Genomic characterization, localization, and functional expression of FGL2, the human gene encoding fibroleukin: a novel human procoagulant.
For diseases in which thrombosis plays a pivotal role, such as virus-induced fulminant hepatitis, fetal loss syndrome, and xenograft rejection, the major procoagulant has remained elusive. Here we describe the isolation and functional expression of a distinct human prothrombinase, termed FGL2. The murine fgl2 gene product has been implicated in the pathophysiology of murine fulminant hepatitis. The predicted ORF corresponds to a 439-amino-acid type II integral membrane protein that contains a carboxy-terminal Fibrinogen-related domain. Functional analysis showed that FGL2-encoded protein is indeed a prothrombinase. This enzyme is a serine protease and directly cleaves prothrombin to thrombin. The FGL2 gene is a single-copy gene in the haploid human genome and has two exons separated by a 2195-bp intron expressing two mRNA transcripts of 1.5 and 5.0 kb. The 5'-flanking region contains putative cis-elements including a TATA box, an AP1 site, CEBP sites, Sp1 site, and Ets binding domains. By both radiation hybrid analyses and fluorescence in situ hybridization, human FGL2 was localized to 7q11.23.
Yuwaraj
S
S
Multiorgan Transplant Program and Department of Medicine, Toronto General Hospital, University of Toronto, Ontario, M5G 2C4, Canada.
Ding
J
J
Liu
M
M
Marsden
P A
PA
Levy
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D016466:CHO Cells; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003029:Coagulants; D006224:Cricetinae; D005091:Exons; D005340:Fibrinogen / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017434:Protein Structure, Tertiary; D011516:Prothrombin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D021101:Radiation Hybrid Mapping; D017386:Sequence Homology, Amino Acid; D016324:Sequence Tagged Sites; D012697:Serine Endopeptidases / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection
D003029:Coagulants; C095202:FGL2 protein, human; C490637:Fgl2 protein, mouse; D012333:RNA, Messenger; D011516:Prothrombin; D005340:Fibrinogen; D013925:Thromboplastin; D012697:Serine Endopeptidases