Trisha Shetty (Editor)

IMD domain

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Symbol
  
IMD

Pfam clan
  
CL0145

Pfam
  
structures

Pfam
  
PF08397

InterPro
  
IPR013606

PDB
  
RCSB PDB; PDBe; PDBj

IMD domain

In molecular biology, the IMD domain (IRSp53 and MIM (missing in metastases) homology Domain) is a BAR-like domain of approximately 250 amino acids found at the N-terminus in the insulin receptor tyrosine kinase substrate p53 (IRSp53/BAIAP2) and in the evolutionarily related IRSp53/MIM (MTSS1) family. In IRSp53, a ubiquitous regulator of 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. The IRSp53/MIM family is a novel F-actin bundling protein family that includes invertebrate relatives:

  • Vertebrate MIM (missing in metastasis) (MTSS1), an actin-binding scaffold protein that may be involved in cancer metastasis.
  • Vertebrate ABBA-1 (MTSS1L), 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/WASF2) to induce lamellipodia or Cdc42 with Mena to induce filopodia.
  • Vertebrate brain-specific angiogenesis nhibitor 1-associated protein 2-like proteins 1 and 2 (BAI1-associated protein 2-like proteins 1 and 2, BAIAP2L1 and BAIAP2L2).
  • 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.

    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. The WH2 domain performs a scaffolding function.

    References

    IMD domain Wikipedia
    (Text) CC BY-SA