Pur-alpha is a protein that in humans is encoded by the PURA gene located at chromosome 5, band q31. Pur-alpha an ancient, multi-functional DNA- and RNA-binding protein. PURA is expressed in every human tissue, where it exists as a protein of 322 amino acids. According to convention, PURA, the gene, is written italicized in all upper case letters. Pur-alpha, the protein, is written with the first letter capitalized and can be found listed as Pur-alpha, Pur-α, Pura, Puralpha, Pur alpha and Pur1. Evolutionary conservation and function Pur-alpha was the first sequence-specific single-stranded DNA-binding protein to be discovered in higher organisms (GenBank M96684.1; GI:190749). It binds to both single-stranded and double-stranded DNA, making contact with G residues in the purine-rich strand of its binding site. Cumulative data shows that Pur-alpha preferentially binds to the sequence (G2-4N1-3)n, where N is not G. N denotes a nucleotide, and n denotes the number of repeats of this small sequence. N may be repeated up to three times in this sequence. Following the identification of a Pur factor, which specifically bound a purine-rich sequence in the control region of the c-MYC gene, the gene, PURA, encoding the protein, Pur-alpha, was cloned and sequenced for both human and mouse (GenBank U02098.1). Pur-alpha belongs to the four-member Pur protein family, which also includes Pur-beta (GenBank AY039216.1; GI:14906267) and two forms of Pur–gamma (Variant A, GenBank AF195513.2; Variant B, GenBank AY077841). Pur protein sequences from bacteria through humans contain an amino acid segment that is strongly conserved (see NCBI smart00712). Human Pur-alpha contains three repeats of this Pur domain and bacterial Pur-alpha contains one. This evolutionary conservation means that the specific sequence of this domain is important for the survival of most species throughout the spectrum of living organisms. This essential nature of the Pur domain piques interest because the functions of Pur-alpha in lower organisms and in humans differ greatly. For example, Pur-alpha is essential for brain and blood cell development in mammals, but bacteria have no brain and no blood. In humans Pur-alpha functions to activate transcription in the nucleus, to facilitate RNA transport in the cytoplasm and to regulate DNA replication in the cell cycle. In certain functions Pur-alpha interacts with family member Pur-beta. Several cell cycle regulatory functions may be mediated by Pur-alpha binding to Cyclin/Cdk protein kinases, which phosphorylate proteins regulating cell cycle transition points. Requirements for Pur-alpha in all organisms are united