Poly(rC)-binding protein 2 (PCBP2)
The protein contains 365 amino acids for an estimated molecular weight of 38580 Da.
Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. Major cellular poly(rC)-binding protein. Binds also poly(rU). Negatively regulates cellular antiviral responses mediated by MAVS signaling (PubMed:19881509). It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation (PubMed:19881509).', '(Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12414943, PubMed:24371074). Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD (PubMed:12414943). (updated: Oct. 25, 2017)
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.
- 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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Biological Process
Defense response to virus
Gene expression
Innate immune response
IRES-dependent viral translational initiation
MRNA metabolic process
MRNA splicing, via spliceosome
Negative regulation of defense response to virus
Negative regulation of type I interferon production
Positive regulation of transcription by RNA polymerase II
Proteasome-mediated ubiquitin-dependent protein catabolic process
Regulation of gene expression
Regulation of RNA metabolic process
RNA metabolic process
RNA splicing
Viral RNA genome replication
The reference OMIM entry for this protein is 601210
Poly(rc)-binding protein 2; pcbp2
Heterogeneous nuclear ribonucleoprotein e2; hnrnpe2
Hnrpe2
DESCRIPTION
Heterogeneous nuclear riboprotein E2 is a poly(rC)-binding protein with translational regulatory functions (Ostareck-Lederer et al., 1998).CLONING
Leffers et al. (1995) described the cloning and characterization of 2 cDNAs for poly(rC)-binding proteins, called PCBP1 (601209) and PCBP2 by them. The authors analyzed an EST database for sequences that were predicted to encode a protein with K-homologous (KH) domains. The 60- to 70-amino acid KH motifs are found in several putative nucleic acid binding proteins such as FMR1 (309550) and HNRNPK (600712) and are thought to be involved in RNA binding. Using primers from 1 EST the authors produced a probe that was used to screen a cDNA library of transformed human amnion cells. The cDNA they isolated for PCBP1 encodes a putative 356-amino acid protein that contains 3 KH domains. It is 83% identical to PCBP2 at the DNA level and 90% homologous at the amino acid level. The PCBP2 protein is about 99% similar to the mouse hnRNP-X/mCTBP protein (Hahm et al., 1993) and is a probable homolog. Chkheidze and Liebhaber (2003) determined that endogenous HeLa cell PCBP2 localized to the nucleus in a particulate and diffuse staining pattern that differed from the speckled pattern observed with PCBP1. They identified 2 nuclear localization signals within PCBP2, within a 9-amino acid segment between KH2 and KH3, and within a 12-amino acid segment of KH3. Mutation analysis revealed that both signals were required for nuclear localization. A splice variant of PCBP2 that contains a 31-amino acid segment between KH2 and KH3 showed both nuclear and cytoplasmic distribution.GENE FUNCTION
When expressed with a vaccinia virus system in transformed amnion cells, Leffers et al. (1995) found that both PCBP1 and PCBP2 bound poly(rC) when not phosphorylated; phosphorylated protein bound with much lower affinity. Transcripts of both PCBPs were detected in all the human tissues analyzed. Studying the arrest of differentiation, which is a feature of chronic myelogenous leukemia cells with the fusion BCR-ABL gene (151410), Perrotti et al. (2002) found that BCR-ABL regulates the expression of C/EBP-alpha (CEBPA; 116897), the principal regulator of granulocytic differentiation, inducing HNRNPE2, which inhibits the translation of CEBPA mRNA. Using mouse and human myelogenous leukemia cell lines, Eiring et al. (2010) showed that microRNA-328 (MIR328; 613701) inhibited HNRNPE2 activity. A C-rich region of the mature MIR328 sequence interacted with the poly(rC)-binding region HNRNPE2. This interaction prevented binding between HNRNPE2 and a C-rich 5-prime upstream region of CEBPA, releasing CEBPA from translational inhibition by HNRNPE2. Mir328 with a mutated seed sequence bound Hnrnpe2 and restored Cebpa expression in mouse myeloid precursors, indicating that the effects of MIR328 on HNRNPE2 and CEBPA were independent of its seed sequence.EVOLUTION
One of the most evolutionarily constrained regions in mammalian genomes is the ultraconserved element uc.338, a mammal-specific 223-basepair region perfectly conserved between human, mouse, and rat, overlapping a short protein-coding exon of PCBP2. Bejerano et al. (2006) showed that a class of conserved primarily noncoding regions in tetrapods originated from a previously unknown short interspersed repetitive element (SINE) retroposon family that was active in the Sarcopterygii (lobe-finned fishes and terrestrial vertebrates) in ... More on the omim web site
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for PCBP2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601210 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed