PROSITE documentation PDOC00574

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

Description

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 [E1,2,3,4,5] 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.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

WD_REPEATS_2, PS50082Trp-Asp (WD) repeats profile  (MATRIX)
Sequences known to belong to this class detected by the profile: ALL
Other sequence(s) detected in Swiss-Prot: 1.
Domain architecture view of Swiss-Prot proteins matching PS50082
PS50082
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
Retrieve the sequence logo from the alignment
Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50082
Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50082
Scan Swiss-Prot/TrEMBL entries against PS50082
view ligand binding statistics
Matching PDB structures: 1A0R 1B9X 1B9Y 1ERJ ... [ALL]
WD_REPEATS_REGION, PS50294Trp-Asp (WD) repeats circular profile  (MATRIX)
Sequences known to belong to this class detected by the circular profile: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
Domain architecture view of Swiss-Prot proteins matching PS50294
PS50294
Scan Swiss-Prot/TrEMBL entries against PS50294
view ligand binding statistics
Matching PDB structures: 1A0R 1B9X 1B9Y 1ERJ ... [ALL]
WD_REPEATS_1, PS00678Trp-Asp (WD) repeats signature  (PATTERN)
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.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
Retrieve the sequence logo from the alignment
Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00678
Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00678
Scan Swiss-Prot/TrEMBL entries against PS00678
view ligand binding statistics
Matching PDB structures: 1A0R 1B9X 1B9Y 1ERJ ... [ALL]

References

1 Authors Gilman A.G.
Title G proteins: transducers of receptor-generated signals.
Source Annu. Rev. Biochem. 56:615-649(1987).
PubMed ID 3113327
DOI 10.1146/annurev.bi.56.070187.003151
2 Authors Duronio R.J., Gordon J.I., Boguski M.S.
Title 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.
Source Proteins 13:41-56(1992).
PubMed ID 1594577
3 Authors van der Voorn L., Ploegh H.L.
Source FEBS Lett. 307:131-134(1992).
4 Authors Neer E.J., Schmidt C.J., Nambudripad R., Smith T.F.
Title The ancient regulatory-protein family of WD-repeat proteins.
Source Nature 371:297-300(1994).
PubMed ID 8090199
DOI 10.1038/371297b0
5 Authors Smith T.F., Gaitatzes C., Saxena K., Neer E.J.
Title The WD repeat: a common architecture for diverse functions.
Source Trends Biochem. Sci. 24:181-185(1999).
PubMed ID 10322433
E1
Source http://bmerc-www.bu.edu/projects/wdrepeat/

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