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-induce d fulminant hepatitis, fetal loss syndrome, and xenograft rejection, the ma jor procoagulant has remained elusive. Here we describe the isolation and f unctional expression of a distinct human prothrombinase, termed FGL2. The m urine fgl2 gene product has been implicated in the pathophysiology of murin e fulminant hepatitis. The predicted ORF corresponds to a 439-amino-acid ty pe II integral membrane protein that contains a carboxy-terminal Fibrinogen -related domain. Functional analysis showed that FGL2-encoded protein is in deed a prothrombinase. This enzyme is a serine protease and directly cleave s prothrombin to thrombin. The FGL2 gene is a single-copy gene in the haplo id 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 put ative cis-elements including a TATA box, an AP1 site, CEBP sites, Spl site, and Ets binding domains. By both radiation hybrid analyses and fluorescenc e in situ hybridization, human FGL2 was localized to 7q11.23. (C) 2001 Acad emic Press.