Human Gene GNPTAB (ENST00000299314.12) Description and Page Index

Comments and Description Text from UniProtKB


	ID: GNPTA_HUMAN DESCRIPTION: RecName: Full=N-acetylglucosamine-1-phosphotransferase subunits alpha/beta; EC=2.7.8.17; AltName: Full=GlcNAc-1-phosphotransferase subunits alpha/beta; AltName: Full=Stealth protein GNPTAB; AltName: Full=UDP-N-acetylglucosamine-1-phosphotransferase subunits alpha/beta; Contains: RecName: Full=N-acetylglucosamine-1-phosphotransferase subunit alpha; Contains: RecName: Full=N-acetylglucosamine-1-phosphotransferase subunit beta; Flags: Precursor; 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. CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine + lysosomal-enzyme D-mannose = UMP + lysosomal-enzyme N-acetyl-D-glucosaminyl- phospho-D-mannose. SUBUNIT: Hexamer of two alpha, two beta and two gamma subunits; disulfide-linked. It is believed that the alpha and/or the beta subunit of the enzyme contain the catalytic portion and that the gamma subunit functions in recognition of the lysosomal enzymes (By similarity). SUBCELLULAR LOCATION: N-acetylglucosamine-1-phosphotransferase subunit alpha: Golgi apparatus membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: 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. PTM: The alpha- and beta-subunits appear to be generated by a proteolytic cleavage at the Lys-928-Asp-929 bond. DISEASE: Defects in GNPTAB are the cause of mucolipidosis type II (MLII) [MIM:252500]; also known as inclusion cell disease or I- cell disease (ICD). MLII is a 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. DISEASE: Defects in GNPTAB are the cause of mucolipidosis type III complementation group A (MLIIIA) [MIM:252600]; also known as variant pseudo-Hurler polydystrophy. MLIIIA is an 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. 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. MISCELLANEOUS: 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. SIMILARITY: Belongs to the stealth family. SIMILARITY: Contains 1 EF-hand domain. SIMILARITY: Contains 2 LNR (Lin/Notch) repeats. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GNPTAB";