Sequence, organization, chromosomal localization, and alternative splicingof the human serine protease inhibitor gene hurpin (PI13) which is upregulated in psoriasis

Hurpin (protease inhibitor 13; PI13) is the most recently identified member of the ovalbumin family of serine protease inhibitors (serpins). It is exp ressed in human epidermal keratinocytes and is downregulated by exposure to ultraviolet irradiation. A role for hurpin in the proliferation or differe ntiation of keratinocytes has been proposed because of its strong expressio n in proliferating cells and its deregulated expression in the lesional epi dermis of psoriatic patients. Here, we report the cloning, chromosomal loca lization, and complete sequence of the human hurpin gene. By PCR-based scre ening of the GeneBridge 4 radiation hybrid panel, we mapped the gene to chr omosome 18q21.3, close to a known cluster of ov-serpin genes. Using the ful l-length cDNA for hurpin, we identified two clones from an arrayed genomic pi placental library that contain the entire hurpin gene, Sequencing reveal ed that the gene covers 12.253 kb and is comprised of eight exons and seven introns, The exon-intron boundaries are identical in position and phasing to those in other members of the 18q serpin gene cluster, and analysis of h urpin variants indicated that modified functional inhibitors, differing onl y in the CD interhelical loop, can be generated by differential splicing of exon 3. These data show that hurpin is a typical member of the 18q ovalbum in-serpins most closely related to the serpins squamous-cell carcinoma anti gens 1 and 2.