E3 ubiquitin-protein ligase that catalyzes 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains formation. Functions as an inhibitor of cytokine gene transcription. Inhibits IL2 and IL4 transcription, thereby playing an important role in the induction of the anergic phenotype, a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of interleukin production. Ubiquitinates ARPC5 with 'Lys-48' linkages and COR1A with 'Lys-63' linkages leading to their degradation, down-regulation of these cytosleletal components results in impaired lamellipodium formation and reduced accumulation of F-actin at the immunological synapse. Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Localized in an asymmetric perinuclear punctate manner. Localizes to the internal pool of the transferrin recycling endosomal pathway. Partially colocalized with the endoplasmic reticulum resident HSPA5, with Golgi resident STX5, and with the late endosomal GTPase RAB7A. Expressed in brain, kidney, heart, liver, ovary, testis and thymus. Expression increased as early as 4 hours by 5- to 7-fold in anergized cultures as compared to resting or activated cells. At 6.0 dpc, expressed in both the extraembryonic endoderm and extraembryonic ectoderm. After the beginning of gastrulation, expression remains extraembryonic, and is mostly confined to the visceral endoderm. At 8.5 dpc, expression appears within the mesodermally derived allantois, and is highly expressed in the epithelial layer of the yolk sac. At 9.5 dpc, expressed in the hindgut and adjoining yolk sac. At stage 10 dpc, appears to be widely expressed throughout the embryo with higher expression within the branchial arches and within intersomitic endothelial cells. Induced under anergic conditions. Up-regulated during T-cell anergy induction following signaling through the T-cell antigen receptor. Binding to E2 ubiquitin-conjugating enzyme requires an intact RING finger domain. Auto-ubiquitinated. Controls the development of T-cell clonal anergy by ubiquitination.