FUT2

FUT2 (fucosyltransferase 2) is a protein-encoding gene; it instructs the organism to create an enzyme called Galactoside 2-alpha-L-fucosyltransferase 2.

With a functional FUT2 gene, a person becomes a secretor. Secreted in their saliva and mucus is a soluble form of the H-antigen, which can allow the person to have a proper ABO blood type depending on their genetics. [R]

A person can be either a secretor or a nonsecretor depending on whether the person secretes their blood type antigens into the body fluids, such as saliva, mucus (in the digestive tract and the respiratory cavities), tears, sweat, etc.

The determination of secretor status is important because secretor status is associated with a wide variety of diseases (like urinary tract infections, diabetes, digestive disorders, etc.).

Mediates the transfer of fucose to the terminal galactose on glycan chains of cell surface glycoproteins and glycolipids (PubMed:7876235). The resulting epitope plays a role in cell-cell interaction including host-microbe interaction (PubMed:12692541, PubMed:8018146). Mediates interaction with intestinal microbiota influencing its composition (PubMed:21625510, PubMed:24733310, PubMed:22068912). Creates a soluble precursor oligosaccharide FuC-alpha ((1,2)Galbeta-) called the H antigen which is an essential substrate for the final step in the soluble ABO blood group antigen synthesis pathway (PubMed:7876235).

Specific types of cells that line the surface of our organs and blood vessels (epithelial cells) secrete a protein that then latches onto our red blood cells.  This protein is called a Lewis antigen.

Lewis antigens are also found on the surface of the kidney, genitals, and gastrointestinal area. FUT2 encodes an enzyme (-1,2 fucosyltransferase) which regulates which kind of antigen will be secreted (R).

The enzymes created by FUT2 allow for the addition of fucose in -1,2-linkage to the galactose of type 1 (Gal²1,3GlcNAc-R) and type 2 Gal²1,4GlcNAc- R) disaccharide to form H-type 1 and H-type 2 antigens, respectively (R).

The individual who is a so-called secretor has AB blood group antigen in the saliva and other body fluids; the nonsecretor does not (R).

Background

Blood Groups and Antigens: While most people are familiar with the idea of the ABO blood type, there are many more distinguishing factors between the blood types of different people. The options of A, B, AB, and O comprise one blood group, whereas the Rh factor (+ or -) show another blood group. Scientists have identified 35 such blood groups so far, due to the presence of various kinds of antigens in the blood.

Antigens are molecules in the blood that trigger an immune system response, and usually cause health problems for people who receive them. The receptors for these antigens are called antibodies. On red blood cells, the A and B antigens sit on the surface of the cells. They determine ABO blood type. For example, a person with Blood type A has A antigens, and B antibodies. If that person received B-type blood, then their B-antibodies would be triggered and the body would reject the blood. The O blood type does not have any antigens, so any person can receive that blood, no matter which antibodies they have. Similarly, the AB blood type has no A or B antibodies, so they can receive from all blood types. Taking into account + and -, the compatibilities change slightly.

FUT2

FUT2, short for fucosyltransferase 2, is a protein-encoding gene, meaning it instructs the organism to create a certain protein that is used in bodily function. The protein in question is an enzyme called Galactoside 2-alpha-L-fucosyltransferase 2.

With a functional FUT2 gene, a person becomes a secretor. Secreted in their saliva and mucus is a soluble form of the H-antigen, which can allow the person to have a proper ABO blood type depending on their genetics. [R]

Lewis Blood Group Another blood group of interest is the Lewis Blood Group, which deals with the Lea and Leb antigens, pictured below. This process is affected by two genes – the Lewis gene, or FUT3, and of course the Secretor gene, or FUT2. The dominant forms of these genes are usually labelled Le and Se respectively.

The starting molecule is the precursor shown in the top-most diagram. The encoded enzyme from FUT2 adds the yellow fucose ring onto the precursor, creating the middle-left molecule (see the Se arrow). The enzyme from the other gene, FUT3, adds the bright green fucose ring onto the molecule. With just the bright green ring from FUT3, the molecule is an Lea antigen. When FUT2 takes effect as well, an Leb is formed.

Because Lea is converted into Leb quite efficiently, there is very little Lea antigen in people who secrete. Similarly, people who do not secrete do not have a working FUT2 enzyme, meaning they have no Leb. Scientists and medical practitioners take advantage of this phenomenon in checking whether a person is a secretor or non-secretor – those with a detectable amount of Lea antigen are non-secretors, and everyone else is a secretor. [R]

Secretion vs Non-Secretion

Secretion The secretion status refers to an individual’s ability to secrete their ABO antigens into their bodily fluids, such as saliva or the mucus in the gastrointestinal tract. The FUT2 gene allows for secretion to occur [R].

Studies demonstrate that about 20% of those with European ancestry are non-secretors, while the other 80% are secretors. [R]

The Encoded Protein

The protein that results from this gene is the galactoside 2-L-fucosyltransferase enzyme. The “fucosyl-transferase” portion of the name indicates its purpose: transferring a fucose ( a blood-typetype of sugar) molecule from one place to another.

ABO and Bombay Blood Groups As aforementioned, there are 35 blood group classifications, including ABO and Rh. An extremely rare blood group, the Bombay group, is closely related to FUT2. [R]

There are two important genes here – the H gene (FUT1) and the Secretor gene (FUT2). The H antigen (or substance H) is shown on the surface of the O-type blood cell.

FUT1 (in its dominant form) encodes for the enzyme that catalyzes the last step in creating the H-antigen. This same H antigen is a precursor to the A and B antigens; as shown in the diagram, adding a purple N acetyl-galactosamine ring turns the H into an A antigen, while adding a brown Galactose ring turns H into a B antigen.

An individual with the recessive form of FUT1 will instead have the (lower case) h-antigen present on their blood cells, which does not immediately turn into any of the ABO blood types. This creates a phenomenon where a person with this hh blood typecan donate blood to anyone (as their blood “lacks” antigens).

Unfortunately, they produce A, B, and H antibodies, and cannot receive blood from anyone other than those with the Bombay blood type. While this is only present in about 0.0004% of the human population, it presents a unique healthcare problem when it comes to transfusions, as Bombay blood type is usually misdetected as O-blood-type.

     From NCBI Gene: Vitamin b12 plasma level quantitative trait locus 1

     From NCBI Gene: The protein encoded by this gene is a Golgi stack membrane protein that is involved in the creation of a precursor of the H antigen, which is required for the final step in the soluble A and B antigen synthesis pathway. This gene is one of two encoding the galactoside 2-L-fucosyltransferase enzyme. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008] From UniProt: Creates a soluble precursor oligosaccharide FuC-alpha ((1,2)Galbeta-) called the H antigen which is an essential substrate for the final step in the soluble A and B antigen synthesis pathway. H and Se enzymes fucosylate the same acceptor substrates but exhibit different Km values.

Non-secretors have lower levels of bifidobacteria and would benefit from probiotics.

• Probiotics (Now-100 billion) 

Estrogen increases FUT2 expression (R).