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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.
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Amos Bairoch

PROSITE documentation PDOC51072
Mu homology domain (MHD) profile


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PURL: https://purl.expasy.org/prosite/documentation/PDOC51072

Description

The mu homology domain (MHD) is an ~280 residue protein-protein interaction module, which is found in endocytotic proteins involved in clathrin-mediated endocytosis [1,2,3,4]:

  • Mu subunits of adaptor protein (AP) complexes, AP-1, AP-2, AP-3, and AP-4 (see <PDOC00761>).
  • Proteins of the stonin family.
  • Proteins of the muniscin family: Syp1, FCHO1/2 and SGIP1.

The MHD domain has an elongated, banana-shaped, all β-sheet structure (see <PDB:1BW8>). It can be considered as two β-sandwich subdomains (A and B), with subdomain B inserted between strands 6 and 15 of subdomain A, and joined edge to edge such that the convex surface is a continuous nine-stranded mixed β-sheet that runs the whole length of the molecule. The tyrosine based signal binds to a site on the surface of two parallel β-sheet strands (β1 and β16) in subdomain A [4,5].

The profile we developed covers the entire MHD domain.

Last update:

October 2013 / Text revised.

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Technical section

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

MHD, PS51072; Mu homology domain (MHD) profile  (MATRIX)


References

1AuthorsMartina J.A. Bonangelino C.J. Aguilar R.C. Bonifacino J.S.
TitleStonin 2: an adaptor-like protein that interacts with components of the endocytic machinery.
SourceJ. Cell Biol. 153:1111-1120(2001).
PubMed ID11381094

2AuthorsWalther K. Krauss M. Diril M.K. Lemke S. Ricotta D. Honing S. Kaiser S. Haucke V.
TitleHuman stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating.
SourceEMBO Rep. 2:634-640(2001).
PubMed ID11454741
DOI10.1093/embo-reports/kve134

3AuthorsWalther K. Diril M.K. Jung N. Haucke V.
TitleFunctional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin.
SourceProc. Natl. Acad. Sci. U.S.A. 101:964-969(2004).
PubMed ID14726597
DOI10.1073/pnas.0307862100

4AuthorsReider A. Barker S.L. Mishra S.K. Im Y.J. Maldonado-Baez L. Hurley J.H. Traub L.M. Wendland B.
TitleSyp1 is a conserved endocytic adaptor that contains domains involved in cargo selection and membrane tubulation.
SourceEMBO J. 28:3103-3116(2009).
PubMed ID19713939
DOI10.1038/emboj.2009.248

5AuthorsOwen D.J. Evans P.R.
TitleA structural explanation for the recognition of tyrosine-based endocytotic signals.
SourceScience 282:1327-1332(1998).
PubMed ID9812899



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