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FEBS Lett. 2017 Jan;591(1):47-55. doi: 10.1002/1873-3468.12525. Epub 2017 Jan 1.

Role of spacer-1 in the maturation and function of GlcNAc-1-phosphotransferase.

Author information

1
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Abstract

The UDP-GlcNAc:lysosomal enzyme, N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-PT), is an α2 β2 γ2 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, GlcNAc-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 GlcNAc-1-PT, we suggest renaming `spacer-1' the `regulatory-1' domain.

KEYWORDS:

GlcNAc-1-phosphotransferase; lysosomal enzyme; mannose 6-phosphate; site-1 protease; spacer domain

PMID:
27981560
PMCID:
PMC5235957
DOI:
10.1002/1873-3468.12525
[Indexed for MEDLINE]
Free PMC Article

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