Acts as a signaling pathway regulator involved in innate immune system response. 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. In complex with NMI, inhibits virus-triggered type I interferon/IFN-beta production. 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. 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. 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.

1. IFI35 enhances proliferation of mesangial cells and is regulated by MBD2 in lupus nephritis. PMID: 28064541
2. Damage-associated molecular patterns (DAMP) are important mediators of innate immunity. Here the authors show that N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs to promote inflammation by activating macrophages via the Toll-like receptor 4 and NF-kappaB pathways. PMID: 29038465
3. Study found that TLR3 signaling induces the expression of IFI35, and IFI35 negatively regulates IFN-beta-P-STAT1-RIG-I-CXCL10/CCL5 axis in U373MG cells. This suggests that IFI35 expressed in astrocytes may play an important role in regulating the innate immune system in astrocytoma cells. PMID: 28109979
4. Activation of TLR3 by poly IC induces the IFI35 expression in Mesangial Cells. Regional expression of IFI35 and its dysregulation may be involved in the pathogenesis of glomerular inflammation in CKD. PMID: 27639618
5. Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response PMID: 26342464
6. Knockdown of IFP35 expression abolished pEGFP-N1-2C and pEGFP-N1-Nmi-induced activation of type I interferon promoters. PMID: 25085622
7. IFI35 negatively regulates RIG-I antiviral signaling and supports vesicular stomatitis virus replication. PMID: 24371060
8. IRF-1 also activates IFP35 expression in an IFN-gamma-inducible manner. PMID: 23226549
9. Dissociation of the IFN-induced protein IFP35 from NMI is a newly defined specific cytoplasmic event occurring during apoptosis. PMID: 11911807
10. The results provide a novel role of CKIP-1 in cytokine signaling response and the biochemical mechanism, by which two previously identified modulators IFP35 and Nmi are involved via interactions. PMID: 17197158
11. IFP35 can interact with the bovine Tas (BTas) regulatory protein of bovine foamy virus; overexpression of IFP35 disturbs the ability of BTas to activate viral-gene transcription and inhibits viral replication. PMID: 18305040

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Cytoplasm. Nucleus. Secreted.

NMI family

Expressed in a wide range of cell types, including fibroblasts, macrophages, and epithelial cells.

HGNC: 5399

OMIM: 600735

KEGG: hsa:3430

STRING: 9606.ENSP00000395590

UniGene: Hs.632258