N-acetylglucosamine-1-phosphotransferase subunits alpha/beta
EC=2.7.8.17
Alternative name(s):
GlcNAc-1-phosphotransferase subunits alpha/beta
Stealth protein GNPTAB
UDP-N-acetylglucosamine-1-phosphotransferase subunits alpha/beta
Cleaved into the following 2 chains:
N-acetylglucosamine-1-phosphotransferase subunit alpha
N-acetylglucosamine-1-phosphotransferase subunit beta
Gene names
Name: GNPTAB
Synonyms: GNPTA, KIAA1208
Function
Catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. M6P residues are required to bind to the M6P receptors (MPR), which mediate the vesicular transport of lysosomal enzymes to the endosomal/prelysosomal compartment. Ref.8 Ref.10 Ref.23
Catalytic activity
UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose = UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl-phospho-D-mannose. Ref.10
Subunit structure
Hexamer of two alpha, two beta and two gamma (GNPTG) subunits; disulfide-linked. The alpha and/or the beta subunits of the enzyme constitute the catalytic subunits. Ref.10
Subcellular location
N-acetylglucosamine-1-phosphotransferase subunit alpha: Golgi apparatus membrane; Single-pass type I membrane protein Ref.1 Ref.2 Ref.11 Ref.22 Ref.23.
N-acetylglucosamine-1-phosphotransferase subunit beta: Golgi apparatus membrane; Single-pass type II membrane protein.
Tissue specificity
Expressed in the heart, whole brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Ref.2
Domain
The DMAP-interaction domain mediates substrate recognition. It specifically recognizes a conformation-dependent protein determinant present in acid hydrolases (Ref.23).
Post-translational modification
The alpha- and beta-subunits are generated by a proteolytic cleavage by MBTPS1 protease at the Lys-928-Asp-929 bond (Ref.11).
Involvement in disease
Mucolipidosis type II (MLII) [MIM:252500]: Fatal, autosomal recessive, lysosomal storage disorder characterized by severe clinical and radiologic features, peculiar fibroblast inclusions, and no excessive mucopolysacchariduria. Congenital dislocation of the hip, thoracic deformities, hernia, and hyperplastic gums are evident soon after birth.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23
Mucolipidosis type III complementation group A (MLIIIA) [MIM:252600]: Autosomal recessive disease of lysosomal enzyme targeting. Clinically MLIII is characterized by restricted joint mobility, skeletal dysplasia, and short stature. Mildly coarsened facial features and thickening of the skin have been described. Cardiac valvular disease and corneal clouding may also occur. Half of the reported patients show learning disabilities or mental retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22
Miscellaneous
Due to the low pH in the endosomal/prelysosomal compartment, the lysosomal enzyme-MPR complex dissociates and then the enzyme is delivered to the lysosome. Between 5% and 20% of newly synthesized lysosomal enzymes escape the binding to the MPR in the Golgi apparatus and are secreted.
Stealth proteins are part of a protein family that is conserved from bacteria to higher eukaryotes. Family members were first identified in microbes as proteins that help pathogens to elude the host innate immune system. Microbial stealth proteins are most likely involved in the biosynthesis of exopolysaccharides. Stealth proteins are predicted to function as hexose-1-phosphoryltransferases.
Sequence similarities
Belongs to the stealth family.
Contains 1 DMAP-interaction domain.
Contains 1 EF-hand domain.
Contains 2 LNR (Lin/Notch) repeats.
N-acetylglucosamine-1-phosphotransferase subunit gamma
Alternative name(s):
GlcNAc-1-phosphotransferase subunit gamma
UDP-N-acetylglucosamine-1-phosphotransferase subunit gamma
Gene names
Name: GNPTG
Synonyms: C16orf27, GNPTAG
ORF Names: CAB56184, LP2537
Function
Non-catalytic subunit of the N-acetylglucosamine-1-phosphotransferase complex, an enzyme that catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. Binds and presents the high mannose glycans of the acceptor to the catalytic alpha and beta subunits (GNPTAB). Enhances the rate of N-acetylglucosamine-1-phosphate transfer to the oligosaccharides of acid hydrolase acceptors. Ref.1 Ref.8
Subunit structure
Homodimer; disulfide-linked. Hexamer of two alpha (GNPTAB), two beta (GNPTAB) and two gamma (GNPTG) subunits; disulfide-linked. The alpha and/or the beta subunits of the enzyme constitute the catalytic subunits. Ref.1 Ref.8 Ref.10
Subcellular location
Secreted. Golgi apparatus Ref.10.
Tissue specificity
Widely expressed. Ref.1
Post-translational modification
Cys-245 mediates the formation of the interchain disulfide bond for formation of the homofimer. Cys-142, Cys-157 and Cys-169 are involved in intramolecular disulfide bonds formation By similarity.
Involvement in disease
Mucolipidosis type III complementation group C (MLIIIC) [MIM:252605]: Autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (GlcNAc-phosphotransferase) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Typical clinical findings include stiffness of the hands and shoulders, claw-hand deformity, scoliosis, short stature, coarse facies, and mild mental retardation. Radiographically, severe dysostosis multiplex of the hip is characteristic and frequently disabling. The clinical diagnosis can be confirmed by finding elevated serum lysosomal enzyme levels and/or decreased lysosomal enzyme levels in cultured fibroblasts.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.10 Ref.11
Sequence similarities
Contains 1 PRKCSH domain.
