Carboxy-terminal-extended variant of the human fibrinogen .alpha. subunit: a novel exon conferring marked homology to .beta. and .gamma. subunits

• Published in: Biochemistry (Easton) Vol. 31; no. 48; pp. 11968 - 11972
• Main Authors: Fu, Yiping, Weissbach, Lawrence, Plant, Patricia W, Oddoux, Carole, Cao, Yan, Liang, T. Jake, Roy, Samar N, Redman, Colvin M, Grieninger, Gerd
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 08-12-1992
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Base Sequence; Biological and medical sciences; Cells, Cultured; DNA; Electrophoresis, Polyacrylamide Gel; Exons; Fibrinogen - genetics; Fundamental and applied biological sciences. Psychology; Humans; Miscellaneous; Molecular Sequence Data; Open Reading Frames; Proteins; RNA Splicing; Sequence Homology, Amino Acid; Tumor Cells, Cultured; Human; C terminal-Sequence; Alternative splicing; Messenger RNA; Liver; Sequence alignment; Fibrinogen; Homology; Subunit; Aminoacid sequence
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00163a002

Similarities between the N-terminal regions of the three subunits of the clotting protein fibrinogen--(alpha beta gamma)2--suggest that they evolved from a common progenitor. However, to date no human alpha chain has been found with the strong C-terminal homology shared by the beta and gamma chains. Here we examine the natural product of a novel fibrinogen alpha chain transcript bearing a separate open reading frame that supplies the missing C-terminal homology to the other chains. Additional splicing leads to the use of this extra sequence as a sixth exon elongating the alpha chain by 35%. Since the extended alpha chain (alpha E) is assembled into fibrinogen molecules and its synthesis is enhanced by interleukin-6, it suggests participation in both the acute phase response and normal physiology.