Adenosine triphosphate (ATP)-binding cassette (ATP) transporters are transmembrane proteins that function to transport many substrates across membranes and ensure the fidelity of transcription and translation in an ATP-dependent manner (Jones & Giorgio, 2004). These transporters can carry out their functions because information that defines their roles is contained within molecular sequences. Such information is usually in the form of motifs and is found in certain regions of the respective molecular sequences known as domains. These motifs are usually conserved (Bork & Koonin, 1996), and such understanding becomes important in many research areas. One of the research interests concerns the development of new treatments against the multidrug-resistant property of ABC transporters in the treatment of relevant human diseases such as cystic fibrosis and Tangier disease (Stefková et al., 2004). With each of these new applications, substantial knowledge of sequence motifs in terms of their functional significance is required. In this essay, discussion is limited to protein sequence signatures in the nucleotide-binding domains (NBDs) of ABC transporters related to substrate translocation. It will be seen that protein sequence motifs perform a similar function between species and any mutation can affect its overall function. However, it should also be noted that these motifs may cause slightly different mechanisms in different species and that they may perform their function in certain domains of the protein. Understanding protein sequence signatures must be introduced before evaluating their functional significance. . Protein sequences are one-dimensional strings of amino acid letter codes that represent the ... center of paper ......er motif B in the N-terminal nucleotide-binding domain (NBD-1) of Cdr1p of Candida albicans ha acquired a new role in the hydrolysis of ATP. Biochemistry, 45(49): 14726.Schmees, G., Stein, A., Hunke, S., Landmesser, H., & Schneider, E. (1999). Functional consequences of mutations in the conserved “signature sequence” of the ATP-binding cassette protein MalK. Eur J Biochem, 266(2): 420-430. Stefková, J., Poledne, R., & Hubácek, J. A. (2004). ATP-binding cassette (ABC) transporters in human metabolism and disease. Physiological Research / Academia Scientiarum Bohemoslovaca, 53(3): 235.Tanabe, K., Lamping, E., Nagi, M., Okawada, A., Holmes, AR, Miyazaki, Y., Cannon, R.D., Monk, B.C. , & Niimi, M. (2011). Candida albicans Cdr1p and Cdr2p chimeras reveal features of pleiotropic drug resistance transporter structure and function. Molecular microbiology, 82(2): 416-433.