Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2008) Nucleic Acids Res , doi:10.1093/nar/gkn808

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WD40 WD40 repeats

There are 107861 WD40 domains in 20307 proteins in SMART's nrdb database.

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.

  Useful shortcuts: Expand all nodes or Collapse tree
  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 (SRS)(SMART)	OMIM:601757: Rhizomelic chondrodysplasia punctata, type 1 OMIM:215100:
  Platelet-activating factor acetylhydrolase IB subunit alpha (SRS)(SMART)	OMIM:601545: Lissencephaly-1 ; Subcortical laminar heterotopia OMIM:247200: Miller-Dieker lissencephaly syndrome
  DNA damage-binding protein 2 (SRS)(SMART)	OMIM:600811: Xeroderma pigmentosum, group E, DDB-negative subtype OMIM:278740:

• 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
  3dm0
  3dw8
  3dwl
  3dxk
  3dxm
  3eg6
  3ei1
  3ei2
  3ei3
  3ei4
  3emh
  3ewe
  3f3f
  3f3g
  3f3p
  3fhc
  3fm0
  3fmo
  3fmp
  3frx
  3gfc
  3gre
  3i2n
  3iiw
  3iiy
  3ij0
  3ij1
  3ijc
  3iko
  3jpx
  3jro
  3jrp

• Links (links to other resources describing this domain)

• PFAM	WD40
  INTERPRO	IPR001680
  PROSITE	WD_REPEATS