Cloning and expression of human arylsulfatase A.
A full length cDNA for human arylsulfatase A was cloned and sequenced. The predicted amino acid sequence comprises 507 residues. A putative signal peptide of 18 residues is followed by the NH2-terminal sequence of placental arylsulfatase A. One of the arylsulfatase A peptides ends 3 residues ahead of the predicted COOH terminus. This indicates that proteolytic processing of arylsulfatase A is confined to the cleavage of the signal peptide. The predicted sequence contains three potential N-glycosylation sites, two of which are likely to be utilized. The sequence shows no homology to any of the known sequences of lysosomal enzymes but a 35% identity to human steroid sulfatase. Transfection of monkey and baby hamster kidney cells resulted in an up to 200-fold increase of the arylsulfatase A activity. The arylsulfatase A was located in lysosome-like structures and transported to dense lysosomes in a mannose 6-phosphate receptor-dependent manner. The arylsulfatase A cDNA hybridizes to 2.0- and 3.9-kilobase species in RNA from human fibroblasts and human liver. RNA species of similar size were detected in metachromatic leukodystrophy fibroblasts of two patients, in which synthesis of arylsulfatase A polypeptides was either detectable or absent.
Stein
C
C
Biochemie II, Universität Göttingen, Federal Republic of Germany.
Gieselmann
V
V
Kreysing
J
J
Schmidt
B
B
Pohlmann
R
R
Waheed
A
A
Meyer
H E
HE
O'Brien
J S
JS
von Figura
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D005260:Female; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D010957:Plasmids; D011247:Pregnancy; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D015342:DNA Probes; D004247:DNA; D002553:Cerebroside-Sulfatase