Alternative titles; symbols
HGNC Approved Gene Symbol: PCBP2
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:53,452,102-53,481,162 (from NCBI)
Heterogeneous nuclear riboprotein E2 is a poly(rC)-binding protein with translational regulatory functions (Ostareck-Lederer et al., 1998).
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.
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.
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 the Silurian period at least 410 million years ago, and seems to be recently active in the 'living fossil' Indonesian coelacanth, Latimeria menadoensis. Using a mouse enhancer assay, Bejerano et al. (2006) showed that one copy, 0.5 million bases from the neurodevelopmental gene ISL1 (600366), is an enhancer that recapitulates multiple aspects of Isl1 expression patterns. Several other copies represent new, possibly regulatory, alternatively spliced exons in the middle of preexisting Sarcopterygian genes. One of these, a more than 200-basepair ultraconserved region, 100% identical in mammals, and 80% identical to the coelacanth SINE, contains a 31-amino-acid residue alternatively spliced exon of the mRNA processing gene PCBP2. Bejerano et al. (2006) concluded that this SINE element adds to a growing list of examples in which relics of transposable elements have acquired a function that serves their host, a process termed 'exaptation', and provide an origin for at least some of the many highly conserved vertebrate-specific genomic sequences.
Tommerup and Leffers (1996) mapped PCBP2 distal to FRA12A (136630) at 12q13.12-q13.13 by fluorescence in situ hybridization.
Makeyev and Liebhaber (2000) identified 2 processed PCBP2 pseudogenes that mapped to chromosome 21q22.3 and chromosome 8q21-q22.
Makeyev and Liebhaber (2000) determined that the human and mouse PCBP2 genes contain 15 exons and span more than 19 kb.
Bejerano, G., Lowe, C. B., Ahituv, N., King, B., Siepel, A., Salama, S. R., Rubin, E. M., Kent, W. J., Haussler, D. A distal enhancer and an ultraconserved exon are derived from a novel retroposon. Nature 441: 87-90, 2006. [PubMed: 16625209] [Full Text: https://doi.org/10.1038/nature04696]
Chkheidze, A. N., Liebhaber, S. A. A novel set of nuclear localization signals determine distributions of the alpha-CP RNA-binding proteins. Molec. Cell. Biol. 23: 8405-8415, 2003. [PubMed: 14612387] [Full Text: https://doi.org/10.1128/MCB.23.23.8405-8415.2003]
Eiring, A. M., Harb, J. G., Neviani, P., Garton, C., Oaks, J. J., Spizzo, R., Liu, S., Schwind, S., Santhanam, R., Hickey, C. J., Becker, H., Chandler, J. C., and 13 others. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 140: 652-665, 2010. [PubMed: 20211135] [Full Text: https://doi.org/10.1016/j.cell.2010.01.007]
Hahm, K., Kim, G., Turck, C., Smale, S. T. Isolation of a murine gene encoding a nucleic acid-binding protein with homology to hnRNP K. Nucleic Acids Res. 21: 3894 only, 1993. [PubMed: 8367306] [Full Text: https://doi.org/10.1093/nar/21.16.3894]
Leffers, H., Dejgaard, K., Celis, J. E. Characterisation of two major cellular poly(rC)-binding human proteins, each containing three K-homologous (KH) domains. Europ. J. Biochem. 230: 447-453, 1995. [PubMed: 7607214]
Makeyev, A. V., Liebhaber, S. A. Identification of two novel mammalian genes establishes a subfamily of KH-domain RNA-binding proteins. Genomics 67: 301-316, 2000. [PubMed: 10936052] [Full Text: https://doi.org/10.1006/geno.2000.6244]
Ostareck-Lederer, A., Ostareck, D. H., Hentze, M. W. Cytoplasmic regulatory functions of the KH-domain proteins hnRNPs K and E1/E2. Trends Biochem. Sci. 23: 409-411, 1998. [PubMed: 9852755] [Full Text: https://doi.org/10.1016/s0968-0004(98)01301-2]
Perrotti, D., Cesi, V., Trotta, R., Guerzoni, C., Santilli, G., Campbell, K., Iervolino, A., Condorelli, F., Gambacorti-Passerini, C., Caligiuri, M. A., Calabretta, B. BCR-ABL suppresses C/EBP-alpha expression through inhibitory action of hnRNP E2. Nature Genet. 30: 48-58, 2002. [PubMed: 11753385] [Full Text: https://doi.org/10.1038/ng791]
Tommerup, N., Leffers, H. Assignment of human KH-box-containing genes by in situ hybridization: HNRNPK maps to 9q21.32-q21.33, PCBP1 to 2p12-p13, and PCBP2 to 12q13.12-q13.13, distal to FRA12A. Genomics 32: 297-298, 1996. [PubMed: 8833161] [Full Text: https://doi.org/10.1006/geno.1996.0121]