TRIM8

TRIM8 is a member of the tripartite motif (TRIM) protein family. Based on similarities to other proteins, TRIM8 is suspected to be an E3 ubiquitin-protein ligase. Regulation of this gene may be altered in some cancers. Mutations resulting in a truncated protein product have been observed in early-onset epileptic encephalopathy (EOEE).

Full Name

Tripartite Motif Containing 8

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).
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).

Biological Process

Biological Process innate immune response Source:UniProtKB1 Publication
Biological Process negative regulation of viral entry into host cell Source:Ensembl
Biological Process negative regulation of viral transcription Source:Ensembl
Biological Process positive regulation of autophagy Source:UniProtKB1 Publication
Biological Process positive regulation of DNA-binding transcription factor activity Source:UniProtKB1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signaling Source:UniProtKB1 Publication
Biological Process positive regulation of NF-kappaB transcription factor activity Source:UniProtKB1 Publication
Biological Process positive regulation of protein localization to nucleus Source:Ensembl
Biological Process protein ubiquitination Source:UniProtKB-UniPathway
Biological Process stem cell population maintenance Source:Ensembl
Biological Process suppression of viral release by host Source:UniProtKB1 Publication

Cellular Location

Cytoplasm
Nucleus
Nucleus, nuclear body
Nucleo-cytoplasmic translocation is involved in regulation of NF-kappa-B.

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.