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We are deeply saddened by the passing of Amos Bairoch (1957–2025), the creator of PROSITE. We wish to dedicate our latest paper, published shortly before his death, to him. He will always be a source of inspiration to us.
Our deepest condolences go out to his family and friends, and to all those who had the privilege of working with him. Rest in peace, Amos. Your work will live on long after you are gone.
Amos Bairoch

PROSITE documentation PDOC51914
MRH domain profile


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PURL: https://purl.expasy.org/prosite/documentation/PDOC51914

Description

The mannose 6-phosphate (Man-6-P) receptor homology (MRH) domain-containing family of proteins, which include recycling receptors (mannose 6-phosphate receptors, MRPs), 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 (glycosidase II β-subunit (GIIβ, XTP3-B and OS-9) high mannose-type N-glycans. The MPRs are the only proteins known to bind Man-6-P residues via their MRH domains. The MRH domain can function in protein-carbohydrate and protein-protein interactions [1,2,3,4,5,6,7].

The overall fold of the MRH domain comprises a flattened β-barrel structure consisting of nine β-strands organized into two orthogonally oriented anti-parallel β-sheets, β1-β4 and β5-β9, with β9 interjecting between β7 and β8 (see <PDB:1SZ0>). MRH domains display a similar size and conservation of residues, including cysteines involved in disulfide bonding. The GIIβ MRH domain contains only two disulfide bonds in contrast to the three (OS-9, CD-MPR, CI-MPR domain 5) or four (CI-MPR domains 3 and 9) [3,4].

The profile we developed covers the entire MRH domain.

Last update:

February 2020 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

MRH, PS51914; MRH domain profile  (MATRIX)


References

1AuthorsMunro S.
TitleThe MRH domain suggests a shared ancestry for the mannose 6-phosphate receptors and other N-glycan-recognising proteins.
SourceCurr. Biol. 11:R499-R501(2001).
PubMed ID11470418
DOI10.1016/s0960-9822(01)00302-5

2AuthorsCastonguay A.C. Olson L.J. Dahms N.M.
TitleMannose 6-phosphate receptor homology (MRH) domain-containing lectins in the secretory pathway.
SourceBiochim. Biophys. Acta. 1810:815-826(2011).
PubMed ID21723917
DOI10.1016/j.bbagen.2011.06.016

3AuthorsOlson L.J. Orsi R. Alculumbre S.G. Peterson F.C. Stigliano I.D. Parodi A.J. D'Alessio C. Dahms N.M.
TitleStructure of the lectin mannose 6-phosphate receptor homology (MRH) domain of glucosidase II, an enzyme that regulates glycoprotein folding quality control in the endoplasmic reticulum.
SourceJ. Biol. Chem. 288:16460-16475(2013).
PubMed ID23609449
DOI10.1074/jbc.M113.450239

4AuthorsOlson L.J. Orsi R. Peterson F.C. Parodi A.J. Kim J.J. D'Alessio C. Dahms N.M.
TitleCrystal Structure and Functional Analyses of the Lectin Domain of Glucosidase II: Insights into Oligomannose Recognition.
SourceBiochemistry 54:4097-4111(2015).
PubMed ID26062005
DOI10.1021/acs.biochem.5b00256

5AuthorsD'Alessio C. Dahms N.M.
TitleGlucosidase II and MRH-domain containing proteins in the secretory pathway.
SourceCurr. Protein. Pept. Sci. 16:31-48(2015).
PubMed ID25692846
DOI10.2174/1389203716666150213160438

6AuthorsSzathmary R. Bielmann R. Nita-Lazar M. Burda P. Jakob C.A.
TitleYos9 protein is essential for degradation of misfolded glycoproteins and may function as lectin in ERAD.
SourceMol. Cell. 19:765-775(2005).
PubMed ID16168372
DOI10.1016/j.molcel.2005.08.015



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