HGNC Approved Gene Symbol: PCBP1
Cytogenetic location: 2p13.3 Genomic coordinates (GRCh38): 2:70,087,477-70,089,203 (from NCBI)
Leffers et al. (1995) described the cloning and characterization of 2 cDNAs for poly(rC)-binding proteins, called PCBP1 and PCBP2 (601210) 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 PCBP1 protein is about 85% similar to the mouse hnRNP-X/mCTBP protein (Hahm et al., 1993).
Chkheidze and Liebhaber (2003) determined that endogenous HeLa cell PCBP1 colocalized to nuclear speckles with SC35 (600813). They identified a nuclear localization signal within a 9-amino acid segment between KH2 and KH3. Deletion of this segment blocked nuclear accumulation of PCBP1.
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.
By yeast 2-hybrid analysis of a human brain cDNA library, Kosturko et al. (2006) found that mouse Hnrnpa2 (600124) interacted with human HNRNPE1. They confirmed the interaction with in vivo and in vitro protein interaction assays. Hnrnpe1 colocalized with Hnrnpa2 and A2RE mRNA in granules in dendrites of rat oligodendrocytes. Overexpression of HNRNPE1 or microinjection of exogenous HNRNPE1 in rat neural cells inhibited translation of A2RE mRNA, but not translation of mutated A2RE mRNA. Excess HNRNPE1 added to an in vitro translation system reduced translation efficiency of A2RE mRNA in an Hnrnpa2-dependent manner. Kosturko et al. (2006) hypothesized that binding of HNRNPE1 to HNRNPA2 inhibits A2RE mRNA translation during granule transport.
Shi et al. (2008) identified PCBP1 in a genetic screen to identify human genes that, when expressed in yeast, could increase the amount of iron loaded into ferritin (see 134790). PCBP1 bound to ferritin in vivo, and bound iron and facilitated iron loading into ferritin in vitro. Depletion of PCBP1 in human cells inhibited ferritin iron loading and increased cytosolic iron pools. Thus, Shi et al. (2008) concluded that PCBP1 can function as a cytosolic iron chaperone in the delivery of iron to ferritin.
Transcripts of both PCBPs were detected in all the human tissues analyzed. Tommerup and Leffers (1996) mapped PCBP1 to 2p13-p12 by fluorescence in situ hybridization.
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]
Hahm, K., Kim, G., Turck, C. W., 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]
Kosturko, L. D., Maggipinto, M. J., Korza, G., Lee, J. W., Carson, J. H., Barbarese, E. Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs. Molec. Biol. Cell 17: 3521-3533, 2006. [PubMed: 16775011] [Full Text: https://doi.org/10.1091/mbc.e05-10-0946]
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]
Shi, H., Bencze, K. Z., Stemmler, T. L., Philpott, C. C. A cytosolic iron chaperone that delivers iron to ferritin. Science 320: 1207-1210, 2008. [PubMed: 18511687] [Full Text: https://doi.org/10.1126/science.1157643]
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]