TRIM8
Domain
The coiled coil domain is required for homodimerization.
The region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.
Function
E3 ubiquitin-protein ligase that participates in multiple biological processes including cell survival, differentiation, apoptosis, and in particular, the innate immune response (PubMed:27981609, PubMed:28747347). Participates in the activation of interferon-gamma signaling by promoting proteasomal degradation of the repressor SOCS1 (PubMed:12163497). Plays a positive role in the TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the 'Lys-63'-linked polyubiquitination of MAP3K7/TAK1 component leading to the activation of NF-kappa-B (PubMed:22084099, PubMed:23152791, PubMed:27981609, PubMed:34871740). Modulates also STAT3 activity through negative regulation of PIAS3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus (PubMed:20516148). Negatively regulates TLR3/4-mediated innate immune response by catalyzing 'Lys-6'- and 'Lys-33'-linked polyubiquitination of TICAM1 and thereby disrupting the TICAM1-TBK1 interaction (PubMed:28747347).
Involvement in disease
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
FSGSNEDS
An autosomal dominant disorder characterized by global developmental delay associated with variable features of focal segmental glomerulosclerosis, a renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Some patients have transient proteinuria and others require renal transplant. Neurodevelopmental features are also variable, with some patients having only mildly impaired intellectual development, and others having a severe developmental disorder associated with early-onset refractory seizures or epileptic encephalopathy. Additional features, including feeding difficulties, poor overall growth, and non-specific dysmorphic facial features, are commonly observed.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein ubiquitination.
Sequence Similarities
Belongs to the TRIM/RBCC family.
Tissue Specificity
Widely expressed. Expressed in glomerular podocytes of kidneys.
Cellular localization
- Cytoplasm
- Nucleus
- Nucleus
- Nuclear body
- Nucleo-cytoplasmic translocation is involved in regulation of NF-kappa-B.
Alternative names
GERP, RNF27, TRIM8, E3 ubiquitin-protein ligase TRIM8, Glioblastoma-expressed RING finger protein, RING finger protein 27, RING-type E3 ubiquitin transferase TRIM8, Tripartite motif-containing protein 8