{'fraction_non_alphanumeric': 0.03088538091969801, 'fraction_numerical': 0.024021962937542895, 'mean_word_length': 5.0, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Roles of Phytanoyl-CoA α-Hydroxylase in Mediating the Expression of Human Coagulation Factor VIII*

The coagulation factor VIII (FVIII) is the coagulation factor deficient in the X-chromosome-linked bleeding disorder hemophilia A. Previous transfection studies demonstrated that factor VIII was 10–100-fold less efficiently expressed than the homologous coagulation factor, factor V. To investigate the regulatory mechanisms of FVIII synthesis and secretion, we used the yeast two-hybrid system as an approach to search for proteins that associated with FVIII. The A2 domain (337–740 amino acids) of factor VIII (FVIII-A2) was used as a bait and phytanoyl-CoA α-hydroxylase (PAHX) was identified as a binding protein of FVIII-A2. PAHX had potential to interact with the residues 373–508 within the A2 domain, but not with A1 and A3 (the homologous domains of A2). The interaction between the A2 domain and PAHX was independent of the type 2 peroxisomal targeting signal (PTS2) of PAHX. Overexpression of PAHX in FVIII-produced cells decreased the expression of FVIII by about 70%. The elevated expression of von Willebrand factor had no effect on the suppression of FVIII secretion by PAHX. Expression of the green fluorescent PAHX fusion protein in SMMC-7721 cells affected the intracellular trafficking of FVIII-A2. These results suggested that the interaction between PAHX and FVIII-A2 was in part responsible for the low-level expression of factor VIII.