Stein C, Gieselmann V, Kreysing J, Schmidt B, Pohlmann R, Waheed A, Meyer H E, O'Brien J S, von Figura K
Biochemie II, Universität Göttingen, Federal Republic of Germany.
J Biol Chem. 1989 Jan 15;264(2):1252-9.
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.
克隆并测序了人芳基硫酸酯酶A的全长cDNA。预测的氨基酸序列包含507个残基。18个残基的假定信号肽之后是胎盘芳基硫酸酯酶A的NH2末端序列。其中一个芳基硫酸酯酶A肽在预测的COOH末端之前3个残基处结束。这表明芳基硫酸酯酶A的蛋白水解加工仅限于信号肽的切割。预测序列包含三个潜在的N-糖基化位点，其中两个可能被利用。该序列与溶酶体酶的任何已知序列均无同源性，但与人类类固醇硫酸酯酶有35%的同一性。转染猴肾细胞和幼仓鼠肾细胞导致芳基硫酸酯酶A活性增加高达200倍。芳基硫酸酯酶A位于溶酶体样结构中，并以依赖甘露糖6-磷酸受体的方式转运至致密溶酶体。芳基硫酸酯酶A cDNA与来自人成纤维细胞和人肝脏的RNA中的2.0和3.9千碱基种类杂交。在两名患者的异染性脑白质营养不良成纤维细胞中检测到大小相似的RNA种类，其中芳基硫酸酯酶A多肽的合成要么可检测到，要么不存在。
