WW domain
Encyclopedia
The WW domain is a protein domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

 with two highly conserved tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

s that binds proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...

-rich peptide motifs. The WW domain binds to proteins with particular proline-motifs, [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs.

Structure

The WW domain is a short conserved region in a number of unrelated proteins, which folds as a stable, triple stranded beta sheet
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...

. This short domain of approximately 40 amino acids, may be repeated up to four times in some proteins. The name WW or WWP derives from the presence of two signature tryptophan residues that are spaced 20-23 amino acids apart and are present in most WW domains known to date, as well as that of a conserved proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...

. The first tryptophan binds to the C-terminal conserved proline and forms part of the domains small hydrophobic core. It is frequently associated with other domains typical for proteins in signal transduction processes.

Examples

A large variety of proteins containing the WW domain are known. These include; dystrophin, a multidomain cytoskeletal protein; utrophin, a dystrophin-like protein of unknown function; vertebrate YAP protein, substrate of an unknown serine kinase; Mus musculus (Mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...

) NEDD4
NEDD4
E3 ubiquitin-protein ligase NEDD4 also known as neural precursor cell expressed developmentally down-regulated protein 4 is an enzyme that in humans is encoded by the NEDD4 gene....

, involved in the embryonic development and differentiation of the central nervous system; Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

(Baker's yeast) RSP5, similar to NEDD4 in its molecular organization; Rattus norvegicus (Rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

) FE65
APBB1
Amyloid beta A4 precursor protein-binding family B member 1 is a protein that in humans is encoded by the APBB1 gene.-Interactions:APBB1 has been shown to interact with APLP2, TFCP2, LRP1 and Amyloid precursor protein.-Further reading:...

, a transcription-factor activator expressed preferentially in liver; Nicotiana tabacum
Nicotiana tabacum
Nicotiana tabacum, or cultivated tobacco, is a perennial herbaceous plant. It is found only in cultivation, where it is the most commonly grown of all plants in the Nicotiana genus, and its leaves are commercially grown in many countries to be processed into tobacco. It grows to heights between 1...

(Common tobacco) DB10 protein, amongst others.
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