WWP1

WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. In neurons, murine ortholog Wwp1 and its homolog Wwp2 control polarity acquisition, formation, and branching of axons, as well as migration of newly born nerve cells into the cortical plate.{{cite journal | vauthors = Ambrozkiewicz MC, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, Rusanova A, Altas B, Piepkorn L, Bessa P, Schaub T, Zhang X, Rabe T, Ripamonti S, Rosário M, Akiyama H, Jahn O, Kobayashi T, Hoshino M, Tarabykin V, Kawabe H | title = Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140 | journal = Neuron | volume = 100 | issue = 5 | pages = 1097–1115.e15 | date = December 2018 | pmid = 30392800 | doi = 10.1016/j.neuron.2018.10.008 | doi-access = free}}

WWP1 has been shown to interact with:

• CPSF6,{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M|author-link30=Huda Zoghbi | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 }}
• KLF2,{{cite journal | vauthors = Conkright MD, Wani MA, Lingrel JB | title = Lung Krüppel-like factor contains an autoinhibitory domain that regulates its transcriptional activation by binding WWP1, an E3 ubiquitin ligase | journal = J. Biol. Chem. | volume = 276 | issue = 31 | pages = 29299–306 | date = August 2001 | pmid = 11375995 | doi = 10.1074/jbc.M103670200 | doi-access = free }} and
• Reticulon 4{{cite journal | vauthors = Qin H, Pu HX, Li M, Ahmed S, Song J | title = Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration | journal = Biochemistry | volume = 47 | issue = 51 | pages = 13647–58 | date = Dec 2008 | pmid = 19035836 | doi = 10.1021/bi8017976 }}

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• {{cite journal | vauthors = Conkright MD, Wani MA, Lingrel JB | title = Lung Krüppel-like factor contains an autoinhibitory domain that regulates its transcriptional activation by binding WWP1, an E3 ubiquitin ligase. | journal = J. Biol. Chem. | volume = 276 | issue = 31 | pages = 29299–306 | year = 2001 | pmid = 11375995 | doi = 10.1074/jbc.M103670200 | doi-access = free }}
• {{cite journal | vauthors = Flasza M, Gorman P, Roylance R, Canfield AE, Baron M | title = Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein. | journal = Biochem. Biophys. Res. Commun. | volume = 290 | issue = 1 | pages = 431–7 | year = 2002 | pmid = 11779188 | doi = 10.1006/bbrc.2001.6206 }}
• {{cite journal | vauthors = Galinier R, Gout E, Lortat-Jacob H, Wood J, Chroboczek J | title = Adenovirus protein involved in virus internalization recruits ubiquitin-protein ligases. | journal = Biochemistry | volume = 41 | issue = 48 | pages = 14299–305 | year = 2003 | pmid = 12450395 | doi = 10.1021/bi020125b }}
• {{cite journal | vauthors = Verdecia MA, Joazeiro CA, Wells NJ, Ferrer JL, Bowman ME, Hunter T, Noel JP | title = Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase. | journal = Mol. Cell | volume = 11 | issue = 1 | pages = 249–59 | year = 2003 | pmid = 12535537 | doi = 10.1016/S1097-2765(02)00774-8 | doi-access = free }}
• {{cite journal | vauthors = Komuro A, Imamura T, Saitoh M, Yoshida Y, Yamori T, Miyazono K, Miyazawa K | title = Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1). | journal = Oncogene | volume = 23 | issue = 41 | pages = 6914–23 | year = 2004 | pmid = 15221015 | doi = 10.1038/sj.onc.1207885 | s2cid = 7742985 | doi-access = free }}
• {{cite journal | vauthors = Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM | title = Functional proteomics mapping of a human signaling pathway. | journal = Genome Res. | volume = 14 | issue = 7 | pages = 1324–32 | year = 2004 | pmid = 15231748 | pmc = 442148 | doi = 10.1101/gr.2334104 }}
• {{cite journal | vauthors = Seo SR, Lallemand F, Ferrand N, Pessah M, L'Hoste S, Camonis J, Atfi A | title = The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation. | journal = EMBO J. | volume = 23 | issue = 19 | pages = 3780–92 | year = 2005 | pmid = 15359284 | pmc = 522797 | doi = 10.1038/sj.emboj.7600398 }}
• {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network. | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | year = 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}
• {{cite journal | vauthors = Chen C, Sun X, Guo P, Dong XY, Sethi P, Cheng X, Zhou J, Ling J, Simons JW, Lingrel JB, Dong JT | title = Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. | journal = J. Biol. Chem. | volume = 280 | issue = 50 | pages = 41553–61 | year = 2006 | pmid = 16223724 | doi = 10.1074/jbc.M506183200 | doi-access = free }}
• {{cite journal | vauthors = Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 | year = 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 | s2cid = 13709685 | doi-access = free }}
• {{cite journal | vauthors = Flasza M, Nguyen Huu NS, Mazaleyrat S, Clémence S, Villemant C, Clarke R, Baron M | title = Regulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch. | journal = Mol. Membr. Biol. | volume = 23 | issue = 3 | pages = 269–76 | year = 2006 | pmid = 16785210 | doi = 10.1080/09687860600665010 | s2cid = 913524 }}
• {{cite journal | vauthors = Laine A, Ronai Z | title = Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1. | journal = Oncogene | volume = 26 | issue = 10 | pages = 1477–83 | year = 2007 | pmid = 16924229 | pmc = 2997392 | doi = 10.1038/sj.onc.1209924 }}
• {{cite journal | vauthors = Chen C, Sun X, Guo P, Dong XY, Sethi P, Zhou W, Zhou Z, Petros J, Frierson HF, Vessella RL, Atfi A, Dong JT | title = Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer. | journal = Oncogene | volume = 26 | issue = 16 | pages = 2386–94 | year = 2007 | pmid = 17016436 | doi = 10.1038/sj.onc.1210021 | s2cid = 24487179 | doi-access = free }}

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