PCBP1: Poly(rC) Binding Protein 1 – A Multifaceted RNA Chaperone in Gene Regulation and Disease
Comprehensive biomedical overview of PCBP1, including genomic annotation, expression, mutations, and clinical relevance.
Gene Information Card
| Symbol | PCBP1 |
|---|---|
| Full Name | Poly(rC) Binding Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p13.3 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000169564 |
| UniProt ID | Q15365 |
| OMIM ID | 601074 |
| HGNC ID | 8647 |
| Aliases | HNRNP-E1, HNRPE1, hnRNP E1, alpha-CP1 |
Description
PCBP1 (poly(rC) binding protein 1) encodes a member of the KH-domain containing RNA-binding protein family. It binds to polycytosine (poly(rC)) sequences in RNA and DNA, regulating mRNA stability, translation, and splicing. PCBP1 is involved in iron metabolism via interaction with iron-responsive elements (IREs), erythropoiesis, and viral RNA replication. It also functions as a transcriptional co-regulator and is implicated in cancer, thalassemia, and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alpha-thalassemia | PCBP1 mutations disrupt mRNA splicing of alpha-globin, leading to reduced hemoglobin production. | ClinVar; OMIM #601074 |
| Hereditary persistence of fetal hemoglobin (HPFH) | Altered PCBP1 binding to gamma-globin mRNA affects translation and HbF levels. | OMIM; PubMed studies |
| Hepatocellular carcinoma | PCBP1 downregulation promotes EMT and metastasis via post-transcriptional regulation of EMT-related mRNAs. | COSMIC; PubMed |
| Breast cancer | PCBP1 overexpression correlates with poor prognosis; regulates CD44 alternative splicing. | COSMIC; PubMed |
| Osteosarcoma | PCBP1 loss enhances tumor growth and invasion through modulation of c-Myc and p27. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Liver | 10.2 | Medium |
| Brain | 8.9 | Medium |
| Heart | 7.3 | Low |
| Lung | 9.1 | Medium |
| Kidney | 8.4 | Medium |
| Spleen | 11.0 | Medium |
| Testis | 13.8 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney; high expression |
| HeLa | 12.8 | Cervical carcinoma; moderate-high |
| HepG2 | 11.5 | Hepatocellular carcinoma; moderate |
| K562 | 15.1 | Chronic myeloid leukemia; very high |
| MCF7 | 10.3 | Breast cancer; moderate |
| A549 | 9.7 | Lung cancer; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; predicted loss of function |
| c.163C>T (p.Arg55Cys) | Missense | <0.01% | Altered RNA binding affinity |
| c.434G>A (p.Arg145His) | Missense | <0.01% | Reduced stability; associated with alpha-thalassemia |
| c.587_588del (p.Glu196fs) | Frameshift | <0.01% | Truncation; loss of KH domains |
| c.739C>T (p.Arg247Trp) | Missense | <0.01% | Impaired nuclear localization |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Glu196fs) lead to truncated protein lacking functional KH domains, reducing RNA binding and regulatory capacity.
Gain of Function (GOF)
Not well documented; some missense variants (e.g., p.Arg55Cys) may alter RNA target specificity, potentially acting as gain-of-function in certain contexts.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., p.Arg145His) can interfere with wild-type PCBP1 function in RNA processing, consistent with dominant-negative effects in alpha-thalassemia.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Iron metabolism and erythropoiesis (IRE/IRP system)
• mRNA splicing – minor spliceosome pathway
• Regulation of EMT and metastasis (TGF-beta signaling)
• Viral mRNA translation (e.g.
• poliovirus
• HCV)
• p53 signaling pathway (via MDM2 regulation)
Protein Summary
PCBP1 is a 356-amino acid protein containing three KH domains that mediate binding to poly(rC) sequences. It shuttles between nucleus and cytoplasm, participating in pre-mRNA splicing, mRNA stabilization, and translational control. PCBP1 is essential for iron homeostasis by binding to IREs in ferritin and transferrin receptor mRNAs. It also regulates alternative splicing of CD44 and other cancer-related genes. Post-translational modifications include phosphorylation and sumoylation, which modulate its subcellular localization and activity.
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