FUT3 Human
Description
Introduction to FUT3 Human
Fucosyltransferase 3 (FUT3), encoded by the FUT3 gene on chromosome 19p13.3, is a critical enzyme in glycosylation processes. It catalyzes the transfer of L-fucose to glycoconjugates via α(1,3) and α(1,4) linkages, synthesizing Lewis blood group antigens (Leᵃ, Leᵇ, Leˣ, Leʸ) and sialyl Lewis antigens (sLeᵃ, sLeˣ) . These antigens play roles in cell adhesion, inflammation, cancer metastasis, and microbial interactions .
Gene and Protein Features
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Enzyme Class: Golgi-resident type II transmembrane protein with dual α(1,3)/α(1,4)-fucosyltransferase activity .
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Catalytic Specificity: Prefers type 1 (Galβ1-3GlcNAc) over type 2 (Galβ1-4GlcNAc) chains, forming Leᵃ/Leᵇ and Leˣ/Leʸ antigens, respectively .
Key Functional Domains
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Substrate binding regions critical for fucose transfer to N-acetylglucosamine (GlcNAc) or glucose (Glc) .
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Mutations in catalytic domains (e.g., T202C, T1067A) reduce or abolish enzymatic activity .
Cancer
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Pancreatic Cancer: FUT3 overexpression correlates with enhanced cell proliferation, migration, and epithelial-mesenchymal transition (EMT). Knockdown reduces tumor growth in vivo (mean tumor volume: 14.83 ± 12.62 mm³ vs. 678.83 ± 88.2 mm³ in controls) .
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Colorectal Cancer: FUT3-driven sLeᵃ/sLeˣ expression promotes metastasis via E-selectin binding .
Cardiovascular and Pulmonary Diseases
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Atherothrombosis: Functional FUT3 polymorphisms (e.g., T59G) increase disease risk (OR = 2.03 in abstainers) .
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Idiopathic Pulmonary Fibrosis (IPF): Genetically elevated FUT3 levels reduce IPF risk (OR = 0.76, 95% CI: 0.68–0.86) .
Infectious and Inflammatory Disorders
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Norovirus Susceptibility: FUT3 variants influence attachment to histo-blood group antigens .
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Ulcerative Colitis: Polymorphisms in FUT3 correlate with disease severity .
Common SNPs and Haplotypes
Lewis-Negative Phenotype
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~10.8% of individuals with FUT3 loss-of-function mutations lack Lewis antigens on erythrocytes .
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Associated with reduced bacterial adhesion but increased cardiovascular risk .
Diagnostic Markers
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Cancer Biomarkers: sLeᵃ/sLeˣ antigens are prognostic in pancreatic and gastric cancers .
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Blood Typing: Lewis antigen status predicts transfusion compatibility .
Therapeutic Targeting
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Antisense Oligonucleotides: Inhibit FUT3 to reduce metastasis in colon carcinoma .
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Small-Molecule Inhibitors: Talniflumate suppresses GCNT3 (a related glycoenzyme), reducing tumor migration .
Mendelian Randomization Studies
CRISPR/Cas9 Models
Table 1: FUT3 in Cancer Progression
| Study Model | Key Result | Reference |
|---|---|---|
| Capan-1 (Pancreatic) | FUT3 knockdown reduces tumor volume by 97.8% | |
| HPAF-II (Pancreatic) | FUT3 silencing downregulates β-catenin/MUC4 |
Table 2: Clinical Associations of FUT3 SNPs
Product Specs
Product Science Overview
FUT3 was first cloned among the members of the α1,3-fucosyltransferase (α1,3FUT) family by Kukowska-Latallo et al. in 1990 . It was named Fuc-TIII by J. Lowe et al. or FUT3 by Oriol et al. Later, it was demonstrated to be the Lewis enzyme responsible for the expression of Lewis histo-blood group antigens, such as Lewis a (Lea) and Lewis b (Leb) .
FUT3 catalyzes the transfer of fucose from GDP-fucose to the N-acetylglucosamine (GlcNAc) residue of type-2 chain (Galβ1-4GlcNAc) with an α1,3-linkage, or to the GlcNAc residue of type-1 chain (Galβ1-3GlcNAc) with an α1,4-linkage . This enzymatic activity is essential for the biosynthesis of various Lewis antigen epitopes, including Lea, Leb, Lex, Ley, sialyl Lea (sLea), and sLex .
The Lewis antigens synthesized by FUT3 are involved in several biological processes:
- Cell-Cell Adhesion: Lewis antigens facilitate cell-cell interactions, which are crucial for tissue formation and maintenance.
- Immune Response: These antigens play a role in the immune system by mediating interactions between cells and pathogens.
- Signal Transduction: Lewis antigens are involved in signaling pathways that regulate various cellular functions.
Recombinant Human Fucosyltransferase 3 (FUT3) is produced using advanced biotechnological methods. It is formulated to be used in cell surface glycoengineering of living cells without affecting cell viability or native phenotype . The recombinant protein is typically supplied as a carrier-free solution, ensuring high purity and stability .
Recombinant FUT3 has several applications in research and biotechnology:
- Glycoengineering: Used to modify the glycosylation patterns on cell surfaces, which can be important for studying cell interactions and developing therapeutic strategies.
- Biochemical Studies: Helps in understanding the enzymatic mechanisms and substrate specificities of fucosyltransferases.
- Clinical Research: Investigated for its potential role in disease mechanisms and as a target for therapeutic interventions.
