Schematic diagram outlining (A) the genomic organization of the human F9 gene. The exons (a-h) and introns are labeled according to the scheme proposed in . (B) FIX mRNA transcribed from F9. (C) The 461-aa precursor FIX protein, with its seven structural domains. (D) The 415-aa mature hFIX, found circulating in plasma, consists of five structural domains. (E) The 385-aa activated FIX (FIXa) contains an N-terminal light chain (composed of the Gla and EGF 1 and 2 domains), and is linked via a disulfide bond to the C-terminal heavy chain (containing the catalytic domain). See text for further details. The diagram is not drawn to scale.
The primary transcript of the F9 gene is ~2802 bases in length, and is made up of a short 5'-untranslated region (29 bases), an open reading frame (ORF) of 1383 bases, and a 3'-untranslated region (1390 bases). The ORF encodes a 461-amino acid (aa) precursor polypeptide, which is modified extensively before release into the bloodstream .
The F9 gene is phylogenetically conserved and shares high homology with the factor VII (F7), factor X (F10), and protein C genes. The basic exon structure of F9 is organized in a similar fashion to other coagulation factors such as factor VII (FVII) and FX, and protein C, suggesting that they all evolved from a common ancestral gene by duplication [1,4]. The eight exons of F9 encode a number of structural domains in the protein, which are identified according to structure and function and are discussed below.
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