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InterPro: IPR001202 WW/Rsp5/WWP
Protein matches
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UniProtKB Matches: 2606 proteins |
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Accession
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IPR001202 WW_Rsp5_WWP |
Type
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Domain |
Signatures
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InterPro Relationships
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Children
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IPR002349 WW domain
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Found in
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IPR016344 Dystrophin/utrophin
IPR017433 Dystrophin-related protein 2
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GO Term annotation
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Function
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GO:0005515 protein binding
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InterPro annotation
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Entry Details in BioMart
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Abstract
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Synonym(s): Rsp5 or WWP domain
The WW domain is a short conserved region in a number of unrelated proteins, which folds as a stable, triple stranded beta-sheet. This short domain of approximately 40 amino acids, may be repeated up to four times in some proteins [1, 2, 3,
4]. 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 Pro. The WW domain binds to proteins with particular proline-motifs, [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs [5, 6]. It is frequently associated with other domains typical for proteins in signal transduction processes.
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) NEDD-4, involved in the embryonic development and differentiation of the central nervous system; Saccharomyces cerevisiae (Baker's yeast) RSP5, similar to NEDD-4 in its molecular organization; Rattus norvegicus (Rat) FE65, a transcription-factor activator expressed preferentially in liver; Nicotiana tabacum (Common tobacco) DB10 protein, amongst others.
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Structural links
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Database links
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Interactions
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This domain has been experimentally proven to be involved in Protein:Protein interactions. Representative
data is shown with the following
example proteins:
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Example proteins
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O00213 Amyloid beta A4 precursor protein-binding family B member 1
P33203 Pre-mRNA-processing protein PRP40
P34600 WW domain-containing protein ZK1098.1
Q6RHR9 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1
Q9VVI3 E3 ubiquitin-protein ligase Nedd-4
More proteins
Example Proteins Key
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Publications
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1.
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Bork P, Sudol M.
The WW domain: a signalling site in dystrophin?
Trends Biochem. Sci. 19 531-3 1994
[PubMed: 7846762]
http://dx.doi.org/10.1016/0968-0004(94)90053-1
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2.
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Andre B, Springael JY.
WWP, a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes-associated protein YAP65.
Biochem. Biophys. Res. Commun. 205 1201-5 1994
[PubMed: 7802651]
http://dx.doi.org/10.1006/bbrc.1994.2793
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3.
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Hofmann K, Bucher P.
The rsp5-domain is shared by proteins of diverse functions.
FEBS Lett. 358 153-7 1995
[PubMed: 7828727]
http://dx.doi.org/10.1016/0014-5793(94)01415-W
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4.
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Sudol M, Chen HI, Bougeret C, Einbond A, Bork P.
Characterization of a novel protein-binding module--the WW domain.
FEBS Lett. 369 67-71 1995
[PubMed: 7641887]
http://dx.doi.org/10.1016/0014-5793(95)00550-S
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5.
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Chen HI, Sudol M.
The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules.
Proc. Natl. Acad. Sci. U.S.A. 92 7819-23 1995
[PubMed: 7644498]
http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=EBI&pubmedid=7644498&action=stream&blobtype=pdf
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6.
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Macias MJ, Wiesner S, Sudol M.
WW and SH3 domains, two different scaffolds to recognize proline-rich ligands.
FEBS Lett. 513 30-7 2002
[PubMed: 11911877]
http://dx.doi.org/10.1016/S0014-5793(01)03290-2
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Additional Reading
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Ramirez-Espain X, Ruiz L, Martin-Malpartida P, Oschkinat H, Macias MJ.
Structural characterization of a new binding motif and a novel binding mode in group 2 WW domains.
J. Mol. Biol. 373 2007 1255-68
[PubMed: 17915251]
http://dx.doi.org/10.1016/j.jmb.2007.08.052
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Shcherbik N, Kumar S, Haines DS.
Substrate proteolysis is inhibited by dominant-negative Nedd4 and Rsp5 mutants harboring alterations in WW domain 1.
J. Cell. Sci. 115 2002 1041-8
[PubMed: 11870222]
http://jcs.biologists.org/cgi/content/abstract/115/5/1041
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Einbond A, Sudol M.
Towards prediction of cognate complexes between the WW domain and proline-rich ligands.
FEBS Lett. 384 1996 1-8
[PubMed: 8797792]
http://dx.doi.org/10.1016/0014-5793(96)00263-3
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Macias MJ, Hyvonen M, Baraldi E, Schultz J, Sudol M, Saraste M, Oschkinat H.
Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide.
Nature 382 1996 646-9
[PubMed: 8757138]
http://dx.doi.org/10.1038/382646a0
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Meiyappan M, Birrane G, Ladias JA.
Structural basis for polyproline recognition by the FE65 WW domain.
J. Mol. Biol. 372 2007 970-80
[PubMed: 17686488]
http://dx.doi.org/10.1016/j.jmb.2007.06.064
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Zhang Y, Daum S, Wildemann D, Zhou XZ, Verdecia MA, Bowman ME, Lucke C, Hunter T, Lu KP, Fischer G, Noel JP.
Structural basis for high-affinity peptide inhibition of human Pin1.
ACS Chem. Biol. 2 2007 320-8
[PubMed: 17518432]
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Bedford MT, Sarbassova D, Xu J, Leder P, Yaffe MB.
A novel pro-Arg motif recognized by WW domains.
J. Biol. Chem. 275 2000 10359-69
[PubMed: 10744724]
http://dx.doi.org/10.1074/jbc.275.14.10359
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Zarrinpar A, Lim WA.
Converging on proline: the mechanism of WW domain peptide recognition.
Nat. Struct. Biol. 7 2000 611-3
[PubMed: 10932238]
http://dx.doi.org/10.1038/77891
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Kanelis V, Rotin D, Forman-Kay JD.
Solution structure of a Nedd4 WW domain-ENaC peptide complex.
Nat. Struct. Biol. 8 2001 407-12
[PubMed: 11323714]
http://dx.doi.org/10.1038/87562
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Sudol M, Bork P, Einbond A, Kastury K, Druck T, Negrini M, Huebner K, Lehman D.
Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain.
J. Biol. Chem. 270 1995 14733-41
[PubMed: 7782338]
http://dx.doi.org/10.1074/jbc.270.24.14733
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Lu PJ, Zhou XZ, Shen M, Lu KP.
Function of WW domains as phosphoserine- or phosphothreonine-binding modules.
Science 283 1999 1325-8
[PubMed: 10037602]
http://dx.doi.org/10.1126/science.283.5406.1325
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Pastorino L, Sun A, Lu PJ, Zhou XZ, Balastik M, Finn G, Wulf G, Lim J, Li SH, Li X, Xia W, Nicholson LK, Lu KP.
The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production.
Nature 440 2006 528-34
[PubMed: 16554819]
http://dx.doi.org/10.1038/nature04543
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Jennings MD, Blankley RT, Baron M, Golovanov AP, Avis JM.
Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex.
J. Biol. Chem. 282 2007 29032-42
[PubMed: 17656366]
http://dx.doi.org/10.1074/jbc.M703453200
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Jager M, Zhang Y, Bieschke J, Nguyen H, Dendle M, Bowman ME, Noel JP, Gruebele M, Kelly JW.
Structure-function-folding relationship in a WW domain.
Proc. Natl. Acad. Sci. U.S.A. 103 2006 10648-53
[PubMed: 16807295]
http://dx.doi.org/10.1073/pnas.0600511103
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Narimatsu M, Bose R, Pye M, Zhang L, Miller B, Ching P, Sakuma R, Luga V, Roncari L, Attisano L, Wrana JL.
Regulation of planar cell polarity by Smurf ubiquitin ligases.
Cell 137 2009 295-307
[PubMed: 19379695]
http://dx.doi.org/10.1016/j.cell.2009.02.025
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Lin CH, MacGurn JA, Chu T, Stefan CJ, Emr SD.
Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface.
Cell 135 2008 714-25
[PubMed: 18976803]
http://dx.doi.org/10.1016/j.cell.2008.09.025
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Ermekova KS, Zambrano N, Linn H, Minopoli G, Gertler F, Russo T, Sudol M.
The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled.
J. Biol. Chem. 272 1997 32869-77
[PubMed: 9407065]
http://dx.doi.org/10.1074/jbc.272.52.32869
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He J, Bellini M, Inuzuka H, Xu J, Xiong Y, Yang X, Castleberry AM, Hall RA.
Proteomic analysis of beta1-adrenergic receptor interactions with PDZ scaffold proteins.
J. Biol. Chem. 281 2006 2820-7
[PubMed: 16316992]
http://dx.doi.org/10.1074/jbc.M509503200
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