Disease relevance of TSTA3

• Specifically, FX showed a remarkable similarity with a putative Escherichia coli protein, named Yefb, whose gene maps in a region of E. coli chromosome coding for enzymes involved in synthesis and utilization of GDP-D-mannose [1].
• Tumor-microenvironment interactions: the fucose-generating FX enzyme controls adhesive properties of colorectal cancer cells [2].
• If this hypothesis will be confirmed the FX enzyme could become a target molecule for metastasis prevention [2].
• The levels of FX gene expression in some human hepatoma and hepatocyte cell lines were determined [3].
• In a previous study, we demonstrated that the fucose-generating FX enzyme regulates the expression of selectin ligands by B and T lymphocytes and by head and neck squamous cell carcinoma cells [2].

High impact information on TSTA3

• Factor X (FX) is a vitamin K-dependent plasma protein required for the intrinsic and extrinsic pathways of blood coagulation [4].
• To test this hypothesis, we compared the expression of wild type and mutant FX cDNA in a human kidney cell line [4].
• FXSanto Domingo is a hereditary FX deficiency which is characterized clinically by a severe bleeding diathesis [4].
• We generated an amphotropic retroviral vector with the human FX cDNA and delivered it to rat hepatocytes in vivo during liver regeneration [5].
• Human erythrocytes contain a nicotinamide adenine dinucleotide phosphate (NADP[H])-binding protein, FX, whose levels are significantly increased in erythrocytes from glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals bearing the mediterranean variant of G6PD [6].

Chemical compound and disease context of TSTA3

• Relationship between elevated FX expression and increased production of GDP-L-fucose, a common donor substrate for fucosylation in human hepatocellular carcinoma and hepatoma cell lines [3].
• We also found that highly metastatic colorectal cancer variants express higher levels of FX and of sialyl Lewis-a than low metastatic variants originating in the same tumors [2].

Biological context of TSTA3

• The reported P35B cDNA contains an open reading frame (ORF) of 813 bp and encodes a putative protein of 271 amino acids (30 kD), whereas FX protein is 320 amino acids in length (35.81 kD, in good agreement with previous studies) [6].
• Recently, on the basis of partial amino acid sequence, it proved to be the human homolog of the murine protein P35B, a tumor rejection antigen [1].
• This latter finding obviously favors the conclusion that "autosomal" rather than "X-linked" genes are involved in the determination of the FX levels [7].
• In this family, two differently affected FX genes are present, leading to double heterozygosity of the proposita and thus excluding consanguinity of parents [8].
• Preliminary data indicated that the levels of this protein are significantly increased in hemizygotes, heterozygotes, and homozygotes for the G6PD Mediterranean mutant, thus raising the question of whether or not the individual variation in FX levels is more or less directly influenced by X-linked genes [7].

Anatomical context of TSTA3

• It was also shown that the FX enzyme regulated important interaction parameters between these cancer cells and endothelial cells [2].
• To address these limitations, we developed a flow cytometric assay to directly measure the binding of FX to monocytes in whole blood [9].
• The FX enzyme is a functional component of lymphocyte activation [10].
• From a panel of 17 reactive hybridomas to FX, 3 were selected for further characterisation [11].
• Four Irish children with severe FX deficiency presented with umbilical cord bleeding [12].

Associations of TSTA3 with chemical compounds

• Synthesis of GDP-L-fucose by the human FX protein [1].
• This enzyme generates GDP-mannose-4-keto-6-D-deoxymannose from GDP-mannose, which is then converted by the FX protein (GDP-4-keto-6-D-deoxymannose epimerase/GDP-4-keto-6-L-galactose reductase) to GDP-L-fucose [13].
• Using purified recombinant human GDP-mannose 4,6-dehydratase and FX protein (GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase), we show that the two proteins alone are sufficient to convert GDP-mannose to GDP-fucose in vitro [14].
• Specifically, purified FX apparently catalyzes a combined epimerase and NADPH-dependent reductase reaction, converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose [1].
• Genetic variation in the quantitative levels of an NADP (H)-binding protein (FX) in human erythrocytes [7].

Other interactions of TSTA3

• These results suggest that metabolites generated in this pathway may participate in the transcriptional regulation of the FX protein and possibly the GMD protein [13].
• The recombinant GFS was a homodimer with an optimum pH of 8 [15].
• Upon activation, monocytes express the alphaMbeta2 integrin CD11b/CD18, which has a binding site for the plasma protein FX [9].

Analytical, diagnostic and therapeutic context of TSTA3

• Mapping of the genes encoding tum- transplantation antigens P91A, P35B, and P198 [16].
• Neonatal intramuscular injection resulted in expression of hFX at 248 ng/ml (3.1% of normal), which derived from both liver and muscle [17].
• We conclude that neonatal gene therapy with an AAV vector with the CMV-beta-actin promoter might correct hemophilia due to hFX deficiency [17].
• A radioimmunoassay (RIA) demonstrated a 5,100-fold increase in the levels of FX activation peptide after exposure to sarcoma extract [18].
• The mutation causing the Glu102Lys substitution was introduced by site directed mutagenesis into a wild-type FX cDNA, and recombinant protein was expressed in HEK 293 cells [19].

References