IRSp53/MIM homology domain (IMD)
InterPro Protein Domain record
-
description
-
-
<p>The IMD (IRSp53 and MIM (missing in metastases) homology) domain is a BAR-like domain of approximately 250 amino acids found at the N-terminal in the insulin receptor tyrosine kinase substrate p53 (IRSp53) and in the evolutionarily related IRSp53/MIM family. In IRSp53, a ubiquitous regulator o the actin cytoskeleton, the IMD domain acts as conserved F-actin bundling domain involved in filopodium formation. Filopodium-inducing IMD activity is regulated by Cdc42 and Rac1 (Rho-family GTPases) and is SH3-independent [<cite idref="PUB00020898"/>, <cite idref="PUB00035722"/>, <cite idref="PUB00032568"/>]. The IRSp53/MIM family is a novel F-actin bundling protein family that includes invertebrate relatives:</p><p> <ul> <li> Vertebrate MIM (missing in metastasis), an actin-binding scaffold protein that may be involved in cancer metastasis.</li><li> Vertebrate ABBA-1, a MIM-related protein.</li><li>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 [<cite idref="PUB00035723"/>].</li><li> Vertebrate brain-specific angiogenesis inhibitor 1-associated protein 2-like proteins 1 and 2 (BAI1-associated protein 2-like proteins 1 and 2).</li><li> <taxon tax_id="7227">Drosophila melanogaster</taxon> (Fruit fly) CG32082-PA.</li><li> <taxon tax_id="6239">Caenorhabditis elegans</taxon> M04F3.5 protein.</li> </ul> </p><p>The vertebrate IRSp53/MIM family is divided into two major groups: the IRSp53 subfamily and the MIM/ABBA subfamily. The putative invertebrate homologues are positioned between them. The IRSp53 subfamily members contain an SH3 domain, and the MIM/ABBA subfamily proteins contain a WH2 (WASP-homology 2) domain. 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 [<cite idref="PUB00020898"/>, <cite idref="PUB00043717"/>].</p><p> The IMD domain folds as a coiled coil of three extended alpha-helices and a shorter C-terminal helix. 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, a functional module serving both as a sensor and inducer of membrane curvature [<cite idref="PUB00032568"/>]. The WH2 domain performs a scaffolding function [<cite idref="PUB00035721"/>].</p>
-
label
-
-
IRSp53/MIM homology domain (IMD)
-
attributionURL
-
-
signatures_SMART
-
-
type
-
-
seeAlso
-
-
children
-
-
contains
-
-
PDB_structure
-
-
Pfam-A
-