Interferon-induced protein with tetratricopeptide repeats 5 (IFIT5)
The protein contains 482 amino acids for an estimated molecular weight of 55847 Da.
Interferon-induced RNA-binding protein involved in the human innate immune response. Has a broad and adaptable RNA structure recognition important for RNA recognition specificity in antiviral defense. Binds precursor and processed tRNAs as well as poly-U-tailed tRNA fragments (PubMed:25092312, PubMed:23317505, PubMed:23774268). Specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA), thereby acting as a sensor of viral single-stranded RNAs. Single-stranded PPP-RNAs, which lack 2'-O-methylation of the 5' cap and bear a 5'-triphosphate group instead, are specific from viruses, providing a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Directly binds PPP-RNA in a non-sequence-specific manner (PubMed:23334420). Also recognizes and selectively binds AT-rich dsDNA (PubMed:23774268). Additionally, as a mediator in innate immunity, regulates positively IKK-NFKB signaling by sinergizing the recruitment of IKK to MAP3K7 (PubMed:26334375). (updated: Jan. 31, 2018)
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.
- 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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Defense response to virus
Innate immune response
Negative regulation of viral genome replication
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Type I interferon signaling pathway
The reference OMIM entry for this protein is 616135
Interferon-induced protein with tetratricopeptide repeats 5; ifit5
Retinoic acid- and interferon-induced protein, 58-kd; ri58
Interferon-stimulated protein, 58-kd; isg58
DESCRIPTION
Interferon (IFN)-induced proteins with tetratricopeptide repeats (TPRs), or IFITs, accumulate following type I IFN (see IFNA, 147660) signaling. IFIT5 is an RNA-binding protein with an adaptable RNA-binding site that can accommodate and distinguish phosphate-containing 5-prime ends. It is important for innate immunity (Katibah et al., 2014).CLONING
Using differential hybridization of retinoic acid-treated human NB4 granulocytic cells, followed by 5-prime RACE, Niikura et al. (1997) isolated a cDNA encoding IFIT5, which they called RI58. The predicted 482-amino acid protein shares 55% identity with IFIT1 (147690). It contains 14 putative TPRs, each composed of 34-amino acid repeats that include 8 hydrophobic residues that contribute to the snap helix. Northern blot analysis of NB4 cells revealed 4.1-, 2.8-, and 1.6-kb transcripts. Western blot analysis showed expression of a 58-kD protein.BIOCHEMICAL FEATURES
Abbas et al. (2013) reported the crystal structures of full-length IFIT5, an N-terminal fragment of IFIT1, and a complex of IFIT5 with a 5-prime-triphosphate RNA (PPP-RNA), a molecular signature that distinguishes viral from host RNA. The structures revealed a helical domain that housed a positively charged cavity designed to specifically engage only single-stranded PPP-RNA, thus distinguishing it from RIGI (DDX58; 609631), which recognizes double-stranded viral PPP-RNA. Feng et al. (2013) obtained the 2.1-angstrom crystal structure of IFIT5, which showed 24 alpha helices packed into a special V-like structure. Helices 3 through 24 were assembled into 11 tandem TPR motifs. The authors noted that the N terminus of IFIT5 is conserved among other IFIT members.GENE FUNCTION
Niikura et al. (1997) found that expression of RI58 in NB4 cells was induced by IFNA and IFNB (147640), with weaker induction by IFNG (147570). Retinoic acid induced expression of IFNA, which in turn induced IFIT5 expression. IFNA-dependent expression was also seen in other immune cell lines, whereas IFNA-independent, constitutive expression was found in HeLa and other cancer cell lines. Katibah et al. (2013) reported that IFIT5, unlike other TPR proteins, did not pack bihelical repeats to create a platform for protein-protein interactions. Instead, a monomer of IFIT5 bound directly, specifically, and autonomously to endogenous cellular RNA with 5-prime ends, including transfer RNAs (tRNAs). RNA recognition required a convoluted intramolecular fold of the IFIT5 TPRs, forming an RNA-binding cleft. IFIT1 and RIGI colocalized in actin-rich structures at the apical cell surface, suggesting compartmentalization in the cell periphery where innate immune-response proteins interact with RNA ligands. By mutational analysis and gel-shift assays, Abbas et al. (2013) found that PPP-RNA bound to IFIT5 in a non-nucleotide sequence-specific manner and required a 5-prime overhang of approximately 3 nucleotides. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 resulted in a defective antiviral response. Using EMSA, Feng et al. (2013) determined that IFIT5 bound poly(A) and poly(U) single-stranded RNA (ssRNA) with high affinity. IFIT5 bound relatively poorly to ssDNA, yet selectively bound to AT-rich double-stranded DNA (dsDNA), a feature distinct from other IFIT proteins. IFIT5 inhibited replication of vesicular stomatitis virus (VSV), and this inhibition was impaired with IFIT5 containing lys415-to-glu (K415E) and arg384-to- ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616135 was added.
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for IFIT5
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed