Regulator of nonsense transcripts 3B (UPF3B)
The protein contains 483 amino acids for an estimated molecular weight of 57762 Da.
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. (updated: April 1, 2015)
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.
- 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.
- 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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| MRXS14 |
Biological Process
Gene expression
MRNA 3'-end processing
MRNA export from nucleus
MRNA splicing, via spliceosome
Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Positive regulation of translation
RNA export from nucleus
RNA splicing
Termination of RNA polymerase II transcription
Transcription by RNA polymerase II
The reference OMIM entry for this protein is 300298
Upf3, yeast, homolog of, b; upf3b
Regulator of nonsense transcripts 3b; rent3b
Upf3x
DESCRIPTION
Nonsense-mediated decay (NMD) is a mechanism for degrading transcripts with premature termination codons arising from errors in transcription or splicing, from mutated genes, or from genes that are physiologically regulated by NMD. UPF3A (605530) and UPF3B are components of an exon-junction complex that promotes NMD and regulates translation efficiency (summary by Kunz et al., 2006).CLONING
By searching sequence databases for homologs of the yeast Upf2 and Upf3 genes, followed by RT-PCR, Lykke-Andersen et al. (2000) isolated cDNAs encoding 3 human proteins, which they named UPF2 (605529), UPF3A, and UPF3B. The predicted UPF2, UPF3A, and UPF3B proteins contain 1,272, 476, and 470 amino acids, respectively. Using comparative genomics and RACE, Serin et al. (2001) isolated cDNAs encoding UPF3A, which they called UPF3, and UPF3B, which they called UPF3X. UPF3B encodes a 483-amino acid protein and a 470-amino acid splice variant that lacks exon 8. Northern blot analysis revealed expression of a 2.4-kb UPF3B transcript in HeLa cells. RT-PCR detected variable UPF3B expression in all tissues examined, with highest expression in testis and fetal brain. Epitope-tagged UPF3B was expressed in the nucleus of transfected HeLa cells.GENE FUNCTION
Using mutation and Western blot analyses, Serin et al. (2001) showed that the central-to-C-terminal portion of UPF2 interacted with the N-terminal nuclear export signal of UPF3B. Lykke-Andersen et al. (2000) found that UPF2, UPF3A, and UPF3B were complexed with UPF1 (RENT1; 601430) while in HeLa cell extracts. In intact cells, UPF3A and UPF3B were found to be nucleocytoplasmic shuttling proteins, while UPF2 was perinuclear, and UPF1 was cytoplasmic. UPF3A and UPF3B associated selectively with spliced beta-globin (141900) mRNA in vivo, and tethering of any UPF protein to the 3-prime untranslated region of beta-globin mRNA elicited NMD. These data suggested that assembly of a dynamic human UPF complex initiates in the nucleus at mRNA exon-exon junctions and triggers NMD in the cytoplasm when recognized downstream of a translation termination site. By immunoprecipitation and immunoblot analyses of nucleoplasmic fractions, Kim et al. (2001) showed that UPF3A and UPF3B are associated in an RNase-resistant manner with Y14 (RBM8A; 605313), as well as with the mRNA export factors ALY (604171) and TAP (NXF1; 602647), in mRNA-protein complexes. UPF3 proteins appeared to bind immediately upstream of exon-exon junctions. Kim et al. (2001) concluded that UPF3 proteins facilitate the export of spliced mRNAs by recruiting mRNA export proteins. They proposed that UPF3 functions in NMD and travels with the mRNA to the cytoplasm, where a leading translating ribosome displaces the UPF3-Y14 complexes from the mRNA. Using a reporter gene assay to quantify mRNA stability against NMD, Kunz et al. (2006) showed that UPF3B caused NMD, whereas both isoforms of UPF3A, UPF3AL and UPF3AS, had only weak NMD activity. Mutation analysis revealed that the C termini of UPF3A and UPF3B were largely responsible for NMD activity. The elevated NMD activity of UPF3B was due to the presence of arg419, which is lacking in UPF3A. Immunoprecipitation analysis revealed that NMD activity also required interaction of UPF3AL, UPF3AS, or UPF3B with Magoh (602603), but not with UPF2. All UPF3 isoforms that showed at least partial NMD activity coprecipitated with Magoh and also with EIF4AIII (EIF4A3; 608546) and ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300298 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed