Disease relevance of UBE3AP2

• Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase [1].
• Cancer-predisposing mutations within the RING domain of BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity [2].
• Mutations in the parkin gene, which encodes for ubiquitin-protein ligase (E3), have been implicated in autosomal recessive juvenile Parkinsonism, an early onset and common familial form of PD [3].

High impact information on UBE3AP2

• These results suggest that a novel conjugating enzyme (possibly a ubiquitin-protein ligase) may be responsible for the degradation of these acetylated proteins by recognizing structural features of the substrate that are downstream and distinct from the NH2-terminal residue [4].
• And in mice, Purkinje cells that express mutant ataxin-1 but not a ubiquitin-protein ligase have significantly fewer NIs [5].
• Nedd4 is a ubiquitin protein ligase (E3) containing a C2 domain, three or four WW domains, and a ubiquitin ligase HECT domain [6].
• The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin-protein ligase that targets for degradation cell-cycle regulatory proteins during exit from mitosis and in the G1 phase of the cell cycle [7].
• Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death [8].

Biological context of UBE3AP2

• We have also mapped two highly homologous processed pseudogenes, UBE3AP1 and UBE3AP2, to chromosomes 2 and 21, respectively, and determined their genomic organization [9].
• We have created PPFINDER (for Processed Pseudogene finder), a program that integrates several methods of processed pseudogene finding in mammalian gene annotations [10].
• Previous studies have indicated that at least part of the selection of proteins for degradation takes place at a binding site on ubiquitin-protein ligase, to which the protein substrate is bound prior to ligation to ubiquitin [11].
• The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7 [12].
• By either transient or stable transfection of Chinese hamster ovary (CHO) Tet-On cells, we successfully expressed, detected, and immobilized biotinylated human Itch, a pleiotropic multi-domain ubiquitin-protein ligase, as well as Gla-RTK, a putative vitamin K-dependent receptor tyrosine kinase [13].

Anatomical context of UBE3AP2

• We have recently shown that a ubiquitin-protein ligase Nedd4 binds via its WW domains to these PY motifs on ENaC, that ENaC is regulated by ubiquitination, and that Xenopus laevis Nedd4 (xNedd4) controls the cell surface pool of ENaC when coexpressed in Xenopus oocytes [14].
• The ubiquitin-protein ligase Nedd4 targets Notch1 in skeletal muscle and distinguishes the subset of atrophies caused by reduced muscle tension [15].
• Turnover of these channels in the cell membrane is mediated by Nedd4-2, a ubiquitin protein ligase; serum- and glucocorticoid-regulated kinase interacts with and phosphorylates Nedd4-2, thereby rendering it unable to bind the sodium channels [16].

Associations of UBE3AP2 with chemical compounds

• Parkin has ubiquitin-protein ligase activity in the presence of UbcH8 [17].
• Inhibition of ubiquitin-protein ligase (E3) by mono- and bifunctional phenylarsenoxides. Evidence for essential vicinal thiols and a proximal nucleophile [18].
• First of all, Parkin was found to be a ubiquitin-protein ligase (E3), a component of the ubiquitin system, which is an important adenosine triphosphate-dependent protein degradation machinery [19].
• The recent success of the proteasome inhibitor Bortezomib (PS-341) for treatment of relapsed, refractory myeloma suggests that the modulation of individual ubiquitin-protein ligase activities with synthetic agents may represent a novel approach that has enormous potential for the treatment of a wide range of diseases [20].

Other interactions of UBE3AP2

• AS is caused by maternal deficiency of UBE3A (E6 associated protein ubiquitin protein ligase 3A gene), located in an imprinted region on chromosome 15q11-q13 [21].
• Re: Savtchenko et al. (1988): "Embryonic Expression of the Human 40-kD Keratin: Evidence from a Processed Pseudogene Sequence" [22].

References