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9  structures 112  species 1  interaction 584  sequences 17  architectures

Family: IMD (PF08397)

Summary: IRSp53/MIM homology domain

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This is the Wikipedia entry entitled "IMD domain". More...

IMD domain Edit Wikipedia article

IRSp53/MIM homology domain
PDB 1wdz EBI.jpg
crystal structure of rcb domain of irsp53
Identifiers
Symbol IMD
Pfam PF08397
Pfam clan CL0145
InterPro IPR013606

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.[1][2][3] The IRSp53/MIM family is a novel F-actin bundling protein family that includes invertebrate relatives:

  • 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).

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.[1][5]

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.[3] The WH2 domain performs a scaffolding function.[6]


References[edit]

  1. ^ a b Yamagishi A, Masuda M, Ohki T, Onishi H, Mochizuki N (April 2004). "A novel actin bundling/filopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein". J. Biol. Chem. 279 (15): 14929–36. doi:10.1074/jbc.M309408200. PMID 14752106. 
  2. ^ Millard TH, Dawson J, Machesky LM (May 2007). "Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties". J. Cell. Sci. 120 (Pt 9): 1663–72. doi:10.1242/jcs.001776. PMID 17430976. 
  3. ^ a b Millard TH, Bompard G, Heung MY, Dafforn TR, Scott DJ, Machesky LM, Fütterer K (January 2005). "Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53". EMBO J. 24 (2): 240–50. doi:10.1038/sj.emboj.7600535. PMC 545821. PMID 15635447. 
  4. ^ Koh JT, Kook H, Kee HJ, Seo YW, Jeong BC, Lee JH, Kim MY, Yoon KC, Jung S, Kim KK (March 2004). "Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin". Exp. Cell Res. 294 (1): 172–84. doi:10.1016/j.yexcr.2003.11.008. PMID 14980512. 
  5. ^ Machesky LM, Johnston SA (June 2007). "MIM: a multifunctional scaffold protein". J. Mol. Med. 85 (6): 569–76. doi:10.1007/s00109-007-0207-0. PMID 17497115. 
  6. ^ Lee SH, Kerff F, Chereau D, Ferron F, Klug A, Dominguez R (February 2007). "Structural basis for the actin-binding function of missing-in-metastasis". Structure 15 (2): 145–55. doi:10.1016/j.str.2006.12.005. PMC 1853380. PMID 17292833. 

This article incorporates text from the public domain Pfam and InterPro IPR013606

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IRSp53/MIM homology domain Provide feedback

The N-terminal predicted helical stretch of the insulin receptor tyrosine kinase substrate p53 (IRSp53) is an evolutionary conserved F-actin bundling domain involved in filopodium formation. The domain has been named IMD after the IRSp53 and missing in metastasis (MIM) proteins in which it occurs. Filopodium-inducing IMD activity is regulated by Cdc42 and Rac1 and is SH3-independent [1].

Literature references

  1. Yamagishi A, Masuda M, Ohki T, Onishi H, Mochizuki N; , J Biol Chem 2004;279:14929-14936.: A novel actin bundling/filopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein. PUBMED:14752106 EPMC:14752106


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013606

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 [PUBMED:14752106, PUBMED:17430976, PUBMED: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 [PUBMED: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 [PUBMED:14752106, PUBMED: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 [PUBMED:15635447]. The WH2 domain performs a scaffolding function [PUBMED:17292833].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Golgi-transport (CL0145), which contains the following 9 members:

Arfaptin BAR BAR_2 BAR_3_WASP_bdg FAM92 IMD Pil1 Sec34 Vps5

Alignments

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(8)
Full
(584)
Representative proteomes NCBI
(490)
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(68)
RP35
(101)
RP55
(199)
RP75
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  Seed
(8)
Full
(584)
Representative proteomes NCBI
(490)
Meta
(0)
RP15
(68)
RP35
(101)
RP55
(199)
RP75
(305)
Alignment:
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  Seed
(8)
Full
(584)
Representative proteomes NCBI
(490)
Meta
(0)
RP15
(68)
RP35
(101)
RP55
(199)
RP75
(305)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Pfam alignments:

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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_4120 (release 18.0)
Previous IDs: none
Type: Family
Author: Wuster A
Number in seed: 8
Number in full: 584
Average length of the domain: 190.70 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 31.80 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 20.5
Trusted cut-off 20.6 20.7
Noise cut-off 20.4 20.4
Model length: 219
Family (HMM) version: 6
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Species distribution

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Interactions

There is 1 interaction for this family. More...

IMD

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IMD domain has been found. There are 9 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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