Evolution of placentally expressed cathepsins.
Species and strain variants of a family of placentally expressed cathepsins (PECs) were cloned and sequenced in order to identify evolutionary conserved structural characteristics of this large family of cysteine proteases. Cathepsins M, P, Q, and R, are conserved in mice and rats but homologs of these genes are not found in human or rabbit placenta, showing that this family of proteases are probably restricted to rodents. Species-specific gene duplications have given rise to variants of cathepsin M in mice, and cathepsin Q in rats. Although the PECs have diverged at a greater rate than the other lysosomal cathepsins, residues around the specificity sub-sites of the individual enzymes are conserved. Strain-specific polymorphisms show that the evolutionary rate of divergence of cathepsins M and 3, the most recently duplicated pair of mouse genes, is even higher than the other PECs. In human placenta, critical functions of the PECs are probably performed by broader specificity proteases such as cathepsins B and L.
Sol-Church
Katia
K
Laboratory of Clinical Biochemistry, Alfred I duPont Hospital for Children, P.O. Box 269, Wilmington, DE 19899, USA.
Picerno
Gina N
GN
Stabley
Deborah L
DL
Frenck
Jennifer
J
Xing
Sixun
S
Bertenshaw
Greg P
GP
Mason
Robert W
RW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D010920:Placenta / Q000201:enzymology*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics
C035145:ribosomal neutral proteinase; D002403:Cathepsins; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; C404746:cathepsin Q; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse; C534133:Ctsk protein, rat; C034114:cathepsin M