Disease relevance of UbcD4

• Recently, loss-of-function mutations in the parkin gene, which encodes a ubiquitin-protein ligase, were found to underlie a familial form of PD known as autosomal recessive juvenile parkinsonism (AR-JP) [1].
• Bruce is a large protein (530 kDa) that contains an N-terminal baculovirus IAP repeat (BIR) and a C-terminal ubiquitin conjugation domain (E2) [2].

High impact information on UbcD4

• The c-Cbl proto-oncogene is a RING family E3 that recognizes activated receptor tyrosine kinases, promotes their ubiquitination by a ubiquitin-conjugating enzyme (E2) and terminates signaling [3].
• Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning [4].
• Thus, in addition to uncovering E2/E3 ubiquitinating enzymes for dendrite pruning, this study provides a mechanistic link between UPS and the apoptotic machinery in regulating neuronal process remodeling [4].
• Moreover, in females doubly mutant for bam and the ubiquitin protein ligase Smurf, the number of germ cells responsive to Dpp is greatly increased relative to the number observed in either single mutant [5].
• This study demonstrates that an E2 enzyme is required for nuclear transport during Drosophila embryogenesis [6].

Anatomical context of UbcD4

• Here, we report the purification and characterization of a novel 18-kDa species of E2 from rabbit reticulocytes [7].
• In vitro studies with vertebrate proteins demonstrate that the RanGAP1 associated with the nuclear pore complex is modified with small ubiquitin related modifier-1 (SUMO-1) by a ubiquitin-conjugating enzyme (E2 enzyme) [9-15] [6].
• In transgenic animals, the E1 and E2 clusters are functionally connected, and both elements are required for NK-4 activation in cells of the visceral mesoderm and also for NK-4 repression in cells of the somatic musculature [8].

Associations of UbcD4 with chemical compounds

• Unlike most members of the E2 family, this enzyme does not adsorb to anion exchange resin in neutral pH, and it is purified from the unadsorbed material (Fraction 1) [7].

Physical interactions of UbcD4

• UbcD4 can interact with the polyubiquitin-binding subunit of the proteasome [9].

References