{PDOC51914}
{PS51914; MRH}
{BEGIN}
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* MRH domain profile *
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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
beta-subunit, XTP3-B,   OS-9),   and   a  Golgi  glycosyltransferase  (GlcNAc-
phosphotransferase gamma-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  beta-subunit
(GIIbeta, 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 beta-barrel structure
consisting of nine beta-strands organized into two orthogonally oriented anti-
parallel beta-sheets,  beta1-beta4  and  beta5-beta9,  with beta9 interjecting
between beta7  and  beta8 (see <PDB:1SZ0>). MRH domains display a similar size
and conservation  of  residues,  including  cysteines  involved  in  disulfide
bonding. The  GIIbeta 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2020 / First entry.

[ 1] Munro S.
     "The MRH domain suggests a shared ancestry for the mannose 6-phosphate
     receptors and other N-glycan-recognising proteins."
     Curr. Biol. 11:R499-R501(2001).
     PubMed=11470418; DOI=10.1016/s0960-9822(01)00302-5
[ 2] Castonguay A.C., Olson L.J., Dahms N.M.
     "Mannose 6-phosphate receptor homology (MRH) domain-containing lectins
     in the secretory pathway."
     Biochim. Biophys. Acta. 1810:815-826(2011).
     PubMed=21723917; DOI=10.1016/j.bbagen.2011.06.016
[ 3] Olson L.J., Orsi R., Alculumbre S.G., Peterson F.C., Stigliano I.D.,
     Parodi A.J., D'Alessio C., Dahms N.M.
     "Structure 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."
     J. Biol. Chem. 288:16460-16475(2013).
     PubMed=23609449; DOI=10.1074/jbc.M113.450239
[ 4] Olson L.J., Orsi R., Peterson F.C., Parodi A.J., Kim J.J.,
     D'Alessio C., Dahms N.M.
     "Crystal Structure and Functional Analyses of the Lectin Domain of
     Glucosidase II: Insights into Oligomannose Recognition."
     Biochemistry 54:4097-4111(2015).
     PubMed=26062005; DOI=10.1021/acs.biochem.5b00256
[ 5] D'Alessio C., Dahms N.M.
     "Glucosidase II and MRH-domain containing proteins in the secretory
     pathway."
     Curr. Protein. Pept. Sci. 16:31-48(2015).
     PubMed=25692846; DOI=10.2174/1389203716666150213160438
[ 6] Szathmary R., Bielmann R., Nita-Lazar M., Burda P., Jakob C.A.
     "Yos9 protein is essential for degradation of misfolded glycoproteins
     and may function as lectin in ERAD."
     Mol. Cell. 19:765-775(2005).
     PubMed=16168372; DOI=10.1016/j.molcel.2005.08.015

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