Recombinant Human E3 ubiquitin-protein ligase RNF128 (RNF128), partial

Function

E3 ubiquitin-protein ligase that catalyzes 'Lys-27', 'Lys-48'- or 'Lys-63'-linked polyubiquitin chains formation and plays a role in different biological processes such as modulation of immune response, cytoskeletal dynamics or protein homeostasis. 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 (PubMed:12705856). Ubiquitinates ARPC5 with 'Lys-48' linkages and COR1A with 'Lys-63' linkages leading to their degradation, down-regulation of these cytoskeletal components results in impaired lamellipodium formation and reduced accumulation of F-actin at the immunological synapse (PubMed:22016387). Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals. Plays a positive role in innate immune response by promoting 'Lys-63'-linked ubiquitination of TBK1 after RNA- or DNA-virus infection (PubMed:27776110). Regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-kappa-B activation, hence decreasing pro-inflammatory cytokines (PubMed:37344492). Negatively regulates the IL-3/STAT5 signaling pathway by facilitating 'Lys-27'-linked polyubiquitination of IL3RA leading to its degradation via lysosomal pathway (PubMed:38702781). Directly regulates the N-glycosylation process in the endoplasmic reticulum by targeting the glycosyl-transferase RPN1 for ubiquitination and degradation (PubMed:39567208). Other substrates targeted for degradation by RNF128 include transmembrane proteins CD40L, CD83 or the tetraspanin CD151 (PubMed:18713730, PubMed:19542455)

Subcellular Location

Cytoplasm; Endomembrane system (Single-pass membrane protein); Cytoplasm, cytoskeleton; Cytoplasm, perinuclear region

Pathway

Protein modification; protein ubiquitination

• Anandasabapathy N. et al. GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4+ T cells. — Immunity (2003)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Ross M.T. et al. The DNA sequence of the human X chromosome. — Nature (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Lineberry N. et al. The single subunit transmembrane E3 ligase gene related to anergy in lymphocytes (GRAIL) captures and then ubiquitinates transmembrane proteins across the cell membrane. — J. Biol. Chem. (2008)
• Su L.L. et al. The transmembrane E3 ligase GRAIL ubiquitinates and degrades CD83 on CD4 T cells. — J. Immunol. (2009)
• Ichikawa D. et al. GRAIL (gene related to anergy in lymphocytes) regulates cytoskeletal reorganization through ubiquitination and degradation of Arp2/3 subunit 5 and coronin 1A. — J. Biol. Chem. (2011)
• Song G. et al. E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1. — Nat. Immunol. (2016)