title: Granzyme-like sequences in bony fish shed light on the emergence of hematopoietic serine proteases during vertebrate evolution.
abstract: Hematopoietic serine proteases (SPs) are stored in the granules of different leukocytes and these enzymes are important effector molecules in the immune system of mammals. However, very little is known about the presence of these proteins in lower vertebrates. Herein, the primary structures of five novel fish SPs, from the Atlantic cod (Gadus morhua) and the channel catfish (Ictalurus punctatus), are presented. One of the cod SPs is a homologue to human GzmA and K. The other fish SPs identified are termed 'Gzm-like' and are distantly related to a large heterogeneous group of hematopoietic SPs, including most of the T-cell Gzms (B-H), the mast cell chymases, the mast cell/basophil proteases of the mouse mast cell protease-8 subfamily (M8-family) and the neutrophil cathepsin G. Extensive BLAST-searches in genome and expressed sequence tag (EST) databases identified 40 additional teleost SPs related to the mammalian hematopoietic SP family. Subsequent phylogenetical analyses clearly demonstrate that the diversification into different subgroups within the GzmB/chymase/cathepsin G-related family has occurred independently in bony fishes and in mammals. In contrast, our findings suggest that the three subgroups, including (1) GzmK and the potent apoptosis-inducing GzmA, (2) the neutrophil proteases (proteinase 3, N-elastase and azurocidin), and (3) adipsin, have all evolved as distinct groups before the separation of tetrapods from the ray-finned fish approximately 420 million years ago.
authors.affiliation: Department of Cell and Molecular Biology, Immunology Programme, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden. sara.wernersson@bmc.uu.se
authors.forename: Sara
authors.initials: S
authors.lastname: Wernersson
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Reimer
authors.forename: Maryam
authors.initials: M
authors.lastname: Poorafshar
authors.forename: Ulrika
authors.initials: U
authors.lastname: Karlson
authors.forename: Niklas
authors.initials: N
authors.lastname: Wermenstam
authors.forename: Eva
authors.initials: E
authors.lastname: Bengtén
authors.forename: Melanie
authors.initials: M
authors.lastname: Wilson
authors.forename: Lars
authors.initials: L
authors.lastname: Pilström
authors.forename: Lars
authors.initials: L
authors.lastname: Hellman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D048389:Gadus morhua / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics*; D007059:Ictaluridae / Q000235:genetics*; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D012697:Serine Endopeptidases