PEDF and the serpins: Phylogeny, sequence conservation, and functional domains

Inductive expression and characterization analysis of Paralichthys olivaceus pigment epithelium-derived factor in a virally infected cell line

“…Gene sizes of PEDFs are much more variable among species as a result of the very variable sizes of their introns ( Fig. 4; [11,33]); however, it is evidenced that the gene size of PEDF is not always correlated directly with genomic size of species. For example, the length of the zebrafish genome is estimated to be about 1700 Mb, about one-half of the entire genome of human (3000 Mb) and mouse (3300 Mb), about four times of the fugu genome (400 Mb), but the corresponding PEDF gene size is about 13.7 kb for zebrafish, 16 kb for human [42], 8 kb for mouse [8], and 2.9 kb for fugu [11], respectively.…”

“…Recent studies showed that RCL in human PEDF was possibly associated with its secretion [40] but was dispensable for its antiangiogenic activity. Structurally, the RCL of human PEDF, like other serpin members, is divided into three functional regions, P1/P1 0 -, P12-, and P11 0 -regions [3,33]; however, there is lesser homology between them at the P12 region than at the P11 0 -region [41]. When compared to mammalian PEDF proteins, fish PEDF also displays a conserved P11 0 -region and a variable P12 0 -region.…”

“…3). Actually, the RCL region varies considerably for its homology and length among the species [33], generally with over 50% homology between the RCLs of human PEDF and of other mammals and below 50% for other vertebrates including fish PEDFs.…”

“…Apart from the conserved N-glycosylated site at Asn 273 (Asn 285 in human PEDF) [33], there is another predicted site at -N 191 PS-only predicted in PoPEDF but not in any other known PEDF protein, including zebrafish and fugu PEDF proteins. Like other PEDF proteins, PoPEDF should be a secreted protein, since it has a putative signal peptide in the first N-terminal 19 aa (Fig.…”

“…3). Throughout the sequence of PoPEDF protein, the typically conserved clusters of amino acid residues were found at the same position as known mammalian PEDF proteins, including the Cys 249 (residue 261 in human PEDF) [33], the Asp 288 (residue 300 in human PEDF) for binding to collagen [34], a 34 mer fragment (sequence 44-77 in human PEDF) for full antiangiogenic properties [35], a 44-mer fragment (sequence 78-121 in human PEDF) for neuroprotective activity [5], a P11 0 -region, and -N 273 MT-for a N-glycosylated site [33]. Additionally, a conserved serpin motif (…”