The domain within your query sequence starts at position 56 and ends at position 102; the E-value for the WD40 domain shown below is 1.59e1.

DMKSCATFSSSHRYHKLIWGPHKMDSKGDVSGVLIAGGENGNIILYD

WD40

WD40 repeats

• 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)

There are 182126 WD40 domains in 33650 proteins in SMART's nrdb database.

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

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

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

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

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 OMIM:215100:
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 OMIM:278740:

Metabolism (metabolic pathways involving proteins which contain this domain)

% 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	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