RNF128

The protein encoded by this gene is a type I transmembrane protein that localizes to the endocytic pathway. This protein contains a RING zinc-finger motif and has been shown to possess E3 ubiquitin ligase activity. Expression of this gene in retrovirally transduced T cell hybridoma significantly inhibits activation-induced IL2 and IL4 cytokine production. Induced expression of this gene was observed in anergic CD4(+) T cells, which suggested a role in the induction of anergic phenotype. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Full Name

Ring Finger Protein 128, E3 Ubiquitin Protein Ligase

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.

Biological Process

Biological Process negative regulation of cytokine productionIEA:Ensembl
Biological Process positive regulation of protein catabolic process in the vacuole1 PublicationIC:BHF-UCL
Biological Process protein localization to lysosome1 PublicationIC:BHF-UCL
Biological Process regulation of protein stabilityManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Endomembrane system
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).

Topology

Helical: 208-228

PTM

Auto-ubiquitinated. Controls the development of T-cell clonal anergy by ubiquitination.