N-acetylglucosamine-1-phosphate transferase is a
transferase
A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds o ...
enzyme.
Function
It is made up of two alpha (α), two betas (β), and two gammas (γ) subunits. ''GNPTAB'' produces the alpha and beta subunits, ''
GNPTG'' produces the gamma subunit. GlcNAc-1-phosphotransferase functions to prepare newly made enzymes for lysosome transportation (lysosomal hydrolases to the lysosome).
Lysosome
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane p ...
s, a part of an animal cell, helps break down large molecules into smaller ones that can be reused. GlcNAc-1-phosphotransferase catalyzes the N-linked
glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...
of asparagine residues with a molecule called
mannose-6-phosphate
Mannose-6-phosphate (M6P) is a molecule bound by lectin in the immune system. M6P is converted to fructose 6-phosphate by mannose phosphate isomerase.
M6P is a key targeting signal for acid hydrolase precursor proteins that are destined for tran ...
(M6P). M6P acts as an indicator of whether a hydrolase should be transported to the lysosome or not. Once a hydrolase indicates an M6P, it can be transported to a lysosome. Surprisingly some lysosomal enzymes are only tagged at a rate of 5% or lower.
Clinical significance
It is associated with the following conditions:
* mucolipidosis II alpha/beta (
I-cell disease
Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II (ML II), is part of the lysosomal storage disease family and results from a defective phosphotransferase (an enzyme of the Golgi apparatus). This enzyme transfers phosphate to ...
) - GNPTAB
* mucolipidosis III alpha/beta (
pseudo-Hurler polydystrophy) - GNPTAB
* mucolipidosis III gamma - GNPTG
* stuttering (Kang et al., 2010)
In melanocytic cells, GNPTG gene expression may be regulated by
MITF
Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene.
MITF is a basic helix-loop-helix leucine zipper transcription fact ...
.
References
Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J.C., and Drayna, D. (2010). Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering. New England Journal of Medicine 362, 677–685.
External links
GeneReviews/NCBI/NIH/UW entry on Mucolipidosis III Alpha/Beta GeneReviews/NIH/NCBI/UW entry on Mucolipidosis II GeneReviews/NIH/NCBI/UW entry on Mucolipidosis III Gamma
*
*
{{enzyme-stub