title: Mannose 6-phosphate receptor homology (MRH) domain-containing lectins in the secretory pathway.
abstract: BACKGROUND
  The mannose 6-phosphate receptor homology (MRH) domain-containing family of proteins, which include recycling receptors (mannose 6-phosphate receptors, MPRs), resident endoplasmic reticulum (ER) proteins (glucosidase II β-subunit, XTP3-B, OS-9), and a Golgi glycosyltransferase (GlcNAc-phosphotransferase γ-subunit), are characterized by the presence of one or more MRH domains. Many MRH domains act as lectins and bind specific phosphorylated (MPRs) or non-phosphorylated (glucosidase II β-subunit, XTP3-B and OS-9) high mannose-type N-glycans. The MPRs are the only proteins known to bind mannose 6-phosphate (Man-6-P) residues via their MRH domains.
  
  
  METHODS
  Recent biochemical and structural studies that have provided valuable insight into the glycan specificity and mechanisms of carbohydrate recognition by this diverse group of MRH domain-containing proteins are highlighted.
  
  
  CONCLUSIONS
  Currently, three-dimensional structures are known for ten MRH domains, revealing the conservation of a similar fold. OS-9 and the MPRs use the same four residues (Gln, Arg, Glu, and Tyr) to bind mannose.
  
  
  CONCLUSIONS
  The MRH domain-containing proteins play key roles in the secretory pathway: glucosidase II, XTP3-B, and OS-9 are involved in the recognition of nascent glycoproteins, whereas the MPRs play an essential role in lysosome biogenesis by targeting Man-6-P-containing lysosomal enzymes to the lysosome.
authors: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors: Alicia C
authors: AC
authors: Castonguay
authors: Linda J
authors: LJ
authors: Olson
authors: Nancy M
authors: NM
authors: Dahms
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000502:physiology; D008360:Mannosephosphates / Q000378:metabolism; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry; D011134:Polysaccharides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000378:metabolism; D055571:Secretory Pathway / Q000502:physiology*; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D037102:Lectins; D008360:Mannosephosphates; D009363:Neoplasm Proteins; C098898:OS9 protein, human; D011134:Polysaccharides; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate