The WWP1 gene encompasses 26 exons which span approximatively 142 kb of DNA. BAC clone RPCI-459L5 contains the complete human WWP1 genome sequence.

WWP1 mRNA is strongly or modestly expressed in human heart, muscle, placenta, kidney, liver, pancreas and testis (Mosser EA, 1998; Komuro A, 2004). The size of the WWP1 mRNA is about 4.2 Kb (Chen C, 2007). There are multiple splicing isoforms in the breast cancer cell line T47D (Flasza M, 2002). The open reading frame for the full length WWP1 gene is 2766 bp. The transcription is increased by TGFb (Chen C, 2007).

922 amino acids; approximatively 110 kDa protein; The C2 domain at N-terminus is responsible for calcium-dependent phospholipid binding. The four WW domains in the middle are responsible for protein-protein interaction with PY motifs. The HECT domain at the C-terminus is responsible for the ubiquitin transfer. The Cystein 890 is the catalytic center. The underlined WWP1 substrates do not have a PY motif (PPXY). A smaller WWP1 protein isoform was detected in two prostate cancer cell lines PC-3 and LAPC-4 (Chen C, 2007).
Protein structure: The HECT domain of WWP1 (see Figure 2C.)(Verdecia MA., 2003).

The WWP1 protein is lowly expressed in normal prostate and breast but is frequently upregulated in prostate and breast cancers due to the gene amplification.

Predominately on membrane structures in cytoplasm and occasionally in nucleus (see Figure 2B.).

WWP1 is an E3 ubiquitin ligase.
WWP1 negatively regulates the transforming growth factor-beta (TGF-b) signaling by targeting its molecular components, including TGF-beta receptor 1 (TbR1) (Komuro A, 2004), Smad2 (Seo SR, 2004), and Smad4 (Moren A., 2005) for ubiquitin mediated degradation.
In addition, WWP1 has been reported to target the epithelial Na+ channel (ENaC) (Malbert-Colas L, 2003), Notch (Shaye DD, 2005), Runx2 (Jones DC, 2006; Shen R, 2006), KLF2 (Zhang X, 2004), and KLF5 (Chen C, 2005) for ubiquitin-mediated proteolysis.
Recently, WWP1 has been demonstrated to inhibit p53 activity through exporting p53 from the nucleus after ubiquitination (Laine A,.2007). Overall, WWP1 may play a pro-survival role in several tumor types including breast (Chen C, 2007) and prostate (Chen C, 2007). WWP1 has also shown to promote virus budding (Martin-Serrano J, 2005; Heidecker G, 2007).

WWP1 belongs to the C2-WW-HECT E3 family which contains 8 other members (Chen C, 2007). The WWP1 gene is highly-conserved among species (from human to c. elegant).

The WWP1 gene is rarely mutated in human prostate cancer (Chen C, 2007). Two sequence alterations were detected in prostate cancer xenografts. One was 2393A-->T (Glu798Val) in CWR91 and the other was 721A-->T (Thr241Ser) in LuCaP35. Additionally, some mutations in the HECT domain decrease the E3 ligase activity (Verdecia MA., 2003).