9.B.247. The Mannose 6-Phosphate Receptor (M6PR) Family 

The two members of the P-type lectin family, the 46 kDa cation-dependent mannose 6-phosphate receptor (CD-MPR) and the 300 kDa cation-independent mannose 6-phosphate receptor (CI-MPR), are ubiquitously expressed throughout the animal kingdom and are distinguished from all other lectins by their ability to recognize phosphorylated mannose residues (Dahms et al. 2008). The best-characterized function of the MPRs is their ability to direct the delivery of approximately 60 different newly synthesized soluble lysosomal enzymes bearing mannose 6-phosphate (Man-6-P) on their N-linked oligosaccharides to the lysosome. In addition to its intracellular role in lysosome biogenesis, the CI-MPR, but not the CD-MPR, participates in a number of other biological processes by interacting with various molecules at the cell surface. The list of extracellular ligands recognized by this multifunctional receptor has grown to include a diverse spectrum of Man-6-P-containing proteins as well as several non-Man-6-P-containing ligands. Structural studies have provided a clearer view of how these two receptors use related, but yet distinct, approaches in the recognition of phosphomannosyl residues (Dahms et al. 2008).

The cation-dependent mannose 6-phosphate receptor (CD-MPR) is a single-pass type I membrane protein that functions to transport lysosomal enzymes displaying phosphomannosyl residues from the Golgi complex and the cell surface to the lysosome. This glycosylated protein contains three disulfide bridges in its 159-residue extracytoplasmic domain (Olson and Dahms 2018).



Dahms, N.M., L.J. Olson, and J.J. Kim. (2008). Strategies for carbohydrate recognition by the mannose 6-phosphate receptors. Glycobiology 18: 664-678.

Ikushima, H., Y. Munakata, T. Ishii, S. Iwata, M. Terashima, H. Tanaka, S.F. Schlossman, and C. Morimoto. (2000). Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc. Natl. Acad. Sci. USA 97: 8439-8444.

Olson, L.J. and N.M. Dahms. (2018). Cloning, Expression, and Purification of the Glycosylated Transmembrane Protein, Cation-Dependent Mannose 6-Phosphate Receptor, from Sf9 Cells Using the Baculovirus System. Methods Mol Biol 1722: 105-116.


TC#NameOrganismal TypeExample

The cation-dependent mannose-6-phosphate receptor isoform 1 precursorof 277 aas and 1 TMS, M6PR, MPR46, MPRD.

M6PR of Homo sapiens


The cation-independent mannose 6-phosphate receptor precursor, MPR or IGF2R, of 2491 aas and 2 TMSs.  MPR transports phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH causes dissociation of the complex. This receptor also binds IGF2. It acts as a positive regulator of T-cell coactivation by binding DPP4 (Ikushima et al. 2000).

MPR of Homo sapiens


Cation-dependent mannose-6-phosphate receptor, M6PR, of 300 aas and 1 probable TMS.

M6PR of Trachymyrmex septentrionalis


Uncharacterized protein of 291 aas and 1 probable TMS.

UP of Fusarium oxysporum (Fusarium vascular wilt)


Autophgy-like protein of 195 aas and 1 TMS.

Autophagy-like protein of Arabidopsis thaliana (Mouse-ear cress)


Cation-independent mannose-6-phosphate receptor-like protein of 2389 aas and 2 TMSs, MPR.

MPR of Sinocyclocheilus rhinocerous


Uncharacterized protein of 255 aas and 1 TMS.

UP of Dictyostelium discoideum (Slime mold)


Uncharacterized protein of 965 aas and 2 - 3 TMSs.  The first 360 aas resemble kinesin-1 (TC# 1.P.1.1.1) while the last 100 residues resemble the last 100 residues in other members of family 9.B.247 (The Mannose 6-P Receptor) Family, including the C-terminal 2 TMSs.

kinesin homologue of Paramecium tetraurelia


Uncharacterized protein of 275 aas and 2 - 3 TMSs.

UP of Trypanosoma cruzi