Amino acid sequence of the nonsecretory ribonuclease of human urine.
The amino acid sequence of a nonsecretory ribonuclease isolated from human urine was determined except for the identity of the residue at position 7. Sequence information indicates that the ribonucleases of human liver and spleen and an eosinophil-derived neurotoxin are identical or very closely related gene products. The sequence is identical at about 30% of the amino acid positions with those of all of the secreted mammalian ribonucleases for which information is available. Identical residues include active-site residues histidine-12, histidine-119, and lysine-41, other residues known to be important for substrate binding and catalytic activity, and all eight half-cystine residues common to these enzymes. Major differences include a deletion of six residues in the (so-called) S-peptide loop, insertions of two, and nine residues, respectively, in three other external loops of the molecule, and an addition of three residues at the amino terminus. The sequence shows the human nonsecretory ribonuclease to belong to the same ribonuclease superfamily as the mammalian secretory ribonucleases, turtle pancreatic ribonuclease, and human angiogenin. Sequence data suggest that a gene duplication occurred in an ancient vertebrate ancestor; one branch led to the nonsecretory ribonuclease, while the other branch led to a second duplication, with one line leading to the secretory ribonucleases (in mammals) and the second line leading to pancreatic ribonuclease in turtle and an angiogenic factor in mammals (human angiogenin). The nonsecretory ribonuclease has five short carbohydrate chains attached via asparagine residues at the surface of the molecule; these chains may have been shortened by exoglycosidase action.(ABSTRACT TRUNCATED AT 250 WORDS)
Beintema
J J
JJ
Biochemisch Laboratorium, Rijksuniversiteit, Groningen, The Netherlands.
Hofsteenge
J
J
Iwama
M
M
Morita
T
T
Ohgi
K
K
Irie
M
M
Sugiyama
R H
RH
Schieven
G L
GL
Dekker
C A
CA
Glitz
D G
DG
D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D004722:Endoribonucleases / Q000652:urine*; D006801:Humans; D007525:Isoelectric Focusing; D008969:Molecular Sequence Data
D004722:Endoribonucleases; C029494:ribonuclease U