Details for: TP53RK

Gene ID: 112858

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: TP53RK

Ensembl ID: ENSG00000172315

Description: TP53 regulating kinase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • hematopoietic precursor cell CL0008001
    CSI 5.96
    rCSI 6.13%
    PRS 97.89
  • bronchus fibroblast of lung CL2000093
    CSI 3.96
    rCSI 3.22%
    PRS 95.06
  • placental villous trophoblast CL2000060
    CSI 3.91
    rCSI 6.05%
    PRS 93.86
  • promyelocyte CL0000836
    CSI 3.82
    rCSI 5.52%
    PRS 96.02
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.54
    rCSI 2.47%
    PRS 97.04
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.44
    rCSI 3.11%
    PRS 94.6
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.4
    rCSI 2.64%
    PRS 96.65
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.36
    rCSI 3.88%
    PRS 89.79
  • neural crest cell CL0011012
    CSI 3.27
    rCSI 2.59%
    PRS 91.25
  • perivascular cell CL4033054
    CSI 3.2
    rCSI 4.37%
    PRS 97.09
  • multi-ciliated epithelial cell CL0005012
    CSI 3.11
    rCSI 3.1%
    PRS 91.13
  • keratinocyte CL0000312
    CSI 3.04
    rCSI 2.55%
    PRS 94.72
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 3.01
    rCSI 2.74%
    PRS 98.94
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 2.97
    rCSI 2.92%
    PRS 97.92
  • common myeloid progenitor CL0000049
    CSI 2.9
    rCSI 2.34%
    PRS 96.01
  • duct epithelial cell CL0000068
    CSI 2.88
    rCSI 4.22%
    PRS 97.07
  • early lymphoid progenitor CL0000936
    CSI 2.88
    rCSI 2.53%
    PRS 97.26
  • type B pancreatic cell CL0000169
    CSI 2.81
    rCSI 6.23%
    PRS 95.13
  • pro-B cell CL0000826
    CSI 2.77
    rCSI 2.29%
    PRS 96.03
  • extravillous trophoblast CL0008036
    CSI 2.77
    rCSI 3.42%
    PRS 93.9
  • ciliated epithelial cell CL0000067
    CSI 2.69
    rCSI 2.37%
    PRS 89.06
  • epithelial cell of lung CL0000082
    CSI 2.66
    rCSI 2.2%
    PRS 96.14
  • stem cell CL0000034
    CSI 2.62
    rCSI 2.52%
    PRS 93.08
  • mesodermal cell CL0000222
    CSI 2.45
    rCSI 2.95%
    PRS 94.93
  • lung ciliated cell CL1000271
    CSI 2.33
    rCSI 2.7%
    PRS 91.41
  • radial glial cell CL0000681
    CSI 2.21
    rCSI 3.08%
    PRS 94.05
  • progenitor cell CL0011026
    CSI 2.17
    rCSI 4.62%
    PRS 90.63
  • common dendritic progenitor CL0001029
    CSI 2.15
    rCSI 2.7%
    PRS 97.69
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.13
    rCSI 6.3%
    PRS 95.17
  • ciliated cell CL0000064
    CSI 2.12
    rCSI 3.43%
    PRS 90.17
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.08
    rCSI 3.68%
    PRS 86.77
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.05
    rCSI 2.63%
    PRS 92.59
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.94
    rCSI 6.06%
    PRS 88.1
  • glioblast CL0000030
    CSI 1.87
    rCSI 2.99%
    PRS 89.87
  • mesenchymal cell CL0008019
    CSI 1.86
    rCSI 4.73%
    PRS 92.54
  • basal cell CL0000646
    CSI 1.73
    rCSI 2.32%
    PRS 93.1
  • club cell CL0000158
    CSI 1.72
    rCSI 2.52%
    PRS 92.57
  • tracheobronchial smooth muscle cell CL0019019
    CSI 1.63
    rCSI 2.88%
    PRS 96.74
  • lung pericyte CL0009089
    CSI 1.6
    rCSI 4.21%
    PRS 97.28
  • retinal cone cell CL0000573
    CSI 1.39
    rCSI 2.24%
    PRS 89.53
  • forebrain radial glial cell CL0013000
    CSI 1.1
    rCSI 3.52%
    PRS 94.85
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.84
    rCSI 1.92%
    PRS 89.49
  • primitive red blood cell CL0002355
    CSI 0.77
    rCSI 4.15%
    PRS 95.6
  • erythroid progenitor cell CL0000038
    CSI 0.61
    rCSI 3.51%
    PRS 96.21
  • eosinophil CL0000771
    CSI 0.57
    rCSI 3.73%
    PRS 98.6

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 [TP53RK](/details-gene/112858) (TP53 regulating kinase) is a protein-coding gene located on chromosome 20q13.12. It encodes a protein serine/threonine kinase that plays a crucial role in fundamental cellular processes, including gene expression, tRNA processing, and the regulation of the tumor suppressor p53. It functions as a core component of the EKC/KEOPS complex, which is involved in tRNA modification, highlighting its importance in protein synthesis. Expression data indicates that **Overall**, [TP53RK](/details-gene/112858) is most significant in highly proliferative and metabolically active cells, particularly in '[hematopoietic precursor cell](/details-cell/CL0008001)', as well as in various progenitor, fibroblast, and activated immune cell populations. Its function links transcriptional regulation with translational fidelity, positioning it as a key regulator of cell growth and stress response. ## Cellular Roles and Expression Landscape The expression profile of [TP53RK](/details-gene/112858) points to a significant role in cellular proliferation, differentiation, and high metabolic activity. **Overall**, it demonstrates the highest significance in '[hematopoietic precursor cell](/details-cell/CL0008001)' (CSI: 5.96), with notable expression in other progenitor lineages such as '[promyelocyte](/details-cell/CL0000836)', '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)', '[common myeloid progenitor](/details-cell/CL0000049)', '[neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338)', and '[neural crest cell](/details-cell/CL0011012)'. This pattern suggests that [TP53RK](/details-gene/112858) is integral to the molecular machinery that supports the rapid growth and lineage commitment of precursor cells. Beyond progenitor cells, [TP53RK](/details-gene/112858) is also highly significant in structurally and functionally active cell types, including '[bronchus fibroblast of lung](/details-cell/CL2000093)' and '[placental villous trophoblast](/details-cell/CL2000060)'. Furthermore, its relevance in the immune system is highlighted by its expression in '[plasmacytoid dendritic cell, human](/details-cell/CL0001058)', '[effector memory CD8-positive, alpha-beta T cell](/details-cell/CL0000913)', and '[activated CD8-positive, alpha-beta T cell](/details-cell/CL0000906)', which is consistent with early research identifying its expression in activated cytotoxic T-cells ([Link](https://doi.org/10.1074/jbc.m105669200)). This collective expression landscape suggests that [TP53RK](/details-gene/112858) is a key functional component in cells requiring robust transcriptional and translational output. ## Pathways and Molecular Function [TP53RK](/details-gene/112858) functions as a versatile kinase involved in several critical cellular pathways. As its name implies, it is a key participant in the '[Regulation of tp53 activity](/details-pathway/R-HSA-5633007)', specifically through '[Regulation of tp53 activity through phosphorylation](/details-pathway/R-HSA-6804756)', and exhibits '[P53 binding](/details-go/GO:0002039)' capabilities. This directly links the kinase to the canonical tumor suppressor pathway that governs cell cycle arrest, apoptosis, and DNA repair. A significant aspect of its function is its role as a core component of the '[Ekc/keops complex](/details-go/GO:0000408)' ([Link](https://doi.org/10.1093/nar/gkw1181)). This complex is essential for the N6-threonylcarbamoyladenosine (t6A) modification of tRNAs, a process critical for translational fidelity and efficiency. This function is reflected in its annotation for '[Trna processing](/details-go/GO:0008033)' and '[Trna threonylcarbamoyladenosine metabolic process](/details-go/GO:0070525)'. The requirement for accurate protein synthesis in rapidly dividing cells is consistent with its high expression in progenitor populations. The involvement of the KEOPS complex in '[Gene expression (transcription)](/details-pathway/R-HSA-74160)' and '[Chromatin remodeling](/details-go/GO:0006338)' further suggests that [TP53RK](/details-gene/112858) helps coordinate the transcriptional and translational programs necessary for cell growth and function. Mutations in other KEOPS-complex genes have been linked to developmental disorders, underscoring the critical nature of this pathway ([Link](https://doi.org/10.1038/ng.3933)). ## Research Directions The dual role of [TP53RK](/details-gene/112858) in p53 regulation and as a core component of the essential EKC/KEOPS complex presents several avenues for future research, particularly in the contexts of development and cancer biology. **Proposed Hypotheses:** 1. Given its high significance in multiple progenitor cell types ([hematopoietic precursor cell](/details-cell/CL0008001), [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338)) and its role in tRNA modification, [TP53RK](/details-gene/112858) may be indispensable for maintaining the high translational fidelity required for stem cell self-renewal and lineage-specific differentiation. Its loss could lead to proteotoxic stress and impaired developmental progression. 2. Based on its function in regulating p53 and its expression in activated T cells and tumor cell lines ([Link](https://doi.org/10.1074/jbc.m105669200)), [TP53RK](/details-gene/112858) kinase activity may act as a rheostat that suppresses p53's pro-apoptotic functions in highly proliferative states. In cancer, its overexpression could provide a survival advantage by uncoupling proliferation from cell death checkpoints. **Key Experimental Approach:** To test the hypothesis that [TP53RK](/details-gene/112858) is critical for progenitor cell function, a conditional knockout of [TP53RK](/details-gene/112858) could be generated in a mouse hematopoietic stem cell (HSC) model. The impact of its deletion on HSC self-renewal and differentiation could be assessed through competitive bone marrow transplantation assays. Subsequent single-cell RNA-sequencing (scRNA-seq) of the recovering hematopoietic compartment would reveal cell-type-specific defects in lineage commitment, while ribosome profiling (Ribo-seq) on sorted progenitor populations would directly measure changes in translational efficiency and codon-specific pausing, linking its molecular function to the cellular phenotype. **Therapeutic Potential:** As a protein kinase, [TP53RK](/details-gene/112858) is a potentially druggable target. Its roles in promoting processes essential for rapid cell growth and in regulating p53 make it an attractive candidate for cancer therapy. An inhibitor targeting the kinase activity of [TP53RK](/details-gene/112858) could theoretically disrupt the translational capacity of tumor cells and/or reactivate p53-mediated tumor suppression. Therefore, **inhibition** would be the logical therapeutic strategy. However, its importance in healthy progenitor populations suggests that systemic inhibition could lead to significant on-target toxicities, such as myelosuppression. A successful therapeutic approach would likely require a well-defined therapeutic window or targeted delivery to neoplastic cells.

Genular Protein ID: 461375600

Symbol: PRPK_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96S44 B3KU44 Q3T977 Q5JZ01 Q6NZ60 Q96FM7 Q9NQE6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CPTAC 2 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 DrugCentral 1 EC 2 EMBL 9 Ensembl 1 ExpressionAtlas 1 GO 14 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 Rhea 6 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11546806

Title: Cloning and characterization of a p53-related protein kinase expressed in interleukin-2-activated cytotoxic T-cells, epithelial tumor cell lines, and the testes.

PubMed ID: 11546806

DOI: 10.1074/jbc.m105669200

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

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: 12659830

Title: Identification of CGI-121, a novel PRPK (p53-related protein kinase)-binding protein.

PubMed ID: 12659830

DOI: 10.1016/s0006-291x(03)00333-4

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22912744

Title: The human EKC/KEOPS complex is recruited to Cullin2 ubiquitin ligases by the human tumour antigen PRAME.

PubMed ID: 22912744

DOI: 10.1371/journal.pone.0042822

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 27903914

Title: Proteomic analysis of the human KEOPS complex identifies C14ORF142 as a core subunit homologous to yeast Gon7.

PubMed ID: 27903914

DOI: 10.1093/nar/gkw1181

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

PubMed ID: 28805828

Title: Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

PubMed ID: 28805828

DOI: 10.1038/ng.3933

Sequence Information:

  • Length: 253
  • Mass: 28160
  • Checksum: 8B081DED6D2DC034
  • Sequence:
    • MAAARATTPA DGEEPAPEAE ALAAARERSS RFLSGLELVK QGAEARVFRG RFQGRAAVIK 
HRFPKGYRHP ALEARLGRRR TVQEARALLR CRRAGISAPV VFFVDYASNC LYMEEIEGSV 
TVRDYIQSTM ETEKTPQGLS NLAKTIGQVL ARMHDEDLIH GDLTTSNMLL KPPLEQLNIV 
LIDFGLSFIS ALPEDKGVDL YVLEKAFLST HPNTETVFEA FLKSYSTSSK KARPVLKKLD 
EVRLRGRKRS MVG