|SMART accession number:||SM00320|
|Description:||Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.|
|Interpro abstract (IPR001680):|
WD-40 repeats (also known as WD or beta-transducin repeats) are short ~40 amino acid motifs, often terminating in a Trp-Asp (W-D) dipeptide. WD40 repeats usually assume a 7-8 bladed beta-propeller fold, but proteins have been found with 4 to 16 repeated units, which also form a circularised beta-propeller structure. WD-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control and apoptosis. Repeated WD40 motifs act as a site for protein-protein interaction, and proteins containing WD40 repeats are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins. The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are G proteins (beta subunit is a beta-propeller), TAFII transcription factor, and E3 ubiquitin ligase [(PUBMED:11814058), (PUBMED:10322433)]. In Arabidopsis spp., several WD40-containing proteins act as key regulators of plant-specific developmental events.
|GO function:||protein binding (GO:0005515)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a WD40 domain in a specific node, click on it.
This tree shows only several representative species. The complete taxonomic breakdown of all proteins with WD40 domain is also avaliable.
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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
- Cellular role (predicted cellular role)
Cellular role: signalling
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Garcia-Higuera I et al.
- Folding of proteins with WD-repeats: comparison of six members of the WD-repeat superfamily to the G protein beta subunit.
- Biochemistry. 1996; 35: 13985-94
- Display abstract
The family of WD-repeat proteins comprises over 30 different proteins that share a highly conserved repeating motif [Neer, E. J., Schmidt, C. J., Nambudripad, R., & Smith, T. F. (1994) Nature 371, 297-300]. Members of this family include the signal-transducing G protein beta subunit, as well as other proteins that regulate signal transduction, transcription, pre-mRNA splicing, cytoskeletal organization, and vesicular fusion. The crystal structure of one WD-repeat protein (G beta) has now been solved (Wall et al., 1995; Sondek et al, 1996) and reveals that the seven repeating units form a circular, propeller-like structure with seven blades each made up of four beta strands. It is very likely that all WD-repeat proteins form a similar structure. If so, it will be possible to use information about important surface regions of one family member to predict properties of another. If WD proteins form structures similar to G beta, their hydrodynamic properties should be those of compact, globular proteins, and they should be resistant to cleavage by trypsin. However, the only studied example of a WD-repeat protein, G beta, synthesized in vitro in a rabbit reticulocyte lysate, is unable to fold into a native structure without its partner protein G gamma. The non-WD-repeat amino terminal alpha helix of G beta does not inhibit folding because G beta does not fold even when this region is removed. It is not known whether all WD-repeat proteins are unable to fold when synthesized in an in vitro system. We synthesized seven members of the family in a rabbit reticulocyte lysate, determined their Stokes radius, sedimentation coefficient, and frictional ratio, and assayed their stability to trypsin. Our working definition of folding was that the proteins from globular, trypsin-resistant structures because, except for G beta gamma, their functions are not known or cannot be assayed in reticulocyte lysates. We chose proteins that include amino and carboxyl extensions as well as proteins that are made up entirely of WD-repeats. We show that unlike G beta, several proteins with WD-repeats are able to fold into globular proteins in a rabbit reticulocyte lysate. One protein, beta Trcp, formed large aggregates like G beta, suggesting that it may also require a partner protein. Despite the presence of many potential tryptic cleavage sites, all of the proteins that did fold gave stable large products on tryptic proteolysis, as predicted on the basis of the structure of G beta. These studies suggest that other WD-repeat proteins are likely to form propeller structures similar to G beta.
- Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB
- Crystal structure of a G-protein beta gamma dimer at 2.1A resolution.
- Nature. 1996; 379: 369-74
- Display abstract
Many signalling cascades use seven-helical transmembrane receptors coupled to heterotrimeric G proteins (G alpha beta gamma) to convert extracellular signals into intracellular responses. Upon nucleotide exchange catalysed by activated receptors, heterotrimers dissociate into GTP-bound G alpha subunits and G beta gamma dimers, either of which can modulate many downstream effectors. Here we use multiwavelength anomalous diffraction data to solve the crystal structure of the beta gamma dimer of the G protein transducin. The beta-subunit is primarily a seven-bladed beta-propeller that is partially encircled by an extended gamma-subunit. The beta-propeller, which contains seven structurally similar WD repeats, defines the stereochemistry of the WD repeat and the probable architecture of all WD-repeat-containing domains. The structure details interactions between G protein beta- and gamma-subunits and highlights regions implicated in effector modulation for the conserved family of G protein beta gamma dimers.
- Dynlacht BD, Weinzierl RO, Admon A, Tjian R
- The dTAFII80 subunit of Drosophila TFIID contains beta-transducin repeats.
- Nature. 1993; 363: 176-9
- Display abstract
A key component of the RNA polymerase II transcriptional apparatus, TFIID, is a multi-protein complex containing the TATA box-binding protein (TBP) and at least seven tightly associated factors (TAFs). Although the functions of most TFIID subunits are unknown, it is clear that TAFs are not necessary for basal activity but that one or more are required for regulated transcription, and so behave as coactivators. The presence of multiple subunits indicates that there is an intricate assembly process and that TAFs may be responsible for other activities. We have described the properties of the subunit dTAFII110, which can interact directly with the transcriptional activator Sp1 (ref. 5). In addition, the largest subunit, dTAFII250, binds directly to TBP and links other TAFs to the complex. Here we describe the cloning, expression and partial characterization of the Drosophila TAF of M(r) 80,000, dTAFII80. Sequence analysis reveals that dTAFII80 contains several copies of the WD40 (beta-transducin) repeat. Moreover, dTAFII80 shares extended sequence similarity with an Arabidopsis gene, COP1, which encodes a putative transcription factor that is though to regulate development. We have expressed recombinant dTAFII80 and begun to characterize its interaction with other members of the TFIID complex. Purified recombinant dTAFII80 is unable to bind TBP directly or to interact strongly with the C-terminal domain of dTAFII250 (delta N250). Instead, dTAFII80 is only able to recognize and interact with a higher-order complex containing TBP, delta N250, 110 and 60. These findings suggest the formation of TFIID may require an ordered assembly of the TAFs, some of which bind directly to TBP and others that are tethered to the complex as a result of specific TAF/TAF interactions.
- Fong HK et al.
- Repetitive segmental structure of the transducin beta subunit: homology with the CDC4 gene and identification of related mRNAs.
- Proc Natl Acad Sci U S A. 1986; 83: 2162-6
- Display abstract
Retinal transducin, a guanine nucleotide regulatory protein (referred to as a G protein) that activates a cGMP phosphodiesterase in photoreceptor cells, is comprised of three subunits. We have identified and analyzed cDNA clones of the bovine transducin beta subunit that may be highly conserved or identical to that in other G proteins. From the cDNA nucleotide sequence of the entire coding region, the primary structure of a 340-amino acid protein was deduced. The encoded beta subunit has a Mr of 37,375 and is comprised of repetitive homologous segments arranged in tandem. Furthermore, significant homology in primary structure and segmental sequence exists between the beta subunit and the yeast CDC4 gene product. The Mr 37,375 beta subunit polypeptide is encoded by a 2.9-kilobase (kb) mRNA. However, there exists in retina other beta-related mRNAs that are divergent from the 2.9-kb mRNA on the basis of oligonucleotide and primer-extended probe hybridizations. All mammalian tissues and clonal cell lines that have been examined contain at least two beta-related mRNAs, usually 1.8 and 2.9 kb in length. These results suggest that the mRNAs are the processed products of a small number of closely related genes or of a single highly complex beta gene.
- Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the WD40 domain.
Protein Disease Peroxisomal targeting signal 2 receptor (O00628) (SMART) OMIM:601757: Rhizomelic chondrodysplasia punctata, type 1
Platelet-activating factor acetylhydrolase IB subunit alpha (P43034) (SMART) OMIM:601545: Lissencephaly-1 ; Subcortical laminar heterotopia
OMIM:247200: Miller-Dieker lissencephaly syndrome
DNA damage-binding protein 2 (Q92466) (SMART) OMIM:600811: Xeroderma pigmentosum, group E, DDB-negative subtype
- Metabolism (metabolic pathways involving proteins which contain this domain)
Click the image to view the interactive version of the map in iPath
% proteins involved KEGG pathway ID Description 15.71 map04120 Ubiquitin mediated proteolysis 10.79 map04111 Cell cycle - yeast 9.05 map04310 Wnt signaling pathway 7.06 map04110 Cell cycle 6.13 map04530 Tight junction 4.93 map04810 Regulation of actin cytoskeleton 4.53 map04150 mTOR signaling pathway 3.99 map03022 Basal transcription factors 3.99 map04350 TGF-beta signaling pathway 3.99 map04730 Long-term depression 3.60 map04115 p53 signaling pathway 2.66 map04340 Hedgehog signaling pathway 2.53 map04140 Regulation of autophagy 2.40 map04080 Neuroactive ligand-receptor interaction 2.13 map04914 Progesterone-mediated oocyte maturation 2.00 map04910 Insulin signaling pathway 1.60 map00565 Ether lipid metabolism 1.46 map04742 Taste transduction 1.46 map04210 Apoptosis 1.33 map05222 Small cell lung cancer 1.33 map00632 Benzoate degradation via CoA ligation 0.93 map00562 Inositol phosphate metabolism 0.40 map00350 Tyrosine metabolism 0.40 map00340 Histidine metabolism 0.40 map00642 Ethylbenzene degradation 0.40 map00564 Glycerophospholipid metabolism 0.40 map00960 Alkaloid biosynthesis II 0.40 map00903 Limonene and pinene degradation 0.40 map00310 Lysine degradation 0.40 map00360 Phenylalanine metabolism 0.40 map00624 1- and 2-Methylnaphthalene degradation 0.40 map00380 Tryptophan metabolism 0.27 map00910 Nitrogen metabolism 0.27 map05210 Colorectal cancer 0.13 map04370 VEGF signaling pathway 0.13 map04662 B cell receptor signaling pathway 0.13 map04020 Calcium signaling pathway 0.13 map04720 Long-term potentiation 0.13 map03060 Protein export 0.13 map04360 Axon guidance 0.13 map04010 MAPK signaling pathway 0.13 map00100 Biosynthesis of steroids 0.13 map00561 Glycerolipid metabolism 0.13 map02010 ABC transporters - General 0.13 map04660 T cell receptor signaling pathway 0.13 map00230 Purine metabolism 0.13 map04330 Notch signaling pathway 0.13 map04650 Natural killer cell mediated cytotoxicity
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with WD40 domain which could be assigned to a KEGG orthologous group, and not all proteins containing WD40 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of WD40 domains in PDB
PDB code Main view Title 1a0r Heterotrimeric complex of phosducin/transducin beta-gamma 1b9x Structural analysis of phosducin and its phosphorylation- regulated interaction with transducin 1b9y Structural analysis of phosducin and its phosphorylation- regulated interaction with transducin beta-gamma 1erj Crystal structure of the c-terminal wd40 domain of tup1 1gg2 G protein heterotrimer mutant gi_alpha_1(g203a) beta_1 gamma_2 with gdp bound 1got Heterotrimeric complex of a gt-alpha/gi-alpha chimera and the gt-beta-gamma subunits 1gp2 G protein heterotrimer gi_alpha_1 beta_1 gamma_2 with gdp bound 1gxr Wd40 region of human groucho/tle1 1k8k Crystal structure of arp2/3 complex 1nex Crystal structure of scskp1-sccdc4-cpd peptide complex 1nr0 Two seven-bladed beta-propeller domains revealed by the structure of a c. elegans homologue of yeast actin interacting protein 1 (aip1). 1omw Crystal structure of the complex between g protein-coupled receptor kinase 2 and heterotrimeric g protein beta 1 and gamma 2 subunits 1p22 Structure of a beta-trcp1-skp1-beta-catenin complex: destruction motif binding and lysine specificity on the scfbeta-trcp1 ubiquitin ligase 1pev Crystal structure of the actin interacting protein from caenorhabditis elegans 1pgu Yeast actin interacting protein 1 (aip1), se-met protein, monoclinic crystal form 1pi6 Yeast actin interacting protein 1 (aip1), orthorhombic crystal form 1r5m Crystal structure of the c-terminal wd40 domain of sif2 1s4u Crystal structure analysis of the beta-propeller protein ski8p 1sq9 Structure of ski8p, a wd repeat protein involved in mrna degradation and meiotic recombination 1tbg Beta-gamma dimer of the heterotrimeric g-protein transducin 1trj Homology model of yeast rack1 protein fitted into 11.7a cryo-em map of yeast 80s ribosome 1tyq Crystal structure of arp2/3 complex with bound atp and calcium 1u2v Crystal structure of arp2/3 complex with bound adp and calcium 1u4c Structure of spindle checkpoint protein bub3 1vyh Paf-ah holoenzyme: lis1/alfa2 1xhm The crystal structure of a biologically active peptide (sigk) bound to a g protein beta:gamma heterodimer 1yfq High resolution s. cerevisiae bub3 mitotic checkpoint protein 2aq5 Crystal structure of murine coronin-1 2b4e Crystal structure of murine coronin-1: monoclinic form 2bcj Crystal structure of g protein-coupled receptor kinase 2 in complex with galpha-q and gbetagamma subunits 2ce8 An eh1 peptide bound to the groucho-tle wd40 domain. 2ce9 A wrpw peptide bound to the groucho-tle wd40 domain. 2cnx Wdr5 and histone h3 lysine 4 dimethyl complex at 2.1 angstrom 2co0 Wdr5 and unmodified histone h3 complex at 2.25 angstrom 2g99 Structural basis for the specific recognition of methylated histone h3 lysine 4 by the wd-40 protein wdr5 2g9a Structural basis for the specific recognition of methylated histone h3 lysine 4 by the wd-40 protein wdr5 2gnq Structure of wdr5 2h13 Crystal structure of wdr5/histone h3 complex 2h14 Crystal of wdr5 (apo-form) 2h68 Histone h3 recognition and presentation by the wdr5 module of the mll1 complex 2h6k Histone h3 recognition and presentation by the wdr5 module of the mll1 complex 2h6n Histone h3 recognition and presentation by the wdr5 module of the mll1 complex 2h6q Histone h3 recognition and presentation by the wdr5 module of the mll1 complex 2h9l Wdr5delta23 2h9m Wdr5 in complex with unmodified h3k4 peptide 2h9n Wdr5 in complex with monomethylated h3k4 peptide 2h9p Wdr5 in complex with trimethylated h3k4 peptide 2hes Cytosolic iron-sulphur assembly protein- 1 2i3s Bub3 complex with bub1 glebs motif 2i3t Bub3 complex with mad3 (bubr1) glebs motif 2o9k Wdr5 in complex with dimethylated h3k4 peptide 2oit Crystal structure of the n-terminal domain of the human proto-oncogene nup214/can 2ovp Structure of the skp1-fbw7 complex 2ovq Structure of the skp1-fbw7-cyclinedegc complex 2ovr Structure of the skp1-fbw7-cyclinedegn complex 2p9i Crystal structure of bovine arp2/3 complex co-crystallized with adp and crosslinked with gluteraldehyde 2p9k Crystal structure of bovine arp2/3 complex co-crystallized with atp and crosslinked with glutaraldehyde 2p9l Crystal structure of bovine arp2/3 complex 2p9n Crystal structure of bovine arp2/3 complex co-crystallized with adp 2p9p Crystal structure of bovine arp2/3 complex co-crystallized with adp 2p9s Structure of bovine arp2/3 complex co-crystallized with atp/mg2+ 2p9u Crystal structure of bovine arp2/3 complex co-crystallized with amp-pnp and calcium 2pbi The multifunctional nature of gbeta5/rgs9 revealed from its crystal structure 2pm6 Crystal structure of yeast sec13/31 edge element of the copii vesicular coat, native version 2pm7 Crystal structure of yeast sec13/31 edge element of the copii vesicular coat, selenomethionine version 2pm9 Crystal structure of yeast sec13/31 vertex element of the copii vesicular coat 2qns Crystal structure of the g-protein betagamma subunit bound to a c-terminal region of the pth1 parathyroid hormone receptor 2qxv Structural basis of ezh2 recognition by eed 2trc Phosducin/transducin beta-gamma complex 2vdu Structure of trm8-trm82, the yeast trna m7g methylation complex 2zkq Structure of a mammalian ribosomal 40s subunit within an 80s complex obtained by docking homology models of the rna and proteins into an 8.7 a cryo-em map 3bg0 Architecture of a coat for the nuclear pore membrane 3bg1 Architecture of a coat for the nuclear pore membrane 3c99 Structural basis of histone h4 recognition by p55 3c9c Structural basis of histone h4 recognition by p55 3cfs Structural basis of the interaction of rbap46/rbap48 with histone h4 3cfv Structural basis of the interaction of rbap46/rbap48 with histone h4 3cik Human grk2 in complex with gbetagamma subunits 3dm0 Maltose binding protein fusion with rack1 from a. thaliana 3dw8 Structure of a protein phosphatase 2a holoenzyme with b55 subunit 3dwl Crystal structure of fission yeast arp2/3 complex lacking the arp2 subunit 3dxk Structure of bos taurus arp2/3 complex with bound inhibitor ck0944636 3dxm Structure of bos taurus arp2/3 complex with bound inhibitor ck0993548 3eg6 Structure of wdr5 bound to mll1 peptide 3ei1 Structure of hsddb1-drddb2 bound to a 14 bp 6-4 photoproduct containing dna-duplex 3ei2 Structure of hsddb1-drddb2 bound to a 16 bp abasic site containing dna-duplex 3ei3 Structure of the hsddb1-drddb2 complex 3ei4 Structure of the hsddb1-hsddb2 complex 3emh Structural basis of wdr5-mll interaction 3ewe Crystal structure of the nup85/seh1 complex 3f3f Crystal structure of a nucleoporin complex, space group p21 3f3g Crystal structure of a nucleoporin complex, space group p212121 3f3p Crystal structure of a nucleoporin complex, space group p21212 3fhc Crystal structure of human dbp5 in complex with nup214 3fm0 Crystal structure of wd40 protein ciao1 3fmo Crystal structure of the nucleoporin nup214 in complex with the dead-box helicase ddx19 3fmp Crystal structure of the nucleoporin nup214 in complex with the dead-box helicase ddx19 3frx Crystal structure of the yeast orthologue of rack1, asc1. 3gfc Crystal structure of histone-binding protein rbbp4 3gre Crystal structure of saccharomyces cerevisiae vps15 wd repeat domain 3i2n Crystal structure of wd40 repeats protein wdr92 3iiw Crystal structure of eed in complex with a trimethylated histone h3k27 peptide 3iiy Crystal structure of eed in complex with a trimethylated histone h1k26 peptide 3ij0 Crystal structure of eed in complex with a trimethylated histone h3k9 peptide 3ij1 Crystal structure of eed in complex with a trimethylated histone h4k20 peptide 3ijc Crystal structure of eed in complex with ndsb-195 3iko Crystal structure of the heterotrimeric sec13-nup145c-nup84 nucleoporin complex 3jpx Eed: a novel histone trimethyllysine binder within the eed- ezh2 polycomb complex 3jro Nup84-nup145c-sec13 edge element of the npc lattice 3jrp Sec13 with nup145c (aa109-179) insertion blade
- Links (links to other resources describing this domain)
PFAM WD40 INTERPRO IPR001680 PROSITE WD_REPEATS