Psychiatry related information on NEDD4

• In searching for candidate genes for bipolar disorder on chromosome 18q21, a novel gene homologous to NEDD4 (Neural precursor cells expressed developmentally down-regulated) was identified using exon trapping and cDNA cloning [1].

High impact information on NEDD4

• Here, we demonstrate that PMEPA1 protein through its PY motifs interacts with WW domains of the human NEDD4 protein [2].
• Both NEDD4 and Itch participate in the degradation of Melan-A [3].
• TSG101 is known to function downstream of NEDD4, sorting ubiquitinated substrates into multivesicular bodies (MVBs), which then deliver their cargo into the lysosomal lumen for degradation [4].
• We examine three CMT1C-associated SIMPLE mutations and show that they do not affect the interaction with NEDD4 or TSG101, nor do they lead to altered subcellular localization [4].
• NEDD4L contains the WW and HECT domains seen in the NEDD4 gene family, but lacks the C2 domain in the N-terminus [1].

Anatomical context of NEDD4

• Given the interaction with NEDD4 and TSG101, and the localization of SIMPLE along the lysosomal degradation pathway, we hypothesize that SIMPLE plays a role in the lysosomal sorting of plasma membrane proteins [4].
• A similar C2 domain in the paralogous NEDD4 gene plays a significant role in the transfer of its product to the apical membrane of epithelial cells [5].

Associations of NEDD4 with chemical compounds

• Taken together, PMEPA1 negatively regulates growth of androgen responsive or refractory CaP cells, and these functions may be mediated through the interaction of PMEPA1 with the NEDD4 protein involved in the ubiquitin-proteasome pathway [2].
• During the search for interacting molecules with the COOH-terminal proline-rich region of p73, we identified a novel NEDD4-related protein (termed as NEDL2) which contains a C2 domain at its NH(2)-terminus, two WW domains, and a HECT domain at its COOH-terminus [6].

References