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Role of spacer‐1 in the maturation and function of Glc NA c‐1‐phosphotransferase
Author(s) -
Liu Lin,
Lee WangSik,
Doray Balraj,
Kornfeld Stuart
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12525
Subject(s) - phosphorylation , chemistry , biochemistry , mannose 6 phosphate , golgi apparatus , mannose , lysosome , cleavage (geology) , phosphotransferase , random hexamer , enzyme , biology , endoplasmic reticulum , paleontology , receptor , growth factor , fracture (geology)
The UDP ‐Glc NA c:lysosomal enzyme, N ‐acetylglucosamine‐1‐phosphotransferase (Glc NA c‐1‐ PT ), is an α 2 β 2 γ 2 hexamer that mediates the initial step in the formation of the mannose 6‐phosphate targeting signal on newly synthesized lysosomal acid hydrolases. The GNPTAB gene encodes the 1256 amino acid long α/β precursor which is normally cleaved at K928 in the early Golgi by Site‐1 protease (S1P). Here, we show that removal of the so‐called ‘spacer‐1′ domain (residues 86–322) results in cleavage almost exclusively at a second S1P consensus sequence located upstream of K928. In addition, Glc NA c‐1‐ PT lacking spacer‐1 exhibits enhanced phosphorylation of several non‐lysosomal glycoproteins, while the phosphorylation of lysosomal acid hydrolases is not altered. In view of these effects on the maturation and function of Glc NA c‐1‐ PT , we suggest renaming `spacer‐1′ the `regulatory‐1′ domain.