E3 ubiquitin-protein ligase RNF128
Domain
Binding to E2 ubiquitin-conjugating enzyme requires an intact RING finger domain.
Function
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.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Auto-ubiquitinated. Controls the development of T-cell clonal anergy by ubiquitination.
Cellular localization
- Endomembrane system
- Single-pass membrane protein
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Perinuclear region
- 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 (By similarity).
Alternative names
E3 ubiquitin-protein ligase RNF128, Gene related to anergy in lymphocytes protein, RING finger protein 128, RING-type E3 ubiquitin transferase RNF128, GRAIL, RNF128