Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member: comparative mapping of the locus for the human peptide antibiotic FALL-39.

Abstract

PR-39 is a porcine 39-aa peptide antibiotic composed of 49% proline and 24% arginine, with an activity against Gram-negative bacteria comparable to that of tetracycline. In Escherichia coli, it inhibits DNA and protein synthesis. PR-39 was originally isolated from pig small intestine, but subsequent cDNA cloning showed that the gene is expressed in the bone marrow. The open reading frame of the clone showed that PR-39 is made as 173-aa precursor whose proregion belongs to the cathelin family. The PR39 gene, which is rather compact and spans only 1784 bp has now been sequenced. The coding information is split into four exons. The first exon contains the signal sequence of 29 residues and the first 37 residues of the cathelin propart. Exons 2 and 3 contain only cathelin information, while exon 4 codes for the four C-terminal cathelin residues and the mature PR-39 peptide extended by three residues. The sequenced upstream region (1183 bp) contains four potential recognition sites for NF-IL6 and three for APRF, transcription factors known to regulate genes for both cytokines and acute phase response factors. Genomic hybridizations revealed a fairly high level of restriction fragment length polymorphism and indicated that there are at least two copies of the PR39 gene in the pig genome. PR39 was mapped to pig chromosome 13 by linkage and in situ hybridization mapping. The gene for the human peptide antibiotic FALL-39 (also a member of the cathelin family) was mapped to human chromosome 3, which is homologous to pig chromosome 13.

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

“…Gene structures for cathelicidins, as exemplified by PR-39, protegrins, and prophenins, are all compact and organized in the same manner with four exons and three introns [46,137,138] (Fig. 4).…”

cDNA sequences of three sheep myeloid cathelicidins

“…Comparison of the nucleotide sequences (not shown) shows 90% identity in the 5' pre-proregions (nt 1-390), 83% with a two gap insertion in the sequences corresponding to the antimicrobial domain (nt 391-570) and 93% in the 3' non-coding regions (nt 571-807). The high level of identity suggests that the ovine and bovine precursors are derived from a common ancestor gene, from which the precursor of porcine PR-39 [10,38] may also have originated. Also, a decreased nucleotide identity in the region encompassing nt 391 570 indicates that the rate of mutation in the se- Fig.…”

Structures of genes for two cathelin‐associated antimicrobial peptides: prophenin‐2 and PR‐39

“…Fax: (1) (310) 206 8766. E-mail: rlehrer@medicine.medsch.ucla.edu Sequence data have been deposited with EMBL/GenBank Libraries with the following accession numbers X89201 S. scrofa flPR-39 gene, X89202 S. scrofa PF-2 gene To date, only genes for porcine protegrins and PR-39 have been described [25,26]. We now report the structures of genes for prophenin-2 (PF-2) and a variant form of PR-39.…”