Domain

IRSp53/MIM homology domain (IMD) (IPR013606)

Short name: IRSp53/MIM_homology_IMD

Domain relationships

None.

Description

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 [PMID: 14752106, PMID: 17430976, PMID: 15635447]. The IRSp53/MIM family is a novel F-actin bundling protein family that includes invertebrate relatives:

  • Vertebrate MIM (missing in metastasis), 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 [PMID: 14980512].
  • 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 (Fruit fly) 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 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 [PMID: 14752106, PMID: 17497115].

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 [PMID: 15635447]. The WH2 domain performs a scaffolding function [PMID: 17292833].

GO terms

Biological Process

GO:0046847 filopodium assembly
GO:0007165 signal transduction

Molecular Function

GO:0017124 SH3 domain binding
GO:0008093 cytoskeletal adaptor activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam
PROSITE profiles