Abstract
The WW domain, also known as WWP, or rsp5 domain, is a ~40 amino acid module which was identified in late 1994 by three different groups (Bork and Sudol 1994; André and Springael 1994; Hofmann and Bucher 1995). The name WW or WWP is based on the primary sequence of the domain, which includes two highly conserved tryptophans and an invariant proline. Like several other protein:protein or protein:lipid interaction domains, WW domains have been detected in numerous unrelated proteins, often alongside other domains, and often in multiple copies (reviewed in Staub and Rotin 1996) (Fig. 1). The most noted examples of WW-containing proteins are Nedd4 (neuronal precursor cell expressed developmentally downregulated) and its yeast homologues rsp5 and publ, YAP (yes associated protein), dystrophin, FE65, ess 1/dodo/pin 1, CD45AP (CD45 associated protein), formin binding proteins (FBPs), and several other less well characterized proteins (Figs. 1, 2). The presence of more than one WW domain in some of these proteins (e.g., Nedd4) suggests they interact with multiple targets. Phylogenetic analysis of the various WW domains reveals in some cases greater relatedness between WW domains from different proteins than those within the same protein (Sudol et al. 1995), implicating divergent origin. As is elucidated below, the WW domain is a proteimprotein interaction module which likely functions in an analogous (yet distinct) fashion to SH3 domains.
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References
André B, Springael J-Y (1994) 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 205:1201–1205
Borg JP, Ooi J, Levy E, Margolis B (1996) The phosphotyrosine interaction domains of XI1 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Mol Cell Biol 16:6229–6241
Bork P, Margolis B (1995) A phosphotyrosine interaction domain. Cell 80:693–694
Bork P, Sudol M (1994) The WW domain: a signalling site in dystrophin. Trends Biochem Sci 19:531–533
Bradford MT, Chan DC, Leder P (1997) FBP WW domains and the abl SH3 domain bind to a specific class of proline-rich ligands. EMBO J 16:2376–2383
Bruyns E, Hendricks-Taylor LR, Meuer S, Koretzky GA, Schraven B (1995) Identification of the sites of interaction between lymphocyte phosphatase-associated phosphoprotein (LPAP) and CD45. J Biol Chem 270:31372–31376
Chan DC, Bedford MT, Leder P (1996) Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains. EMBO J 15:1045–1054
Chen HI, Sudol M (1995) The WW domain of Yes-associated protein binds a novel proline-rich ligand that differs from the consensus established for SH3-binding modules. Proc Natl Acad Sci USA 92:7819–7823
Ciechanover A (1994) The ubiquitin-proteasome proteolytic pathway. Cell 79:13–21
De Strooper B, Umans L, Van Lauven F, Van Den Berghe H (1993) Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway J Cell Biol 121:295–304
Duilio A, Zambrano N, Mogavero AR, Ammendola R, Cimino F, Russo T (1991) A rat brain NA encoding a transcriptional activator homologous to the DNA binding domain of retroviral integrases. Nucleic Acids Res 19:5269–5274
Einbond A, Sudol M (1996) Towards prediction of cognate complexes between the WW domain and proline-rich ligands. FEBS Lett 384:1–8
Eppert K, Scherer SW, Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui L-C, Bapat B, Gallinger S, Andrulis IL, Thomsen GH, Wrana JL, Attisano L (1996) MADR2 maps to 18q21 and encodes a TGFβ-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell 86:543–552
Feng S, Chen JK, Yu H, Simon JA, Schreiber SL (1994) Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions. Science 266:1241–1247
Fiore F, Zambrano N, Minopoli G, Donini V, Duilio A, Russo T (1995) The regions of the Fe65 protein homologous to the phosphotyrosine interaction/phosphotyrosine binding domain of She bind the intracellular domain of Alzheimer’s amyloid precursor protein. J Biol Chem 270:30853–30856
Firsov D, Schild L, Gautschi I, Merillat AM, Schneeberger E, Rossier B (1996) Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. Proc Natl Acad Sci USA 93:15370–15375
Galan JM, Volland C, Grimal DU, Haguenauer-Tsapis R (1994) The yeast plasma membrane uracil permease is stabilized against stress-induced degradation by a point mutation in a cyclin-like destruction box. Biochem Biophys Res Commun 201:769–775
Galan JM, Moreau V, Andre B, Volland C, Haguenauer-Tsapis R (1996) Ubiquitination mediated by the Npilp/Rsp5p ubiquitin-protein ligase is required for endocytosis of the yeast uracil permease. J Biol Chem 271:10946–10952
Garnier L, Wills JW, Verderame MF, Sudol M (1996) WW domains and retroviral budding. Nature 381:744–745(correspondence)
Grenson M (1992) Amino acid transporters in yeast: structure, function and regulation. In: De Pont JML (ed) Molecular aspects of transport proteins. Elsevier Science, Amsterdam, pp 219–245
Guénette SY, Chen J, Jondro PD, Tanzi RE (1996) Association of a novel human FEG5-like protein with the cytoplasmic domain of the p-amyloid precursor protein. Proc Natl Acad Sci USA 93:10832–10837
Hanes SD, Shank PR, Bostian KA (1989) Sequence and mutational analysis of ESS1, a gene essential for growth in Saccharomyces cerevisae. Yeast 5:55–72
Hani J, Stumf G, Domdey H (1995) PTF1 encodes an essential protein in Saccharomyces cerevisiae, which shows strong homology with a new putative family of ppl-ases. FEBS Lett 365:198–202
Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets RA, Lu Y, Canessa C, Iwasaki T, Rossier BC, Lifton RP (1995a) Hypertension caused by a truncated epithelial sodium channel gamma sub-unit: genetic heterogeneity of Liddle syndrome. Nature Genet 11:76–82
Hansson JH, Schild L, Lu Y, Wilson TA, Gautschi I, Shimkets RA, Nelson-Williams C, Rossier BC, Lifton RP (1995b) A de novo missense mutation of the β subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. Proc Natl Acad Sci USA 25:11495–11499
Hein C, Springael JH, Volland C, Haguenauer-Tsapis R, Andre B (1995) NPI1, an essential yeast gene involved in induced degradation of Gapl and Fur4 permeases, encodes the Rsp5 ubiquitin-protein ligase. Mol Microbiol 18:77–87
Hochstrasser M (1996) Protein degradation or regulation: Ub the judge. Cell 84:813–815
Hofmann K, Bucher P (1995) The rsp5-domain is shared by proteins of diverse functions. FEBS Lett 358:153–157
Huibregtse JM, Scheffner M, Beaudenon S, Howley PM (1995) A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci USA 92:2563–2567
Ibraghimov-Beskrovnaya O, Milatovich A, Ozcelik T, Yang B, Koepnick K, Francke U, Campbell KP (1993) Human dystroglycan: skeletal muscle NA, genomic structure, origin of tissue specific iso-forms and chromosomal localization. Hum Mol Genet 2:1651–1657
Jauniaux J C, Grenson M (1990) GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression. Eur J Biochem 190:39–44
Jund R, Weber E, Chevallier MR (1988) Primary structure of the uracil transport protein of Saccharomyces cerevisiae. Eur J Biochem 171:417–424
Jung D, Yang B, Meyer J, Chamberlain JS, Campbell KP (1995) Identification and characterization of the dystrophin anchoring site on p-dystroglycan. J Biol Chem 270:27305–27310
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Muller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell surface receptor. Nature 325:733–736
Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM (1987) Complete cloning of the Duchenne muscular dystrophy (DMD) NA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50:509–515
Kraut R, Ortega J A (1996) Inscuteable, a neural precursor gene of Drosophila, encodes a candidate for cytoskeleton adaptor protein. Dev Biol 174:65–81
Kraut R, Chia W, Jan LY, Jan YN, Knoblich JA (1996) Role of inscuteable in orienting asymmetric cell divisions in Drosophila. Nature 383:50–55
Koo EH, Squazzo SL (1994) Evidence that production and release of amyloid (3-protein involves the endocytic pathway. J Biol Chem 269:17386–17389
Kumar S, Tomooka Y, Noda M (1992) Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem Biophys Res Commun 185:1155–1161
Liddle GW, Bledsoe T, Coppage WS Jr (1963) A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Physicians 76:199–213
Liu F, Hata A, Baker JC, Doody J, CĂ¡rcamo J, Harland RM, MassaguĂ© J (1996) A human Mad protein acting as a BMP-regulated transcriptional activator. Nature 381:620–623
Lu KP, Hunter T (1995) Evidence for a NIMA-like mitotic pathway in vertebrate cells. Cell 81:413–424
Lu KP, Hanes SD, Hunter T (1996) A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature 380:544–547
Macias MJ, Hyvonen M, Baraldi E, Schultz J, Sudol M, Saraste M, Oschkinat H (1996) Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide. Nature 382:646–649
Maleszka R, Hanes SD, Hackett RL, De Conet HG, Gabor-Miklos GL (1996) The Drosophila mela-nogaster dodo (dod) gene, conserved in humans, is functionally interchangeable with the ESS1 cell division gene of Sacchromyces cerevisiae. Proc Natl Acad Sci USA 93:447–451
McDonald FJ, Welsh MJ (1995) Binding of the proline-rich region of the epithelial Na channel to SH3 domains and its association with specific cellular proteins. Biochem J 312:491–497
McFarland EDC, Thomas ML (1995) CD45 protein-tyrosine phosphatase associates with the WW domain-containing protein, CD45AP, through the transmembrane region. J Biol Chem 270:28103–28107
Nefsky B, Beach D (1996) Publ acts as an E6-AP like protein ubiquitin ligase in the degradation of cdc25. EMBO J 15:1301–1312
Ohno S, Kawasaki H, Imajoh S, Suzuki H (1987) Tissue-specific expression of three distinct types of rabbit protein kinase C. Nature 325:161–166
Osmani SA, Pu RT, Morris NR (1988) Mitotic induction and maintenance by overexpression of a G2-specific gene that encodes a potential protein kinase. Cell 53:237–244
Pawson T (1995) Protein modules and signalling networks. Nature 373:573–579
Pingel JT, Thomas ML (1989) Evidence that leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell 58:1055–1065
Pirozzi G, Monnell DM, Uveges AJ, Sparks AB, Carter JM, Kay BK, Fowlkes DM (1996) Identification of novel human WW domain - containing proteins by cloning of ligand targets. Mol Biol Cell 7 (abstract 1991)
Ranganathan R, Lu KP, Hunter T, Noel JP (1997) X-Ray crystal structure and functional properties of the mitotic peptidyl-prolyl isomerase Pinl Cell, (in press)
Rotin D, Baagi D, O’Brodovich H, Merilainen J, Lehto VP, Canessa C, Rossier BC, Downey GP (1994) An SH3 binding region in the epithelial Na channel (aN) mediates its localization at the apical membrane. EMBO J 13:4440–4450
Saleki R, Jia Z, Karagiannis J, Young P (1997) Low tolerance in Schizosaccharomyces pombe requires a functioning publ ubiquitin ligase. Mol Gen Genet 254:520–528
Schild L, Canessa CM, Shimkets RA, Warnock DG, Lifton RP, Rossier BC (1995) A mutation in the epithelial sodium channel causing Liddle’s disease increases channel activity in the Xenopus laevis oocyte expression system. Proc Natl Acad Sci USA 92:5699–5703
Schild L, Lu Y, Gautschi I, Schneeberger E, Lifton RP, Rossier BC (1996) Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome. EMBO J 15:2381–2387
Schraven B, Schoenhaut D, Bruyns E, Koretzky G, Eckerskorn C, Wallich R, Kirchgessner H, Sakorafas P, Labkovsky B, Ratnofsky S, Heuer S (1994) LPAP, a novel 32-kDa phosphoprotein that interacts with CD45 in human lymphocytes. J Biol Chem 269:29102–29111
Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR, Ulick S, Milora RV, Findling JW, Canessa CM, Rossier BC, Lifton RP (1994) Liddle’s syndrome: heritable human hypertension caused by mutations in the p subunit of the epithelial sodium channel. Cell 79:407–414
Snyder PM, Price MP, Monald FJ, Adams CM, Volk KA, Zeiher BG, Stokes JB, Welsh MJ (1995) Mechanism by which Liddle’s syndrome mutations increase activity of a human epithelial Na + channel. Cell 83:969–978
Staub O, Rotin D (1996) WW domains. Structure 4:495–499
Staub O, Dho S, Henry P, Correa J, Ishikawa T, Mlade J, Rotin D (1996) WW domains of Nedd4 bind to the proline-rich PY motifs in epithelial Na channel deleted in Liddle’s syndrome. EMBO J 15:2371–2380
Staub O, Firsov D, Gantschi I, Ishikawa T, Breitschopf K, Ciechanover A, Schild L, Rotin D (1997) Regulation of stability and function of the epithelial Na+ channel (EN) by ubiquitination (submitted)
Sudol M (1994) Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes-oncogene product. Oncogene 9:2145–2152
Sudol M, Chen HI, Bougeret C, Einbond A, Bork P (1995) Characterization of a novel protein-binding module - the WW domain. FEBS Lett 369:67–71
Tamura M, Schild L, Enomoto N, Matsui N, Marumo F, Rossier B, Sasaki S (1996) Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene. J Clin Invest 97:1780–1784
Takeda A, Maizel AL, Kitamura K, Ohta T, Kimura S (1994) Molecular cloning of the CD45-associated 30-kDa protein. J Biol Chem 269:2357–2360
Volland C, Urban-Grimal D, Geraud G, Haguenauer-Tsapis R (1994) Endocytosis and degradation of the yeast uracil permease under adverse conditions. J Biol Chem 269:9833–9841
Weiss A (1993) A cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases. Cell 73:209–212
Worton R (1995) Muscular dystrophies: diseases of the dystrophin-glycoprotein complex. Science 270:755–756
Yang B, Jung D, Motto D, Meyer J, Koretzky G, Campbell KP (1995) SH3 domain-mediated interaction of Dystroglycan and GRB2. J Biol Chem 270:11711–11714
Ye XS, Xu G, Pu RT, Fincher RR, Muire SL, Osmani AH, Osmani SA (1995) The NIMA protein kinase is hyperphosphorylated and activated downstream of p34cdc2/cycli: coordination of two mitosis promoting kinases. EMBO J 14:986–994
Yu H, Chen JK, Feng S, Dalgarno DC, Brauer AW, Schreiber SL (1994) Structural basis for the binding of proline-rich peptides to SH3 domains. Cell 76:933–945
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Rotin, D. (1998). WW (WWP) Domains: From Structure to Function. In: Pawson, A.J. (eds) Protein Modules in Signal Transduction. Current Topics in Microbiology and Immunology, vol 228. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80481-6_5
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