The cellular processes regulating the turnover of ABCA1 protein have only. This chapter will describe function and expression of several ABC transporters (such as P-GP, BCRP, and MRPs), their substrates and inhibitors, as well as their clinical significance.ĪBC gene-related disease Breast cancer resistance protein Multidrug resistance Multidrug resistance-associated proteins P-glycoprotein. ATP-binding cassette transporter A1 (ABCA1) plays a major role in cholesterol. Several human diseases such as cystic fibrosis, sitosterolemia, Tangier disease, intrahepatic cholestasis, and retinal degeneration are associated with mutations in corresponding transporters. The ABC transporters are the largest familyof transmembrane proteins, with seven subfamilies that are designated A to G on the basis of sequence and structural homology, and are responsible. Some ABC transporters are also involved in diverse cellular processes such as maintenance of osmotic homeostasis, antigen processing, cell division, immunity, cholesterol, and lipid trafficking. These ABC transporters are expressed in various tissues such as the liver, intestine, kidney, and brain, playing important roles in absorption, distribution, and excretion of drugs. Of them, at least 11 ABC transporters including P-glycoprotein (P-GP/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) are involved in multidrug resistance (MDR) development. In eukaryotes, ABC transporters are expressed in plasma. More than 40 ABC transporters have been identified in human, which are divided into 7 subfamilies (ABCA to ABCG) based on their gene structure, amino acid sequence, domain organization, and phylogenetic analysis. These proteins are classified according to the sequence and organization of their ABC domain(s) 1. One of the largest transporter families is the ATP-binding cassette (ABC) family. ABC transporters are typically single polypeptide chains that consist of a transmembrane domain (TMD), a nucleotide-binding domain (NBD), followed by another TMD and NBD (see chapter, ABC Transporters: An Overview ). Typically, an ABC transporter is composed of four parts: two membrane-integral domains each of which spans the membrane six times, and two ATP-hydrolyzing. 5 This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis. They translocate their substrates either in or out of the cells, by serving as importers and exporters, respectively. The processes are usually mediated by specific transporters. ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the cholesterol efflux regulatory protein (CERP) is a protein which in humans is encoded by the ABCA1 gene. ABC transporter family ATP-binding cassette (ABC) transporters are a large and ubiquitous superfamily of proteins in all living organisms from microbes to humans. The transport of specific molecules across lipid membranes is an essential function of all living organisms.
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