Cation-dependent mannose-6-phosphate receptor (IPR000296)

Short name: Man-6-P_rcpt_cation_dep

Overlapping homologous superfamilies

Family relationships


The cation dependent mannose-6-phosphate (man-6-P) receptor is one of two transmembrane proteins involved in the transport of lysosomal enzymes from the Golgi complex and the cell surface to lysosomes [PMID: 1376319]. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to man-6-P receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment, where the low pH mediates dissociation of the complex. Binding is optimal in the presence of divalent cations.

The amino acid sequence is a single polypeptide chain that contains a putative signal sequence and a transmembrane domain [PMID: 2954652]. The cation-dependent mannose 6-phosphate (M6P) receptor (CD-MPR) is present predominantly as a stable homodimer in membranes and has a single M6P-binding site per polypeptide [PMID: 2954652, PMID: 2544594]. The molecule crystallizes as a homodimer with approximately 20% of the entire surface area of each monomer having contact with another through predominantly hydrophobic interactions [PMID: 12612639]. Each monomer contains a single alpha-helix near its amino terminus followed by nine primarily anti-parallel beta-strands that form two beta-sheets, which are positioned orthogonally to each other. Extensive hydrophobic interactions are formed between the two beta-sheets, which results in each monomer forming a flattened beta-barrel structure. Six cysteine residues form three intramolecular disulphide bonds that are essential for the ligand-binding conformation of the receptor to be generated. The structures of the liganded molecules show that the carbohydrate-recognition domain of the enzyme lies relatively deep inside the protein, so that the terminal M6P residue and the penultimate sugar ring of bound pentamannosyl phosphate are mostly buried in the receptor. This deep binding pocket facilitates the formation of numerous interactions between the CD-MPR and its carbohydrate ligands.

GO terms

Biological Process

GO:0015761 mannose transmembrane transport

Molecular Function

GO:0005537 mannose binding
GO:0015578 mannose transmembrane transporter activity

Cellular Component

GO:0016021 integral component of membrane
GO:0000323 lytic vacuole

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.