046","article-title":"Fucosylated haptoglobin\nis a novel marker for pancreatic\ncancer: detailed analyses of oligosaccharide structures","volume":"8","author":"Miyoshi","year":"2008","journal-title":"Proteomics"},{"issue":"6","key":"2026090111100863000_cit8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/bmc.167","article-title":"A preliminary evaluation\nof the differences in the glycosylation of alpha-1-acid glycoprotein\nbetween individual liver diseases","volume":"16","author":"Anderson","year":"2002","journal-title":"Biomed. Chromatogr."},{"key":"2026090111100863000_cit9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/1476-4598-9-215","article-title":"Serum N-glycome\nbiomarker for monitoring development of DENA-induced hepatocellular\ncarcinoma in rat","volume":"9","author":"Fang","year":"2010","journal-title":"Mol. Cancer"},{"issue":"5","key":"2026090111100863000_cit10","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1074\/mcp.M112.023259","article-title":"Site specific glycoforms of haptoglobin in liver cirrhosis\nand hepatocellular carcinoma","volume":"12","author":"Pompach","year":"2013","journal-title":"Mol. Cell. Proteomics"},{"issue":"6","key":"2026090111100863000_cit11","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1021\/pr301217b","article-title":"Glycoproteomic\ndiscovery of serological\nbiomarker candidates for HCV\/HBV infection-associated liver fibrosis\nand hepatocellular carcinoma","volume":"12","author":"Kaji","year":"2013","journal-title":"J. Proteome. Res."},{"issue":"5","key":"2026090111100863000_cit12","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1074\/mcp.M112.023325","article-title":"Quantitative LC-MS-MRM analysis of\nsite-specific glycoforms\nof haptoglobin in liver disease","volume":"12","author":"Sanda","year":"2013","journal-title":"Mol. Cell.\nProteomics."},{"issue":"8","key":"2026090111100863000_cit13","doi-asserted-by":"crossref","first-page":"e12419","DOI":"10.1371\/journal.pone.0012419","article-title":"Linkage specific fucosylation\nof alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications\nfor a biomarker of hepatocellular carcinoma","volume":"5","author":"Comunale","year":"2010","journal-title":"PLoS One"},{"issue":"5","key":"2026090111100863000_cit14","first-page":"823","article-title":"Diagnostic value of the hemopexin N-glycan profile\nin hepatocellular carcinoma patients","volume":"56","author":"Debruyne","year":"2010","journal-title":"Physiol.\nRev."},{"issue":"6","key":"2026090111100863000_cit15","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/j.1440-1746.1998.tb00699.x","article-title":"Serum N-acetylglucosaminyltransferase\nIII activities in hepatocellular carcinoma","volume":"13","author":"Mori","year":"1998","journal-title":"J. Gastroenterol. Hepatol."},{"issue":"2","key":"2026090111100863000_cit16","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1530-0277.1994.tb00031.x","article-title":"Microheterogeneity of serum glycoproteins\nin alcoholics: is desialo-transferrin the marker of chronic alcohol\ndrinking or alcoholic liver injury?","volume":"18","author":"Tsutsumi","year":"1994","journal-title":"Alcohol.:\nClin. Exp. Res."},{"issue":"2","key":"2026090111100863000_cit17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1432-1033.1989.tb15032.x","article-title":"Presence of fucosylated triantennary, tetraantennary and pentaantennary\nglycans in transferrin synthesized by the human hepatocarcinoma cell\nline Hep G2","volume":"184","author":"Campion","year":"1989","journal-title":"Eur. J. Biochem."},{"issue":"2","key":"2026090111100863000_cit18","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1021\/pr800752c","article-title":"Identification and Development of\nFucosylated Glycoproteins as Biomarkers of Primary Hepatocellular\nCarcinoma","volume":"8","author":"Comunale","year":"2009","journal-title":"J. Proteome Res."},{"issue":"12","key":"2026090111100863000_cit19","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1093\/glycob\/cwm100","article-title":"Ovarian cancer is associated with\nchanges in glycosylation\nin both acute-phase proteins and IgG","volume":"17","author":"Saldova","year":"2007","journal-title":"Glycobiology"},{"issue":"3","key":"2026090111100863000_cit20","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1021\/pr101036b","article-title":"Glycomic and glycoproteomic\nanalysis of serum from patients with stomach cancer reveals potential\nmarkers arising from host defense response mechanisms","volume":"10","author":"Bones","year":"2011","journal-title":"J. Proteome. Res."},{"issue":"3","key":"2026090111100863000_cit21","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s13361-013-0776-9","article-title":"Structural\ndocumentation\nof glycan epitopes: sequential mass spectrometry and spectral matching","volume":"25","author":"Ashline","year":"2014","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"12","key":"2026090111100863000_cit22","doi-asserted-by":"crossref","first-page":"5095","DOI":"10.1021\/ac100131e","article-title":"Chip-based\nreversed-phase liquid chromatography-mass spectrometry of permethylated\nN-linked glycans: a potential methodology for cancer-biomarker discovery","volume":"82","author":"Alley","year":"2010","journal-title":"Anal. Chem."},{"issue":"23","key":"2026090111100863000_cit23","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1002\/rcm.2210","article-title":"Solid-phase permethylation\nof glycans for mass spectrometric analysis","volume":"19","author":"Kang","year":"2005","journal-title":"Rapid Commun. Mass Spectrom."},{"issue":"3","key":"2026090111100863000_cit24","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1021\/pr201183w","article-title":"Semi-automated\nidentification of N-Glycopeptides by hydrophilic interaction chromatography,\nnano-reverse-phase LC-MS\/MS, and glycan database search","volume":"11","author":"Pompach","year":"2012","journal-title":"J. Proteome. Res."},{"issue":"8","key":"2026090111100863000_cit25","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1021\/pr400196s","article-title":"Exploring\nSite-Specific\nN-Glycosylation Microheterogeneity of Haptoglobin Using Glycopeptide\nCID Tandem Mass Spectra and Glycan Database Search","volume":"12","author":"Chandler","year":"2013","journal-title":"J. Proteome. Res."},{"issue":"1","key":"2026090111100863000_cit26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ab.2007.12.012","article-title":"HPLC-based\nanalysis of serum N-glycans on a 96-well plate platform with dedicated\ndatabase software","volume":"376","author":"Royle","year":"2008","journal-title":"Anal. Biochem."},{"issue":"1","key":"2026090111100863000_cit27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0014-5793(87)80748-2","article-title":"Histidine-rich glycoprotein\nis evolutionarily related to the cystatin\nsuperfamily. Presence of two cystatin domains in the N-terminal region","volume":"216","author":"Koide","year":"1987","journal-title":"FEBS Lett."},{"issue":"1\u20132","key":"2026090111100863000_cit28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0009-8981(01)00586-1","article-title":"Hemopexin: a review of biological aspects and the role\nin laboratory medicine","volume":"312","author":"Delanghe","year":"2001","journal-title":"Clin. Chim. Acta"},{"issue":"11","key":"2026090111100863000_cit29","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1002\/rcm.2509","article-title":"Mass spectrometry\nof proton adducts of fucosylated N-glycans: fucose transfer between\nantennae gives rise to misleading fragments","volume":"20","author":"Wuhrer","year":"2006","journal-title":"Rapid Commun. Mass Spectrom."},{"issue":"2","key":"2026090111100863000_cit30","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1432-1033.1986.tb09421.x","article-title":"Completion\nof the primary structure of human high-molecular-mass kininogen. The\namino acid sequence of the entire heavy chain and evidence for its\nevolution by gene triplication","volume":"154","author":"Kellermann","year":"1986","journal-title":"Eur. J. Biochem."},{"issue":"2","key":"2026090111100863000_cit31","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1432-1033.1985.tb09199.x","article-title":"The amino\nacid sequence of the light chain of human high-molecular-mass kininogen","volume":"152","author":"Lottspeich","year":"1985","journal-title":"Eur. J. Biochem."},{"key":"2026090111100863000_cit32","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1749-6632.2011.06420.x","article-title":"Acute phase glycoproteins: bystanders or participants\nin carcinogenesis?","volume":"1253","author":"Dempsey","year":"2012","journal-title":"Ann. N.Y. Acad. Sci."},{"issue":"5","key":"2026090111100863000_cit33","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1084\/jem.144.5.1147","article-title":"Modulation of the alternative\ncomplement pathways by beta 1 H globulin","volume":"144","author":"Whaley","year":"1976","journal-title":"J.\nExp. Med."},{"issue":"2","key":"2026090111100863000_cit34","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1042\/bj2490593","article-title":"The complete amino\nacid sequence of human complement factor H","volume":"249","author":"Ripoche","year":"1988","journal-title":"Biochem. J."},{"issue":"11","key":"2026090111100863000_cit35","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1016\/j.bbamcr.2013.04.001","article-title":"N-linked protein\nglycosylation in the ER","volume":"1833","author":"Aebi","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"2026090111100863000_cit36","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.biochem.69.1.69","article-title":"Protein\nglucosylation and its role in protein folding","volume":"69","author":"Parodi","year":"2000","journal-title":"Annu. Rev. Biochem."},{"issue":"11","key":"2026090111100863000_cit37","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1093\/glycob\/cws110","article-title":"Site-specific glycoproteomics confirms that protein\nstructure dictates formation of N-glycan type, core fucosylation and\nbranching","volume":"22","author":"Thaysen-Andersen","year":"2012","journal-title":"Glycobiology"}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/pr5005482","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/12\/5561\/13538055\/pr5005482.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/12\/5561\/13538055\/pr5005482.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:15:33Z","timestamp":1788275733000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/13\/12\/5561\/1339556\/Protein-and-Site-Specificity-of-Fucosylation-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,29]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,9,29]]},"published-print":{"date-parts":[[2014,12,5]]}},"URL":"https:\/\/doi.org\/10.1021\/pr5005482","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,29]]}}}