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.