Structure of the gene for human coagulation factor V

Abstract

Activated factor V (Va) serves as an essential protein cofactor for the conversion of prothrombin to thrombin by factor Xa. Analysis of the factor V cDNA indicates that the protein contains several types of internal repeats with the following domain structure: A1-A2-B-A3-C1-C2. In this report we describe the isolation and characterization of genomic DNA coding for human factor V. The factor V gene contains 25 exons which range in size from 72 to 2820 bp. The structure of the gene for factor V is similar to the previously characterized gene for factor VIII. Based on the aligned amino acid sequences of the two proteins, 21 of the 24 intron-exon boundaries in the factor V gene occur at the same location as in the factor VIII gene. In both genes, the junctions of the A1-A2 and A2-A3 domains are each encoded by a single exon. In contrast, the boundaries between domains A3-C1 and C1-C2 occur at intron-exon boundaries, which is consistent with evolution through domain duplication and exon shuffling. The connecting region or B domain of factor V is encoded by a single large exon of 2820 bp. The corresponding exon of the factor VIII gene contains 3106 bp. The 5' and 3' ends of both of these exons encode sequences homologous to the carboxyl-terminal end of domain A2 and the amino-terminal end of domain A3 in ceruloplasmin. There is otherwise no homology between the B domain exons.(ABSTRACT TRUNCATED AT 250 WORDS)

A Bipartite Autoinhibitory Region within the B-domain Suppresses Function in Factor V

“…The BR and AR are separated in the primary sequence of human FV by ϳ480 amino acids. Interestingly, approximately half of this region has 31 copies of 9-amino acid tandem repeats (9,45,46). However, lower vertebrates such as lizard, chicken, and pufferfish do not have any repeat segments, and the length separating the BR and AR is very short at Ͻ55 residues in these species.…”

Low prevalence of Factor V Leiden and the prothrombin G20210A mutation in a healthy population from the central-south region of Chile

“…13 The magnification and the digestion of DNA were carried out according to what was previously described. 14 Briefly, the PCR RFLP (Polymerase Chain Reaction, Restriction Fragment Length Polymorphism) was carried out with the primer 1: 5'-TGCC CAGT GCTTA ACAA GACCA-3' and primer 2: 5'-TGTTATCACACTGGTGCTAA-3'.…”

Molecular Pathophysiology of Thrombotic States and Their Impact to Laboratory Diagnostics

“…In the inactive form FV acts as APC co-factor in the regulatory activity of FV, IIIa. In inherited and acquired defects, this double role allows FV to influence the manifestation of these disorders into hemorrhagic or thrombotic forms 47,48 . To determine this manifestation, it is necessary to recognize precisely the procoagulation and anticoagulation forms of FV.…”