Details for: PCBP4

Gene ID: 57060

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PCBP4

Ensembl ID: ENSG00000090097

Description: poly(rC) binding protein 4

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • OFF-bipolar cell CL0000750
    CSI 26.37
    rCSI 36.06%
    PRS 89.43
  • ON-bipolar cell CL0000749
    CSI 21.85
    rCSI 32.47%
    PRS 89.64
  • retinal cone cell CL0000573
    CSI 21.13
    rCSI 34.02%
    PRS 83.14
  • peripheral nervous system neuron CL2000032
    CSI 17.84
    rCSI 24.31%
    PRS 84.59
  • epithelial cell CL0000066
    CSI 10.18
    rCSI 15.65%
    PRS 79.32
  • S cone cell CL0003050
    CSI 8.55
    rCSI 37.58%
    PRS 86.09
  • bronchus fibroblast of lung CL2000093
    CSI 7.15
    rCSI 5.81%
    PRS 90.08
  • interstitial cell of Cajal CL0002088
    CSI 6.9
    rCSI 8.78%
    PRS 94.02
  • progenitor cell CL0011026
    CSI 6.82
    rCSI 14.51%
    PRS 85.04
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 6.71
    rCSI 11.85%
    PRS 77.44
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 6.56
    rCSI 8.43%
    PRS 87.19
  • myoepithelial cell CL0000185
    CSI 5.83
    rCSI 14.76%
    PRS 93.04
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 5.5
    rCSI 10%
    PRS 84.52
  • interneuron CL0000099
    CSI 5.28
    rCSI 10.6%
    PRS 84.69
  • retinal rod cell CL0000604
    CSI 5.14
    rCSI 9.07%
    PRS 86.79
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 4.9
    rCSI 5.65%
    PRS 83.58
  • neuroplacodal cell CL0000032
    CSI 4.43
    rCSI 40.96%
    PRS 88.18
  • neural crest cell CL0011012
    CSI 4.42
    rCSI 3.49%
    PRS 83.94
  • rod bipolar cell CL0000751
    CSI 3.98
    rCSI 7.15%
    PRS 85.88
  • enteroendocrine cell CL0000164
    CSI 3.82
    rCSI 5.22%
    PRS 89.26
  • radial glial cell CL0000681
    CSI 3.82
    rCSI 5.31%
    PRS 89.25
  • eye photoreceptor cell CL0000287
    CSI 3.78
    rCSI 42.53%
    PRS 92.78
  • mature astrocyte CL0002627
    CSI 3.67
    rCSI 15.58%
    PRS 83.92
  • cerebellar granule cell CL0001031
    CSI 3.63
    rCSI 5.34%
    PRS 85.75
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.5
    rCSI 5.62%
    PRS 78.98
  • retinal bipolar neuron CL0000748
    CSI 3.35
    rCSI 6.28%
    PRS 82.56
  • stem cell CL0000034
    CSI 3.26
    rCSI 3.14%
    PRS 86.76
  • mesenchymal cell CL0008019
    CSI 3.05
    rCSI 7.74%
    PRS 85.77
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.05
    rCSI 3.79%
    PRS 75.87
  • skin fibroblast CL0002620
    CSI 2.88
    rCSI 2.48%
    PRS 90.33
  • retinal pigment epithelial cell CL0002586
    CSI 2.82
    rCSI 5.61%
    PRS 87.36
  • mesodermal cell CL0000222
    CSI 2.73
    rCSI 3.28%
    PRS 89.56
  • basal cell CL0000646
    CSI 2.7
    rCSI 3.61%
    PRS 88.21
  • GABAergic neuron CL0000617
    CSI 2.62
    rCSI 8.76%
    PRS 77.59
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.59
    rCSI 3.34%
    PRS 79.11
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.49
    rCSI 7.36%
    PRS 90.7
  • choroid plexus epithelial cell CL0000706
    CSI 2.45
    rCSI 4.01%
    PRS 83.9
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.43
    rCSI 2.9%
    PRS 78.05
  • type L enteroendocrine cell CL0002279
    CSI 2.37
    rCSI 4.45%
    PRS 92.7
  • retina horizontal cell CL0000745
    CSI 2.31
    rCSI 3.52%
    PRS 87.64
  • enteric neuron CL0007011
    CSI 2.22
    rCSI 32.77%
    PRS 92.29
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.19
    rCSI 4.92%
    PRS 78.49
  • muscle cell CL0000187
    CSI 2.18
    rCSI 4.48%
    PRS 93.67
  • cone retinal bipolar cell CL0000752
    CSI 2.14
    rCSI 27.98%
    PRS 87.67
  • cerebral cortex endothelial cell CL1001602
    CSI 2.13
    rCSI 3.68%
    PRS 85.43
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.79
    rCSI 3.01%
    PRS 78.03
  • enteroendocrine cell of colon CL0009042
    CSI 1.79
    rCSI 8.38%
    PRS 92.79
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.69
    rCSI 3.72%
    PRS 93.52
  • glial cell CL0000125
    CSI 1.68
    rCSI 6.4%
    PRS 84.37
  • midbrain dopaminergic neuron CL2000097
    CSI 1.54
    rCSI 9.87%
    PRS 85.15
  • diffuse bipolar 3a cell CL4033029
    CSI 1.54
    rCSI 10.46%
    PRS 82.94
  • invaginating midget bipolar cell CL4033034
    CSI 1.45
    rCSI 8.56%
    PRS 82.06
  • amacrine cell CL0000561
    CSI 1.33
    rCSI 3.87%
    PRS 82.48
  • neuroendocrine cell CL0000165
    CSI 1.22
    rCSI 4.72%
    PRS 93.68
  • diffuse bipolar 6 cell CL4033032
    CSI 1.16
    rCSI 6.1%
    PRS 80.68
  • melanocyte of skin CL1000458
    CSI 1.16
    rCSI 1.57%
    PRS 62.04
  • retinal ganglion cell CL0000740
    CSI 1.13
    rCSI 2.49%
    PRS 80.43
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.1
    rCSI 2.68%
    PRS 75.81
  • cerebellar neuron CL1001611
    CSI 1.01
    rCSI 8.92%
    PRS 78.81
  • dopaminergic neuron CL0000700
    CSI 1
    rCSI 5.63%
    PRS 80.25
  • type EC enteroendocrine cell CL0000577
    CSI 0.91
    rCSI 3.22%
    PRS 91.86
  • serotonergic neuron CL0000850
    CSI 0.89
    rCSI 3.98%
    PRS 76.63
  • diffuse bipolar 3b cell CL4033030
    CSI 0.73
    rCSI 4.82%
    PRS 85.13
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.71
    rCSI 2.68%
    PRS 78.24
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.65
    rCSI 3.53%
    PRS 93.07
  • pancreatic epsilon cell CL0005019
    CSI 0.64
    rCSI 2.98%
    PRS 94.01
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.63
    rCSI 2.27%
    PRS 76.03
  • flat midget bipolar cell CL4033033
    CSI 0.62
    rCSI 4.42%
    PRS 81.51
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.59
    rCSI 1.84%
    PRS 81
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.57
    rCSI 1.78%
    PRS 79.35
  • Cajal-Retzius cell CL0000695
    CSI 0.48
    rCSI 3.73%
    PRS 92.33

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.

Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PCBP4](/details-gene/57060) (Poly(rC) Binding Protein 4) is a protein-coding gene located on chromosome 3p21.2. As a member of the KH-domain RNA-binding protein subfamily ([Link](https://doi.org/10.1006/geno.2000.6244)), it functions primarily as an RNA-binding protein involved in the post-transcriptional regulation of gene expression. Its molecular activities include binding to mRNA, DNA, and other proteins, which it utilizes to regulate processes such as mRNA stability ([GO:0043488](https://www.ebi.ac.uk/QuickGO/term/GO:0043488)) and splicing ([GO:0048025](https://www.ebi.ac.uk/QuickGO/term/GO:0048025)). Expression data highlights its significant role in the nervous system, with particularly high and specific expression in retinal neurons, including [OFF-bipolar cell](/details-cell/CL0000750)s and [ON-bipolar cell](/details-cell/CL0000749)s. Its functional annotations strongly link it to cell cycle control, particularly DNA damage checkpoints and transcriptional regulation by TP53. ## Cellular Roles and Expression Landscape The expression profile of [PCBP4](/details-gene/57060) indicates a specialized role, primarily within the central and peripheral nervous systems, with a notable concentration in the retina. **Overall**, the gene shows the highest significance in neuronal cell types responsible for visual signal processing. It is a top marker for both [OFF-bipolar cell](/details-cell/CL0000750)s (CSI: 26.37) and [ON-bipolar cell](/details-cell/CL0000749)s (CSI: 21.85), which are critical for transmitting signals from photoreceptors. High significance is also observed in [retinal cone cell](/details-cell/CL0000573)s (CSI: 21.13) and [retinal rod cell](/details-cell/CL0000604)s (CSI: 5.14), suggesting its involvement in the function of photoreceptors themselves. Beyond the retina, [PCBP4](/details-gene/57060) is significantly expressed in [peripheral nervous system neuron](/details-cell/CL2000032)s, [interneuron](/details-cell/CL0000099)s, and neuronal precursor cells like [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s. This pattern suggests a broader role in neuronal maintenance, development, or function. Moderate significance in non-neuronal cells such as [epithelial cell](/details-cell/CL0000066)s, [bronchus fibroblast of lung](/details-cell/CL2000093)s, and [progenitor cell](/details-cell/CL0011026)s suggests its functions may extend to cellular homeostasis and proliferation in diverse tissues. Its localization in both the cytoplasm ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)) and nucleus ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) is consistent with its role in regulating mRNA processing and stability ([Link](https://doi.org/10.1128/mcb.23.23.8405-8415.2003)). ## Pathways and Molecular Function Functionally, [PCBP4](/details-gene/57060) is annotated as a multifunctional nucleic acid-binding protein. Its molecular functions are centered on binding RNA ([GO:0003723](https://www.ebi.ac.uk/QuickGO/term/GO:0003723)), particularly mRNA ([GO:0003729](https://www.ebi.ac.uk/QuickGO/term/GO:0003729)), and DNA ([GO:0003677](https://www.ebi.ac.uk/QuickGO/term/GO:0003677)). This binding capacity is translated into key biological processes, including the regulation of mRNA stability and splicing, as well as the regulation of transcription by RNA polymerase II ([GO:0006357](https://www.ebi.ac.uk/QuickGO/term/GO:0006357)). Analysis of Reactome pathways reveals a profound involvement of [PCBP4](/details-gene/57060) in the cellular response to DNA damage and cell cycle control. It is implicated in numerous pathways related to the tumor suppressor TP53, including [Transcriptional regulation by tp53](/details-pathway/R-HSA-3700989), [P53-dependent g1 dna damage response](/details-pathway/R-HSA-69563), and the [Transcriptional activation of cell cycle inhibitor p21](/details-pathway/R-HSA-69895). This network of interactions suggests that [PCBP4](/details-gene/57060) may function as a crucial mediator of TP53-induced cell cycle arrest by post-transcriptionally regulating the expression of key cell cycle genes. Its connection to general pathways like [Gene expression (transcription)](/details-pathway/R-HSA-74160) and [Cell cycle](/details-pathway/R-HSA-1640170) underscores its fundamental role in cellular homeostasis. ## Research Directions The available data suggests that [PCBP4](/details-gene/57060) is a key post-transcriptional regulator with specialized roles in the nervous system and a general function in cell cycle control. This duality opens several avenues for future research. **Proposed Hypotheses:** 1. Given its high and specific expression in retinal neurons, [PCBP4](/details-gene/57060) may be essential for maintaining the highly specialized transcriptomes of these cells. It likely stabilizes mRNAs encoding proteins critical for phototransduction, synaptic transmission, or the structural integrity of photoreceptors and bipolar cells. 2. Based on its strong linkage to TP53 pathways, [PCBP4](/details-gene/57060) may function as a downstream effector that mediates p53-dependent cell cycle arrest. In response to genotoxic stress, [PCBP4](/details-gene/57060) could be induced or activated to selectively bind and stabilize the mRNA of cell cycle inhibitors like CDKN1A (p21), thereby enforcing G1/S checkpoint control. **Experimental Approach:** To test the hypothesis regarding its role in retinal neurons, a compelling experiment would involve the use of human pluripotent stem cell (hPSC)-derived retinal organoids. CRISPR-Cas9-mediated knockout of [PCBP4](/details-gene/57060) could be performed in hPSCs before differentiation. The resulting [PCBP4](/details-gene/57060)-null organoids could then be compared to isogenic controls. Key analyses would include single-cell RNA-sequencing to identify cell-type-specific transcriptomic changes, particularly in bipolar and photoreceptor cells, and functional assays such as micro-electrode array recordings to assess defects in light-evoked electrical activity. **Therapeutic Potential:** The deep involvement of [PCBP4](/details-gene/57060) in TP53-mediated cell cycle regulation makes it a potential factor in oncology. If its function in promoting cell cycle arrest is lost in certain cancers (e.g., retinoblastoma or neuroblastoma, given its expression pattern), it could act as a tumor suppressor. In such cases, therapeutic strategies aimed at restoring [PCBP4](/details-gene/57060) function or expression could be explored. Conversely, if it were found to stabilize pro-survival mRNAs in a cancer-specific context, it would become a candidate for therapeutic **inhibition**. Its specificity to certain cell lineages suggests that targeting it may have a favorable therapeutic window, though further investigation into its role in disease is required.

Genular Protein ID: 305035873

Symbol: PCBP4_HUMAN

Name: Poly(rC)-binding protein 4

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 10936052

Title: Identification of two novel mammalian genes establishes a subfamily of KH-domain RNA-binding proteins.

PubMed ID: 10936052

DOI: 10.1006/geno.2000.6244

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14612387

Title: A novel set of nuclear localization signals determine distributions of the alphaCP RNA-binding proteins.

PubMed ID: 14612387

DOI: 10.1128/mcb.23.23.8405-8415.2003

Sequence Information:

  • Length: 403
  • Mass: 41482
  • Checksum: 3D99F762A9471265
  • Sequence:
  • MSGSDGGLEE EPELSITLTL RMLMHGKEVG SIIGKKGETV KRIREQSSAR ITISEGSCPE 
    RITTITGSTA AVFHAVSMIA FKLDEDLCAA PANGGNVSRP PVTLRLVIPA SQCGSLIGKA 
    GTKIKEIRET TGAQVQVAGD LLPNSTERAV TVSGVPDAII LCVRQICAVI LESPPKGATI 
    PYHPSLSLGT VLLSANQGFS VQGQYGAVTP AEVTKLQQLS SHAVPFATPS VVPGLDPGTQ 
    TSSQEFLVPN DLIGCVIGRQ GSKISEIRQM SGAHIKIGNQ AEGAGERHVT ITGSPVSIAL 
    AQYLITACLE TAKSTSGGTP SSAPADLPAP FSPPLTALPT APPGLLGTPY AISLSNFIGL 
    KPMPFLALPP ASPGPPPGLA AYTAKMAAAN GSKKAERQKF SPY