IFI35
Domain
The NID domain 1 is involved in the negative regulation of p65/RELA transcription and the negative regulation of NF-kappa-B pathway activation.
Function
Acts as a signaling pathway regulator involved in innate immune system response (PubMed:26342464, PubMed:29038465, PubMed:29350881). In response to interferon IFN-alpha, associates in a complex with signaling pathway regulator NMI to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35 and correlates with IFI35 dephosphorylation (PubMed:10779520, PubMed:10950963). In complex with NMI, inhibits virus-triggered type I interferon/IFN-beta production (PubMed:26342464). In complex with NMI, negatively regulates nuclear factor NF-kappa-B signaling by inhibiting the nuclear translocation, activation and transcription of the NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial cell proliferation, migration and re-endothelialization of injured arteries (PubMed:29350881). Beside its role as an intracellular signaling pathway regulator, also functions extracellularly as damage-associated molecular patterns (DAMPs) to promote inflammation when actively released by macrophage to the extracellular space during cell injury and pathogen invasion (PubMed:29038465). Macrophage-secreted IFI35 activates NF-kappa-B signaling in adjacent macrophages through Toll-like receptor 4/TLR4 activation, thereby inducing NF-kappa-B translocation from the cytoplasm into the nucleus which promotes the release of pro-inflammatory cytokines (PubMed:29038465).
Post-translational modifications
Phosphorylated. Dephosphorylation correlates with the formation of a complex with NMI.
Sequence Similarities
Belongs to the NMI family.
Tissue Specificity
Expressed in a wide range of cell types, including fibroblasts, macrophages, and epithelial cells.
Cellular localization
- Cytoplasm
- Nucleus
- Secreted
- Cytoplasmic IFI35 localizes in punctate granular structures (PubMed:10950963). Nuclear localization increased is stimulated by IFN-alpha (PubMed:10950963, PubMed:8288566). Extracelullar following secretion by macrophage (PubMed:29038465).
Alternative names
IFP35, IFI35, Interferon-induced 35 kDa protein, IFP 35, Ifi-35