Mannose-6-phosphate
Encyclopedia
Mannose-6-phosphate is a molecule bound by lectin
in the immune system
. M6P is converted to fructose 6-phosphate
by mannose phosphate isomerase
.
M6P is a targeting signal for acid hydrolase
precursor proteins
that are destined for transport to lysosome
s. The M6P tag is added to such proteins in the cis-Golgi apparatus
. Specifically, in a reaction involving uridine diphosphate
(UDP) and N-acetylglucosamine
, the enzyme UDP-N-acetylglucosamine:N-acetylglucosaminyl-1-phosphotransferase catalyzes the N-linked glycosylation
of asparagine
residues with M6P. Once appropriately marked with the M6P targeting signal, these proteins are moved to the trans-Golgi. There, the M6P moiety is recognized by mannose 6-phosphate receptor
(MPR) proteins.
M6P is also a key marker in ensuring that lysosomal proteins get to the correct organelle within the cell. It attaches to hydrolases. M6P is present on the lysosomal hydrolase at an approximate pH of 6.6 but is released once the pH reaches 6.
The MPRs traffic in vesicles
to the lysosome via an endosome
.
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...
in the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. M6P is converted to fructose 6-phosphate
Fructose 6-phosphate
Fructose 6-phosphate is fructose sugar phosphorylated on carbon 6 . The β-D-form of this compound is very common in cells. The vast majority of glucose and fructose entering a cell will become converted to this at some point...
by mannose phosphate isomerase
Mannose phosphate isomerase
Mannose-6 phosphate isomerase , alternately phosphomannose isomerase is an enzyme which facilitates the interconversion of fructose 6-phosphate and mannose-6-phosphate. Mannose-6-Phosphate Isomerase may also enable the synthesis of GDP-mannose in eukaryotic organisms...
.
M6P is a targeting signal for acid hydrolase
Acid hydrolase
An acid hydrolase is an enzyme that works best at acidic pHs. It is commonly located in lysosomes, which are acidic on the inside. Acid hydrolases may be nucleases, proteases, glycosidases, lipases, phosphatases, sulfatases and phospholipases and make up the approximately 50 degradative enzymes of...
precursor proteins
Protein precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein that can be turned into an active form by posttranslational modification. The name of the precursor for a protein is often prefixed by pro...
that are destined for transport to lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
s. The M6P tag is added to such proteins in the cis-Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
. Specifically, in a reaction involving uridine diphosphate
Uridine diphosphate
Uridine diphosphate, abbreviated UDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside uridine. UDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase uracil.-See also:* Nucleoside...
(UDP) and N-acetylglucosamine
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...
, the enzyme UDP-N-acetylglucosamine:N-acetylglucosaminyl-1-phosphotransferase catalyzes the N-linked glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
of asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
residues with M6P. Once appropriately marked with the M6P targeting signal, these proteins are moved to the trans-Golgi. There, the M6P moiety is recognized by mannose 6-phosphate receptor
Mannose 6-phosphate receptor
In the fields of biochemistry and cell biology, mannose 6-phosphate receptors are proteins that bind newly synthesized lysosomal hydrolases in the trans-Golgi network and deliver them to pre-lysosomal compartments. There are two different MPRs, one of ~300kDa and a smaller, dimeric receptor of...
(MPR) proteins.
M6P is also a key marker in ensuring that lysosomal proteins get to the correct organelle within the cell. It attaches to hydrolases. M6P is present on the lysosomal hydrolase at an approximate pH of 6.6 but is released once the pH reaches 6.
The MPRs traffic in vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
to the lysosome via an endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
.
See also
- insulin-like growth factor 2 receptorInsulin-like growth factor 2 receptorIn the fields of biochemistry and cell biology, the insulin-like growth factor 2 receptor , also called the cation-independent mannose-6-phosphate receptor is a protein that in humans is encoded by the IGF2R gene...
- mannoseMannoseMannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
- I-cell diseaseI-cell diseaseInclusion-cell disease, also referred to as mucolipidosis II , is part of the lysosomal storage disease family and results from a defective phosphotransferase . This enzyme transfers phosphate to mannose residues on specific proteins, and serves as a marker for them to be targeted to lysosomes...
- Mannose 1-phosphateMannose 1-phosphateMannose 1-phosphate is a molecule involved in glycosylation....