Mannose 6-phosphate receptor
| Cation-independent mannose-6-phosphate receptor repeat | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | CIMR | ||||||||
| Pfam | PF00878 | ||||||||
| InterPro | IPR000479 | ||||||||
| SCOP | 1e6f | ||||||||
| SUPERFAMILY | 1e6f | ||||||||
|
|||||||||
| Available protein structures: | |
|---|---|
| Pfam | structures |
| PDB | RCSB PDB; PDBe; PDBj |
| PDBsum | structure summary |
| Cation-dependent mannose-6-phosphate receptor | |
|---|---|
| Identifiers | |
| Symbol | M6PR |
| Entrez | 4074 |
| HUGO | 6752 |
| OMIM | 154540 |
| RefSeq | NM_002355 |
| UniProt | P20645 |
| Other data | |
| Locus | Chr. 12 p13 |
| Cation-independent mannose-6 phosphate receptor | |
|---|---|
| Identifiers | |
| Symbol | IGF2R |
| Entrez | 3482 |
| HUGO | 5467 |
| OMIM | 147280 |
| RefSeq | NM_000876 |
| UniProt | P11717 |
| Other data | |
| Locus | Chr. 6 q25q27 |
The mannose 6-phosphate receptors (MPRs) are transmembrane glycoproteins that target enzymes to lysosomes in vertebrates.
Mannose 6-phosphate receptors bind newly synthesized lysosomal hydrolases in the trans-Golgi network (TGN) and deliver them to pre-lysosomal compartments. There are two different MPRs, one of ~300kDa and a smaller, dimeric receptor of ~46kDa. The larger receptor is known as the cation-independent mannose 6-phosphate receptor (CI-MPR), while the smaller receptor (CD-MPR) requires divalent cations to efficiently recognize lysosomal hydrolases. While divalent cations are not essential for ligand binding by the human CD-MPR, the nomenclature has been retained.
Both of these receptors bind terminal mannose 6-phosphate with similar affinity (CI-MPR = 7 μM, CD-MPR = 8 μM) and have similar signals in their cytoplasmic domains for intracellular trafficking.
Elizabeth Neufeld was studying patients who had multiple inclusion bodies present in their cells. Due to the large amount of inclusion bodies she named this condition I-cell disease. These inclusion bodies represented lysosomes that were filled with undigestable material. At first Neufeld thought these patients must have a lack of lysosomal enzymes. . Further study showed that all of the lysosomal enzymes were being made but they were being incorrectly targeted. Instead of being sent to the lysosome, they were being secreted. Furthermore, these mis-targeted enzymes were found to not be phosphorylated. Therefore, Neufeld suggested that I-cell disease was caused by a deficiency in the enzymes that add a specific mannose 6-phosphate tag onto lysosomal enzymes so they can be targeted to the lysosome.
...
Wikipedia