Eosinophil cationic protein cDNA. Comparison with other toxic cationic proteins and ribonucleases.
Human eosinophil granules contain several basic proteins including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and major basic protein (MBP). ECP and MBP are potent helminthotoxins while EDN is less so. Both ECP and EDN possess neurotoxic and ribonuclease activities. A clone representing ECP mRNA was isolated from an eosinophil lambda ZAP cDNA library. The cDNA sequence codes for a preprotein of 160 amino acids and a protein of 133 amino acids, the amino terminus of which is identical to the known partial amino acid sequence of ECP. The ECP nucleotide sequence shows similarity to EDN, rat pancreatic ribonuclease, and human angiogenin; all are members of the ribonuclease gene superfamily. Although the deduced amino acid sequence of ECP shares identical active site and substrate binding site residues with EDN, angiogenin, and human pancreatic ribonuclease, the ribonuclease activity of ECP is 50 to 100 times less than that of EDN possibly because of the lack of a positively charged residue at human pancreatic ribonuclease position 122. The calculated isoelectric point (10.8), electronic charge (14.5), and cationic charge distribution of ECP are different from those of EDN but similar to those of MBP, which may account in part for the greater helminthotoxic activity of ECP when compared to EDN. These data suggest that ECP and EDN are derived from a common ancestral ribonuclease gene and that ECP has evolved into a potent helminthotoxin similar in some respects to MBP, while losing much of its ribonuclease activity.
Barker
R L
RL
Department of Immunology, Mayo Medical School, Rochester, MN 55905.
Loegering
D A
DA
Ten
R M
RM
Hamann
K J
KJ
Pease
L R
LR
Gleich
G J
GJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics* / Q000302:isolation & purification; D003603:Cytotoxins / Q000235:genetics* / Q000302:isolation & purification; D004247:DNA / Q000302:isolation & purification*; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000235:genetics / Q000302:isolation & purification; D011487:Protein Conformation; D012260:Ribonucleases / Q000235:genetics* / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid
D001798:Blood Proteins; D003603:Cytotoxins; D047091:Eosinophil Granule Proteins; D009498:Neurotoxins; D004247:DNA; D012260:Ribonucleases