ABCG2

An article about the ABCG2 protein

ABCG2

ABCG2 protein embedded in the plasma membrane

ABCG2, also known as the ATP-binding cassette sub-family G member 2, is a protein that in humans is encoded by the ABCG2 gene. It is a member of the ATP-binding cassette (ABC) transporter family, which is involved in the transport of various molecules across extra- and intracellular membranes.

Structure

ABCG2 is a half-transporter, meaning it consists of a single transmembrane domain and a single nucleotide-binding domain. It functions as a homodimer, with two identical ABCG2 proteins associating to form a functional transporter. The protein is embedded in the plasma membrane, where it plays a crucial role in the efflux of substrates out of the cell.

Function

ABCG2 is known for its role in the multidrug resistance phenomenon, where it actively transports a variety of drugs and xenobiotics out of cells, thereby reducing their intracellular concentrations. This function is particularly important in cancer cells, where overexpression of ABCG2 can lead to resistance to chemotherapy drugs.

In addition to its role in drug resistance, ABCG2 is involved in the transport of physiological substrates, including heme, porphyrins, and steroid hormones. It is expressed in various tissues, including the liver, intestine, placenta, and blood-brain barrier, where it contributes to the protection of tissues from toxic substances.

Clinical significance

Mutations in the ABCG2 gene can lead to altered function of the protein, which may result in various clinical conditions. For example, certain polymorphisms in ABCG2 are associated with increased risk of gout, due to impaired excretion of uric acid.

ABCG2 is also a target for overcoming drug resistance in cancer therapy. Inhibitors of ABCG2 are being investigated as potential adjuvants to chemotherapy, aiming to increase the effectiveness of anticancer drugs by preventing their efflux from cancer cells.

Research

Ongoing research is focused on understanding the detailed mechanisms of substrate recognition and transport by ABCG2, as well as its regulation and expression in different tissues. Structural studies using techniques such as X-ray crystallography and cryogenic electron microscopy are providing insights into the conformational changes that occur during the transport cycle.

Related pages

• ATP-binding cassette transporter
• Multidrug resistance
• Cancer therapy
• Drug metabolism