Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4.
We used the polymerase chain reaction to identify a mouse cDNA which represented a new member of a growing class of mammalian endoproteases homologous to the yeast Kex2 protease involved in the processing of precursor proteins. This cDNA encoded a 915-residue protein, designated as PC6, containing a subtilisin-like catalytic domain closely related to those of other Kex2-like members (furin, PC2, PC1/3, PC4, and PACE4). It exhibited striking sequence similarity to PACE4 and contained similar protein domains, such as the COOH-terminal Cys-rich region. Northern blot analysis revealed that PC6 mRNA, as with furin and PACE4 mRNAs, was expressed in various tissues and cell lines, with the highest level in the intestine. Transfection experiments revealed that PC6 was capable of cleaving precursors at dibasic sites. These observations suggest that PC6 is a candidate for a processing endoprotease responsible for the maturation of gastrointestinal peptides.
Nakagawa
T
T
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki.
Hosaka
M
M
Torii
S
S
Watanabe
T
T
Murakami
K
K
Nakayama
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D004247:DNA; D006801:Humans; D007422:Intestines / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013381:Subtilisins; D014162:Transfection
D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C080654:PCSK6 protein, human; C513086:Pcsk6 protein, mouse; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae