Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen.

Abstract

The Ku (p70/p80) autoantigen consists of two phosphoproteins of molecular mass approximately 70,000 and 80,000 forming a macromolecular complex that binds DNA. Autoantibodies from a patient with systemic lupus erythematosus were used to isolate cDNA clones encoding the human approximately 70-kDa Ku antigen (p70) from a lambda gt11 expression library. The deduced amino acid sequence of p70 consisted of 609 amino acid residues and was confirmed by partial amino acid sequencing. The protein contains two acidic domains of 61 residues (31% Glu + Asp) and 19 residues (53% Glu + Asp) that are similar in size and charge to those found in a number of proteins involved in transcriptional activation. The 61-residue acidic region is rich in serine, raising the possibility that its charge might be modulated by phosphorylation. The predicted amino acid sequence also contains two regions with periodic repeats of either leucine alone, or leucine alternating with serine every seventh position. The latter repeat displays sequence and secondary structural similarities with the "leucine zipper" regions of the c-myc and v-myc oncogene products. The p70 antigen does not appear to have extensive sequence homology with the 80-kDa Ku autoantigen based on analysis of RNA blots and immunological criteria. A major antigenic determinant or determinants recognized by human autoantibodies is located near a leucine repeat on the carboxyl-terminal 190 amino acid residues of p70.

• Authors: W H Reeves, Z M Sthoeger
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 264 Issue 9 Pg. 5047-52 (Mar 25 1989) ISSN: 0021-9258 [Print] United States
• PMID: 2466842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Nuclear
• Antigens, Surface
• Autoantigens
• DNA-Binding Proteins
• Epitopes
• DNA
• DNA Helicases
• XRCC5 protein, human
• Xrcc6 protein, human
• Ku Autoantigen

Topics

• Amino Acid Sequence
• Antigens, Nuclear
• Antigens, Surface (genetics, isolation & purification)
• Autoantigens (genetics, isolation & purification)
• Base Sequence
• Blotting, Northern
• Cloning, Molecular
• DNA (isolation & purification)
• DNA Helicases
• DNA-Binding Proteins (genetics, isolation & purification)
• Epitopes (genetics, isolation & purification)
• Humans
• Ku Autoantigen
• Lupus Erythematosus, Systemic (genetics, metabolism)
• Molecular Sequence Data
• Repetitive Sequences, Nucleic Acid
• Sequence Homology, Nucleic Acid