Interferon-induced 35 kDa protein (IFI35)
The protein contains 286 amino acids for an estimated molecular weight of 31546 Da.
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). (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs588703 | |
| dbSNP:rs588703 |
Biological Process
Cytokine-mediated signaling pathway
Macrophage activation involved in immune response
Negative regulation of cell population proliferation
Negative regulation of NIK/NF-kappaB signaling
Positive regulation of inflammatory response
Positive regulation of innate immune response
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of toll-like receptor 4 signaling pathway
Type I interferon signaling pathway
The reference OMIM entry for this protein is 600735
Interferon-induced protein 35; ifi35
Interferon-inducible protein, 35-kd; ifp35
CLONING
Interferons ( e.g., 147660) affect cellular functions by altering the expression of a number of specific genes. Bange et al. (1994) reported a human cDNA, designated IFP35 by them (interferon-inducible protein of 35 kD), which they cloned from interferon-gamma (147570)-induced HeLa cell mRNA screened by differential hybridization. The cDNA encodes a 282-amino acid predicted protein containing a leucine zipper motif at the amino terminus. Unlike most other leucine zipper proteins, IFP35 lacks a basic domain associated with DNA binding. Bange et al. (1994) found that in vitro translation of IFP35 mRNA resulted in the synthesis of a 35-kD protein. Northern blots showed that the 1.4-kb IFP35 mRNA occurs in fibroblasts, macrophages, and epithelial cells following interferon treatment. Western blots indicated that the IFP35 gene product can form homodimers and that there was increased nuclear localization following interferon treatment.MAPPING
Brown et al. (1995), as part of an effort to clone the BRCA1 gene (113705), used exon trapping to identify genes in a 500-kb region on 17q21. Among the exons identified from a phage P1 artificial chromosome (PAC) that included regions from BRCA1 were several coding regions with 100% identity to IFP35. Smith et al. (1996) likewise found the IFP35 gene situated centromeric to the BRCA1 gene in the course of sequencing and analyzing 117 kb of DNA from the 17q21 region. ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600735 was added.