EC Number   |
General Information |
Reference |
|---|
   2.7.8.17 | malfunction |
30% of the acid hydrolases of gamma gene knockout mice brain are phosphorylated at levels equivalent to that in wild-type brain, although 25% are poorly phosphorylated compared to wild-type. The rest of the acid hydrolases of the gamma-deficient sample are phosphorylated at an intermediate level. This shows that some acid hydrolases are highly dependent on the presence of the gamma subunit to acquire the Man-6-P, although others are well phosphorylated by the alpha/beta subunits alone |
725407 |
| 2.7.8.17 | malfunction |
deletion of the Alg14 N-terminal region causes a severe growth defect at high temperature. Malfunction can be partially complemented by overexpression of Alg7 |
722362 |
| 2.7.8.17 | malfunction |
extracts of two mutant cell lines transfer UDP-N-acetyl-D-glucosamine from N-acetyl-D-glucosamine to mannose residues at less than 5% the wild type value. In addition, the lysosomal hydrolases of these mutant clones fail to bind to a cation-independent mannose 6-phosphate receptor affinity column |
724169 |
| 2.7.8.17 | malfunction |
loss of function results in impaired lysosomal targeting of these acid hydrolases and decreased lysosomal degradation. Two mucolipidosis III patient missense mutations, Lys4Gln and Ser15Tyr, in the N-terminal cytoplasmic tail of the alpha-subunit of phosphotransferase impair retention of the catalytically active enzyme in the Golgi complex. This results in mistargeting of the mutant enzymes to lysosomes, where they are degraded, or to the cell surface and release into the medium. The mislocalization of the active enzymes is the basis for mucolipidosis III alphabeta in a subset of patients |
739540 |
| 2.7.8.17 | malfunction |
mucolipidoses II and III (ML II and MLIII) are lysosomal disorders in which the mannose 6-phosphate recognition marker is absent from lysosomal hydrolases and other glycoproteins due to mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Both disorders are caused by the same gene, but ML II represents the more severe phenotype. Bone manifestations of ML II include hip dysplasia, scoliosis, rickets and osteogenesis imperfecta, phhentype overview. A recombinant adeno-associated viral vector (AAV2/8-GNPTAB) confers high and prolonged gene expression of GNPTAB and thereby influence the pathology in the cartilage and bone tissue of a GNPTAB knock out (KO) mouse model. AAV8-mediated expression of N-acetylglucosamine-1-phosphate transferase attenuates bone loss in a mouse model of mucolipidosis II with significant increases in bone mineral density and content |
739081 |
| 2.7.8.17 | malfunction |
mucolipidosis II (MLII) and III alpha/beta are autosomal-recessive diseases of childhood caused by mutations in GNPTAB encoding the alpha/beta-subunit precursor protein of the GlcNAc-1-phosphotransferase complex. Biological significance of eight selected disease-causing GNPTAB mutations found in MLII and MLIII alpha/beta patients in Brazil, overview. The frameshift E757KfsX1 and the non-sense R587X mutations result in a severe clinical phenotype in homozygosity. In addition to the loss of combinatorial cytosolic targeting motifs, luminal missense mutations located in the stealth region 2 of the alpha-subunit impair the transport of the alpha/beta-subunit precursor to the Golgi apparatus |
738351 |
| 2.7.8.17 | malfunction |
recombinant GlcNAc-1-phosphotransferase containing a missense mutation in the DMAP interaction domain (Lys732Asn) identified in a patient with mucolipidosis II exhibits full activity toward the simple sugar alpha-methyl D-mannoside but impaired phosphorylation activity toward acid hydrolases, recombinant expression of the K732N mutant in a zebrafish model of mucolipidosis II fails to correct the phenotypic abnormalities |
739527 |
| 2.7.8.17 | malfunction |
some mutations in the Stealth domain harboring the catalytic site greatly impaires the activity of the enzyme without affecting its Golgi localization and proteolytic processing. Missense mutations in conserved cysteine residues in the Notch repeat 1 domain do not affect the catalytic activity but impair mannose phosphorylation of certain lysosomal hydrolases |
738667 |
| 2.7.8.17 | malfunction |
the lysosomal storage disorder ML III gamma is caused by defects in the gamma subunit of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. In patients with this disorder, most of the newly synthesized lysosomal enzymes are secreted rather than being sorted to lysosomes, resulting in increased levels of these enzymes in the plasma. Several missense mutations in GNPTG, the gene encoding the gamma subunit, are reported in mucolipidosis III gamma patients. gamma-Subunit deficient HeLa cells have greatly reduced levels of many lysosomal acid hydrolases compared with the parental HeLa cells and display a lysosomal storage phenotype |
738354 |
| 2.7.8.17 | more |
identification of domains of the enzyme involved in catalytic function, overview |
738667 |
