{PDOC00574} {PS00678; WD_REPEATS_1} {PS50082; WD_REPEATS_2} {PS50294; WD_REPEATS_REGION} {BEGIN} ************************************************** * Trp-Asp (WD-40) repeats signature and profiles * ************************************************** Beta-transducin (G-beta) is one of the three subunits (alpha, beta, and gamma) of the guanine nucleotide-binding proteins (G proteins) which act as intermediaries in the transduction of signals generated by transmembrane receptors [1]. The alpha subunit binds to and hydrolyzes GTP; the functions of the beta and gamma 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-beta exists as a small multigene family of highly conserved proteins of about 340 amino acid residues. Structurally G-beta 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-beta like protein that associates with GPA1 (G-alpha) and STE18 (G-gamma). - Yeast MSI1, a negative regulator of RAS-mediated cAMP synthesis. MSI1 is most probably also a G-beta protein. - Human and chicken protein 12.3. The function of this protein is not known, but on the basis of its similarity to G-beta 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 beta' subunit (beta'-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-beta, STE4, MSI1, AAC3, CDC4, PWP1, etc.). In G-beta and G- beta 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. -Consensus pattern: [LIVMSTAC]-[LIVMFYWSTAGC]-[LIMSTAG]-[LIVMSTAGC]-x(2)-[DN]- x-{P}-[LIVMWSTAC]-{DP}-[LIVMFSTAG]-W-[DEN]-[LIVMFSTAGCN] -Sequences known to belong to this class detected by the pattern: A majority. This pattern does not detect ALL the occurrences of the domain in any of the above proteins, as some of the copies of the domain are less conserved. -Other sequence(s) detected in Swiss-Prot: 95 other proteins, but in all of them, the pattern is found only ONCE, whereas it is generally found twice or more in WD-repeat proteins. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: 1. -Sequences known to belong to this class detected by the circular profile: ALL -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: December 2004 / Pattern and text revised. [ 1] Gilman A.G. "G proteins: transducers of receptor-generated signals." Annu. Rev. Biochem. 56:615-649(1987). PubMed=3113327; DOI=10.1146/annurev.bi.56.070187.003151 [ 2] Duronio R.J., Gordon J.I., Boguski M.S. "Comparative analysis of the beta transducin family with identification of several new members including PWP1, a nonessential gene of Saccharomyces cerevisiae that is divergently transcribed from NMT1." Proteins 13:41-56(1992). PubMed=1594577 [ 3] van der Voorn L., Ploegh H.L. FEBS Lett. 307:131-134(1992). [ 4] Neer E.J., Schmidt C.J., Nambudripad R., Smith T.F. "The ancient regulatory-protein family of WD-repeat proteins." Nature 371:297-300(1994). PubMed=8090199; DOI=10.1038/371297b0 [ 5] Smith T.F., Gaitatzes C., Saxena K., Neer E.J. "The WD repeat: a common architecture for diverse functions." Trends Biochem. Sci. 24:181-185(1999). 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