{PDOC51338}
{PS51338; IMD}
{BEGIN}
**********************
* IMD domain profile *
**********************

The N-terminal  IRSp53  and  MIM homology domain (IMD) is a BAR-like domain of
~250 amino  acids  that  is  conserved  in  an  evolutionarily related protein
family, the  IRSp53/MIM  family.  The  IRSp53/MIM  family  is  a novel F-actin
bundling protein family that includes invertebrate relatives:

 - Vertebrate  missing  in metastasis (MIM), an actin-binding scaffold protein
   that may be involved in cancer metastasis.
 - Vertebrate ABBA-1, a MIM-related protein.
 - Vertebrate  brain-specific  angiogenesis  inhibitor  1-associated protein 2
   (BAI1-associated protein  2)  or insulin receptor tyrosine kinase substrate
   p53 (IRSp53),  a  multifunctional  adaptor  protein  that links Rac1 with a
   Wiskott-Aldrich syndrome  family  verprolin-homologous protein 2 (WAVE2) to
   induce lamellipodia or Cdc42 with Mena to induce filopodia.
 - Vertebrate  brain-specific  angiogenesis  inhibitor 1-associated protein 2-
   like proteins 1 and 2 (BAI1-associated protein 2-like proteins 1 and 2).
 - Drosophila melanogaster CG32082-PA.
 - Caenorhabditis elegans M04F3.5 protein.

The vertebrate  IRSp53/MIM family is divided into two major groups: the IRSp53
subfamily and  the  MIM/ABBA subfamily. The putative invertebrate homologs are
positioned between  them.  The  IRSp53 subfamily members contain an SH3 domain
(see <PDOC50002>),  and  the  MIM/ABBA subfamily proteins contain a WH2 domain
(see <PDOC51082>).  The vertebrate SH3-containing subfamily is further divided
into three  groups  according  to  the  presence or absence of the WWB and the
half-CRIB motif.  The  IMD domain can bind to and bundle actin filaments, bind
to membranes and interact with the small GTPase Rac [1,2].

The IMD  domain  folds  as a coiled coil of three extended alpha-helices and a
shorter C-terminal  helix  (see <PDB:1Y2O>). Helix 4 packs tightly against the
other three  helices,  and thus represents an integral part of the domain. The
fold of the IMD domain closely resembles that of the BAR (Bin-Amphiphysin-RVS)
domain (see  <PDOC51021>),  a  functional  module serving both as a sensor and
inducer of membrane curvature [3].

The profile we developed covers the entire IMD domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 2007 / First entry.

[ 1] Yamagishi A., Masuda M., Ohki T., Onishi H., Mochizuki N.
     "A novel actin bundling/filopodium-forming domain conserved in insulin
     receptor tyrosine kinase substrate p53 and missing in metastasis
     protein."
     J. Biol. Chem. 279:14929-14936(2004).
     PubMed=14752106; DOI=10.1074/jbc.M309408200
[ 2] Machesky L.M., Johnston S.A.
     "MIM: a multifunctional scaffold protein."
     J. Mol. Med. 85:569-576(2007).
     PubMed=17497115; DOI=10.1007/s00109-007-0207-0
[ 3] Millard T.H., Bompard G., Heung M.Y., Dafforn T.R., Scott D.J.,
     Machesky L.M., Fuetterer K.
     "Structural basis of filopodia formation induced by the IRSp53/MIM
     homology domain of human IRSp53."
     EMBO J. 24:240-250(2005).
     PubMed=15635447; DOI=10.1038/sj.emboj.7600535

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}