SPXX, a frequent sequence motif in gene regulatory proteins

A new DNA-binding unit, composed of four amino acid residues and common in gene regulatory proteins, is proposed. The occurrences of the sequences Ser-Pro-X-X (SPXX) and Thr-Pro-X-X (TPXX) in gene regulatory proteins are compared with those in general proteins. These sequences are found more frequently in gene regulatory proteins including homoeotic gene products, segmentation gene products, steroid hormone receptors and certain oncogene products, than they are in DNA-binding proteins that are not directly involved in gene regulation, such as the core histones, or in general proteins. It is therefore suggested that these sequences contribute to DNA-binding in a manner important for gene regulation. Amino acid residues characteristic of the types of proteins are found as the variable residues X: basic residues, Lys and Arg, in histones, H1 and sea urchin spermatogenous H2B; Tyr in RNA polymerase II; and Ser, Thr, Ala, Leu and Pro in other gene regulatory proteins S(T)PXX sequences are located on either side of other DNA-recognizing units such as Zn fingers, helix-turn-helices, and cores of histones. The structure of a S(T)PXX sequence is presumed to be a beta-turn I stabilized by two hydrogen bonds, and its potential mode of DNA-binding is discussed.