Summary: IRSp53/MIM homology domain
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IMD domain Edit Wikipedia article
|IRSp53/MIM homology domain|
crystal structure of rcb domain of irsp53
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 IMD domain is also known as the I-BAR domain because of its inverse curvature of the membrane binding surface compared to that of the BAR domain. The WH2 domain performs a scaffolding function.
- 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.
- 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.
- 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 . PMID 15635447.
- 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.
- 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.
- 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 . PMID 17292833.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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 .
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
Internal database links
|SCOOP:||BAR BAR_2 BAR_3|
This tab holds annotation information from the InterPro database.
InterPro entry IPR013606
The I-BAR domain (also known as IMD domain, IRSp53 and MIM homology domain) is a BAR-like domain of approximately 250 amino acids found at the N-terminal in the IRSp53 (insulin receptor tyrosine kinase substrate p53) and in the evolutionarily related IRSp53/MIM family. The BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. The BAR domain containing proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature [PUBMED:21743456, PUBMED:21093245]. The I-BAR domain containing proteins include:
- Vertebrate MIM (missing in metastasis), an actin-binding scaffold protein that may be involved in cancer metastasis.
- Vertebrate ABBA, a MIM-related protein.
- Vertebrate 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 IRTKS.
- Vertebrate Pinkbar.
- Drosophila melanogaster (Fruit fly) CG32082-PA.
- Caenorhabditis elegans M04F3.5 protein.
The vertebrate I-BAR family is divided into two major groups: the IRSp53/IRTKS/Pinkbar subfamily and the MIM/ABBA subfamily. The putative invertebrate homologues are positioned between them. The IRSp53/IRTKS/Pinkbar subfamily members contain a 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 [PUBMED:14752106, PUBMED:17497115]. The BAR domain binds phosphoinositide-rich vesicles with high affinity and does not display strong actin filament binding/bundling activity [PUBMED:21093245, PUBMED:17371834].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||plasma membrane organization (GO:0007009)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan contains families that are involved in intracellular transport and signalling. Arfaptins are proteins which interact with small GTPases involved in vesicular budding at the Golgi complex. They form an elongated dimer of three helix coiled coils and are structurally very similar to the BAR domain . The Sec34 family is involved in tethering vesicles to the Golgi .
The clan contains the following 9 members:Arfaptin BAR BAR_2 BAR_3 BAR_3_WASP_bdg FAM92 FCH IMD Vps5
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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|Seed source:||Pfam-B_4120 (release 18.0)|
|Number in seed:||5|
|Number in full:||1027|
|Average length of the domain:||179.60 aa|
|Average identity of full alignment:||29 %|
|Average coverage of the sequence by the domain:||30.62 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||10|
|Download:||download the raw HMM for this family|
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How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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There are 2 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 13 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 sequence.
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