ATP-binding cassette sub-family G member 2 transporter (ABCG2)

ABCG2 is an ATP-binding cassette transporter that functions as a poly-specific efflux pump, exporting a broad spectrum of drugs and xenobiotics against their concentration gradient by coupling transport to ATP binding and hydrolysis. It is a half-transporter with one nucleotide-binding domain and one transmembrane domain (six helices) that homodimerizes to become functional, exhibiting a reverse TMD–NBD arrangement characteristic of the ABCG subfamily. ABCG2 is expressed at key barrier and excretory sites (e.g., intestine, bile canaliculi, placenta, blood–brain barrier), where it limits absorption, enhances elimination, and protects tissues from toxins. In oncology, overexpression confers multidrug resistance to numerous anticancer agents, including topotecan and SN-38; it also transports newer agents such as rucaparib. Known chemical inhibitors include fumitremorgin C and its analog Ko-143, and some calcium channel blockers (amlodipine, felodipine, nifedipine). Clinically relevant pharmacogenetic variants such as Q141K (c.421C>A) occur at different frequencies among ethnic groups and can alter transporter function and drug pharmacokinetics. Structural studies, increasingly via cryo-EM, have elucidated substrate-binding within a central cavity and clarified oligomeric and domain organization pertinent to rational modulator design.

Other names

Breast cancer resistance protein (BCRP)ABCG2CD338/CDw338ATP-binding cassette super-family G member 2

Efflux transport of substrates across the plasma membrane using ATP binding and hydrolysis, reducing intracellular drug concentrations and contributing to multidrug resistance. Pharmacokinetic modulation at absorption and excretory barriers (e.g., intestine, bile canaliculi, placenta, BBB), affecting bioavailability and tissue exposure of substrates.