PROSITE documentation PDOC00574

Trp-Asp (WD-40) repeats signature and profiles

β-transducin (G-β) is one of the three subunits (α, β, and γ) of the guanine nucleotide-binding proteins (G proteins) which act as intermediaries in the transduction of signals generated by transmembrane receptors [1]. The α subunit binds to and hydrolyzes GTP; the functions of the β and γ subunits are less clear but they seem to be required for the replacement of GDP by GTP as well as for membrane anchoring and receptor recognition.

In higher eukaryotes G-β exists as a small multigene family of highly conserved proteins of about 340 amino acid residues. Structurally G-β consists of eight tandem repeats of about 40 residues, each containing a central Trp-Asp motif (this type of repeat is sometimes called a WD-40 repeat). Such a repetitive segment has been shown [2,3,4,5] to exist in a number of other proteins listed below:

• Yeast STE4, a component of the pheromone response pathway. STE4 is a G-β like protein that associates with GPA1 (G-α) and STE18 (G-γ).
• Yeast MSI1, a negative regulator of RAS-mediated cAMP synthesis. MSI1 is most probably also a G-β protein.
• Human and chicken protein 12.3. The function of this protein is not known, but on the basis of its similarity to G-β proteins, it may also function in signal transduction.
• Chlamydomonas reinhardtii gblp. This protein is most probably the homolog of vertebrate protein 12.3.
• Human LIS1, a neuronal protein involved in type-1 lissencephaly.
• Mammalian coatomer β' subunit (β'-COP), a component of a cytosolic protein complex that reversibly associates with Golgi membranes to form vesicles that mediate biosynthetic protein transport.
• Yeast CDC4, essential for initiation of DNA replication and separation of the spindle pole bodies to form the poles of the mitotic spindle.
• Yeast CDC20, a protein required for two microtubule-dependent processes: nuclear movements prior to anaphase and chromosome separation.
• Yeast MAK11, essential for cell growth and for the replication of M1 double-stranded RNA.
• Yeast PRP4, a component of the U4/U6 small nuclear ribonucleoprotein with a probable role in mRNA splicing.
• Yeast PWP1, a protein of unknown function.
• Yeast SKI8, a protein essential for controlling the propagation of double- stranded RNA.
• Yeast SOF1, a protein required for ribosomal RNA processing which associates with U3 small nucleolar RNA.
• Yeast TUP1 (also known as AER2 or SFL2 or CYC9), a protein which has been implicated in dTMP uptake, catabolite repression, mating sterility, and many other phenotypes.
• Yeast YCR57c, an ORF of unknown function from chromosome III.
• Yeast YCR72c, an ORF of unknown function from chromosome III.
• Slime mold coronin, an actin-binding protein.
• Slime mold AAC3, a developmentally regulated protein of unknown function.
• Drosophila protein Groucho (formerly known as E(spl); 'enhancer of split'), a protein involved in neurogenesis and that seems to interact with the Notch and Delta proteins.
• Drosophila TAF-II-80, a protein that is tightly associated with TFIID.

The number of repeats in the above proteins varies between 5 (PRP4, TUP1, and Groucho) and 8 (G-β, STE4, MSI1, AAC3, CDC4, PWP1, etc.). In G-β and G-β like proteins, the repeats span the entire length of the sequence, while in other proteins, they make up the N-terminal, the central or the C-terminal section.

A signature pattern can be developed from the central core of the domain (positions 9 to 23).

Two profiles were developed for this module, the first one picks up WD repeats while the second profile is 'circular' and will thus detect a region containing adjacent WD repeats.