Interleukin enhancer-binding factor 3 (ILF3)
The protein contains 894 amino acids for an estimated molecular weight of 95338 Da.
RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs (PubMed:28625552). As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response (PubMed:21123651). Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs (PubMed:21123651, PubMed:28625552). (updated: Nov. 7, 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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:rs1064493 | |
| dbSNP:rs34520379 |
Biological Process
Defense response to virus
Negative regulation of transcription, DNA-templated
Negative regulation of translation
Negative regulation of viral genome replication
Positive regulation of transcription, DNA-templated
Protein phosphorylation
Transcription, DNA-templated
The reference OMIM entry for this protein is 603182
Interleukin enhancer-binding factor 3; ilf3
Nuclear factor of activated t cells, 90-kd; nf90
Double-stranded rna-binding protein, 76-kd; drbp76
M-phase phosphoprotein 4; mpp4; mphosph4
Nuclear factor associated with double-stranded rna; nfar
For background information, see NF45 (ILF2; 603181).
CLONING
Kao et al. (1994) cloned cDNAs encoding NF45 and NF90. The NF90 gene encodes a 671-amino acid polypeptide with limited similarity to several RNA-binding proteins. The NF90 gene also appears to encode an alternatively spliced 404-amino acid polypeptide, of which the first 394 amino acids are identical to the longer clone. Northern and Western blot analysis demonstrated NF45 and NF90 expression in several cell types, including both unstimulated and stimulated Jurkat T cells. By immunoscreening a HeLa cell cDNA library for phosphoproteins, Matsumoto-Taniura et al. (1996) isolated a partial cDNA encoding ILF3, which they termed MPP4. Immunoprecipitation analysis indicated that MPP4 encodes 90- and 110-kD proteins. Immunofluorescence microscopy demonstrated cytoplasmic expression during M phase and nuclear/nucleolar expression during interphase. Patel et al. (1999) purified double-stranded RNA (dsRNA)-binding proteins from HeLa cell extracts and microsequenced a 90-kD protein with identity to MPP4 in its N terminus. Using a yeast 2-hybrid screen with a mutant RNA-activated protein kinase (PRKR; 176871) as bait, followed by RT-PCR, they isolated a full-length cDNA encoding ILF3, which they called DRBP76. Sequence analysis predicted that the 702-amino acid protein has a bipartite nuclear localization signal, 2 dsRNA-binding domains, an RG2 domain, and multiple potential phosphorylation sites. SDS-PAGE analysis showed expression of a 90-kD protein, larger than the calculated 76 kD. EMSA analysis confirmed the dsRNA binding activity of DRBP76. Autoradiographic analysis indicated that DRBP76 is phosphorylated by PRKR. Langland et al. (1999) noted that NF90 is primarily localized to ribosomes. Saunders et al. (2001) obtained a cDNA encoding DRBP76, which they termed NFAR1, as well as a variant cDNA encoding a 110-kD, 894-amino acid protein they designated NFAR2. Sequence analysis showed that the NFAR proteins share homology with a known PRKR substrate, the translation initiation factor EIF2S1 (603907). Northern blot analysis revealed ubiquitous expression of multiple transcripts ranging from 4.0 to 8.0 kb. Immunoblot analysis indicated variable expression with lower amounts particularly notable in liver and spleen, suggesting differential regulation at the translational or posttranslational level. Immunoblot analysis and confocal microscopy demonstrated that PRKR and both NFAR variants reciprocally coimmunoprecipitate and colocalize in the nucleus. Immunoprecipitation analysis indicated an association with spliceosomes. Viranaicken et al. (2006) identified splice variants of human and mouse ILF3 that encode long and short isoforms of the ILF3 and NF90 proteins via inclusion or exclusion of 13 N-terminal residues, respectively.GENE FUNCTION
Kao et al. (1994) showed that the NF45 and NF90 proteins form an NFAT DNA-binding activity that is enhanced by T-cell stimulation and inhibited by cyclosporin A and FK506. Functional analysis by Saunders et al. (2001) indicated that both NFAR proteins regulate gene transcription, probably at the level of mRNA elongation. NFAR2 exhibited potent, constitutive regulatory activity through its unique C-terminal region, which specifically interacted with FUS (137070) and SMN1 (600354). Saunders et al. (2001) concluded that NFARs facilitate dsRNA-regulated gene expression at the level of posttranscription. Shim et al. (2002) showed that ... More on the omim web site
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: 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 603182 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed