The Ku protein is localized in the nucleus and is composed of subunits referred to as Ku-70 (p70) and Ku-86 (p86) which is also known by the synonym Ku-80 or (p80). Ku was first described as an autoantigen to which antibodies were produced in a patient with scleroderma polymyositis overlap syndrome, and was later found in the sera of patients with other rheumatic diseases. Both subunits of the Ku protein have been cloned, and a number of functions have been proposed for Ku, including cell signaling, DNA replication and transcriptional activation. Ku is involved in Pol II-directed transcription by virtue of its DNA binding activity, serving as the regulatory component of the DNA-associated protein kinase that phosphorylates Pol II and transcription factor Sp. Ku proteins also activate transcription from the U1 small nuclear RNA and the human transferrin receptor gene promoters. A Ku-related protein designated the enhancer 1 binding factor (E1BF), composed of two subunits, has been identified as a positive regulator of RNA polymerase I transcription initiation.