GNPTAB

(redirected from GlcNAc phosphotransferase)

GNPTAB

A gene on chromosome 12q23.2 that encodes two of three subunit types of the membrane-bound enzyme N-acetylglucosamine-1-phosphotransferase, a heterohexameric complex composed of 2 alpha, 2 beta and 2 gamma subunits. The encoded protein is proteolytically cleaved to yield mature alpha and beta polypeptides (the gamma subunits are the product of GNPTG). In the Golgi apparatus, the complex catalyses the first step in the synthesis of mannose 6-phosphate recognition markers on oligosaccharides of lysosomal enzyme, which are essential for lysosomal enzyme-targeted trafficking. 

Molecular pathology
GNPTAB mutations are linked to mucolipidosis II (I cell disease) and mucolipidosis IIIA (pseudoHurler polydystrophy).
References in periodicals archive ?
Mucolipidosis (ML) types II and III are caused by a deficiency of GlcNAc phosphotransferase (GNPT), which creates the mannose-6-phosphate lysosomal targeting signal, and is associated with multiple lysosomal hydrolase deficiencies.
[3] Nonstandard abbreviations: LSD, lysosomal storage disease; FOS, free oligosaccharides; MS, mass spectrometry; AGU, aspartylglucosaminuria; ANTS, 2-aminonaphthalene trisulfone; GlcNAc, N-acetylglucosamine; MALDI-TOF/TOF, MALDI-time-of-flight/time-of-flight; DHB, 2,5-dihydroxybenzoic acid; TFA, trifluoroacetic acid; Asn, asparagine; ML, mucolipidosis; GNPT, GlcNAc phosphotransferase.
The phosphorylation of mannose residues is a two-step procedure involving two separate enzymes in the cis Golgi: GlcNAc phosphotransferase and GlcNAc1 phosphodiester N-acetylglucosaminidase.
The lack of the first enzyme, GlcNAc phosphotransferase, causes 1-cell disease, a lysosomal storage disease, which leads to a deficiency of multiple enzymes in fibroblasts and macrophages.