PROSITE documentation PDOC51338IMD 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 α-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.
Last update:November 2007 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Yamagishi A. Masuda M. Ohki T. Onishi H. Mochizuki N. |
| Title | A novel actin bundling/filopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein. | |
| Source | J. Biol. Chem. 279:14929-14936(2004). | |
| PubMed ID | 14752106 | |
| DOI | 10.1074/jbc.M309408200 |
| 2 | Authors | Machesky L.M. Johnston S.A. |
| Title | MIM: a multifunctional scaffold protein. | |
| Source | J. Mol. Med. 85:569-576(2007). | |
| PubMed ID | 17497115 | |
| DOI | 10.1007/s00109-007-0207-0 |
| 3 | Authors | Millard T.H. Bompard G. Heung M.Y. Dafforn T.R. Scott D.J. Machesky L.M. Fuetterer K. |
| Title | Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53. | |
| Source | EMBO J. 24:240-250(2005). | |
| PubMed ID | 15635447 | |
| DOI | 10.1038/sj.emboj.7600535 |
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