IFI35

IFI35 (Interferon Induced Protein 35) is a Protein Coding gene. Diseases associated with IFI35 include Stomatitis. Among its related pathways are Cytokine Signaling in Immune system and Innate Immune System. An important paralog of this gene is NMI.

Full Name

Interferon Induced Protein 35

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 proinflammatory cytokines (PubMed:29038465).

Biological Process

Innate immune response Source: UniProtKB-KW
Macrophage activation involved in immune response Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of NIK/NF-kappaB signaling Source: UniProtKB
Positive regulation of inflammatory response Source: UniProtKB
Positive regulation of innate immune response Source: UniProtKB
Positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
Positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKB

Cellular Location

Cytoplasm; Secreted; Nucleus. Cytoplasmic IFI35 localizes in punctate granular structures (PubMed:10950963). Nuclear localization increased is stimulated by IFN-alpha (PubMed:8288566, PubMed:10950963). Extracelullar following secretion by macrophage (PubMed:29038465).

PTM

Phosphorylated. Dephosphorylation correlates with the formation of a complex with NMI.