Cation-dependent mannose-6-phosphate receptor

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This article is about the cation-dependent mannose 6-phosphate receptor. For the cation-independent mannose 6-phosphate receptor, see Insulin-like growth factor 2 receptor.
Mannose-6-phosphate receptor (cation dependent)
PDB 1keo EBI.jpg
PDB rendering based on 1keo.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols M6PR ; CD-MPR; MPR 46; MPR-46; MPR46; SMPR
External IDs OMIM154540 MGI96904 HomoloGene31086 ChEMBL: 5788 GeneCards: M6PR Gene
Species Human Mouse
Entrez 4074 17113
Ensembl ENSG00000003056 ENSMUSG00000007458
UniProt P20645 P24668
RefSeq (mRNA) NM_001207024 NM_010749
RefSeq (protein) NP_001193953 NP_034879
Location (UCSC) Chr 12:
9.09 – 9.1 Mb
Chr 6:
122.31 – 122.32 Mb
PubMed search [1] [2]

In the fields of biochemistry and cell biology, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a protein that in humans is encoded by the M6PR gene.[1][2]

The CD-MPR is one of two transmembrane proteins that bind mannose-6-phosphate (M6P) tags on acid hydrolase precursors in the Golgi apparatus that are destined for transport to the lysosome. Homologues of CD-MPR are found in all eukaryotes.


The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the cytoplasmic side of lipid membranes) with a relatively short cytoplasmic tail.[3] The extracytoplasmic/lumenal M6P binding-domain consists of 157 amino acid residues. The CD-MPR is approximately 46 kDa in size and it both exists and functions as a dimer.

The cell surface receptor for insulin-like growth factor 2 also functions as a cation-independent mannose 6-phosphate receptor.[3] It consists of fifteen repeats homologous to the 157-residue CD-M6PR domain, two of which are responsible for binding to M6P.


Both CD-MPRs and CI-MPRs are lectins that bind their M6P-tagged cargo in the lumen of the Golgi apparatus. The CD-MPR shows greatly enhanced binding to M6P in the presence of divalent cations, such as manganese.[3] The MPRs (bound to their cargo) are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles.[4] They are trafficked to the early endosome where, in the relatively low pH environment of the endosome, the MPRs release their cargo. The MPRs are recycled back to the Golgi, again by way of interaction with GGAs and vesicles. The cargo proteins are then trafficked to the lysosome via the late endosome independently of the MPRs.

See also[edit]


  1. ^ Dahms NM, Lobel P, Breitmeyer J, Chirgwin JM, Kornfeld S (July 1987). "46 kd mannose 6-phosphate receptor: cloning, expression, and homology to the 215 kd mannose 6-phosphate receptor". Cell 50 (2): 181–92. doi:10.1016/0092-8674(87)90214-5. PMID 2954652. 
  2. ^ Pohlmann R, Nagel G, Schmidt B, Stein M, Lorkowski G, Krentler C, Cully J, Meyer HE, Grzeschik KH, Mersmann G (August 1987). "Cloning of a cDNA encoding the human cation-dependent mannose 6-phosphate-specific receptor". Proc. Natl. Acad. Sci. U.S.A. 84 (16): 5575–9. doi:10.1073/pnas.84.16.5575. PMC 298905. PMID 2441386. 
  3. ^ a b c Ghosh P, Dahms NM, Kornfeld S (March 2003). "Mannose 6-phosphate receptors: new twists in the tale". Nat. Rev. Mol. Cell Biol. 4 (3): 202–12. doi:10.1038/nrm1050. PMID 12612639. 
  4. ^ Ghosh P, Kornfeld S (July 2004). "The GGA proteins: key players in protein sorting at the trans-Golgi network". Eur. J. Cell Biol. 83 (6): 257–62. doi:10.1078/0171-9335-00374. PMID 15511083. 

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