Details for: CDK15

Gene ID: 65061

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: CDK15

Ensembl ID: ENSG00000138395

Description: cyclin dependent kinase 15

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • basophil CL0000767
    CSI 5.68
    rCSI 12.01%
    PRS 99.21
  • melanocyte CL0000148
    CSI 5.11
    rCSI 3.78%
    PRS 98.64
  • cerebellar granule cell CL0001031
    CSI 3.85
    rCSI 5.66%
    PRS 97.73
  • granulocyte CL0000094
    CSI 2.84
    rCSI 4.34%
    PRS 99.3

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
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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 Cyclin-dependent kinase 15, or [CDK15](/details-gene/65061), is a protein-coding gene located on chromosome 2 that encodes a member of the cyclin-dependent protein serine/threonine kinase family. Its primary molecular functions include ATP binding, cyclin binding, and protein phosphorylation, which are central to its role in regulating the cell cycle. Beyond its general cell cycle functions, research has identified a specific anti-apoptotic role for [CDK15](/details-gene/65061), where it can phosphorylate the protein survivin to protect cells from TRAIL-induced apoptosis ([Link](https://doi.org/10.1016/j.bbrc.2014.05.070)). Expression data indicates that [CDK15](/details-gene/65061) has a specialized role, showing significant expression in diverse cell types including immune [basophils](/details-cell/CL0000767), pigment-producing [melanocytes](/details-cell/CL0000148), and neuronal [cerebellar granule cells](/details-cell/CL0001031). ## Cellular Roles and Expression Landscape The expression profile of [CDK15](/details-gene/65061) suggests it performs specialized functions rather than acting as a ubiquitous cell cycle regulator. **Overall**, the gene's significance is most pronounced in a select group of distinct cell types. It is most significant in [basophils](/details-cell/CL0000767) (CSI: 5.68), a type of [granulocyte](/details-cell/CL0000094) (CSI: 2.84) critical for allergic and inflammatory responses, suggesting a potential involvement in regulating the lifespan or activation of these immune cells. Secondly, [CDK15](/details-gene/65061) shows high significance in [melanocytes](/details-cell/CL0000148) (CSI: 5.11), the cells responsible for producing melanin pigment. This may point to a role in protecting these cells from environmental stressors like UV radiation. Finally, its notable significance in [cerebellar granule cells](/details-cell/CL0001031) (CSI: 3.85) indicates a potential function within the central nervous system, possibly related to neuronal development, maintenance, or survival. ## Pathways and Molecular Function [CDK15](/details-gene/65061) is functionally annotated as a cyclin-dependent protein serine/threonine kinase ([GO:0004693](https://www.ebi.ac.uk/QuickGO/term/GO:0004693)). Its core molecular activities involve binding to both ATP ([GO:0005524](https://www.ebi.ac.uk/QuickGO/term/GO:0005524)) and cyclin partners ([GO:0030332](https://www.ebi.ac.uk/QuickGO/term/GO:0030332)) to execute its catalytic function. This activity primarily contributes to biological processes such as protein phosphorylation ([GO:0006468](https://www.ebi.ac.uk/QuickGO/term/GO:0006468)) and the regulation of cell cycle phase transitions ([GO:1901987](https://www.ebi.ac.uk/QuickGO/term/GO:1901987)). A key characterized function of [CDK15](/details-gene/65061) is its ability to attenuate TRAIL-induced apoptosis. This is achieved through the phosphorylation of the anti-apoptotic protein survivin at the threonine 34 residue, which is thought to enhance survivin's protective function ([Link](https://doi.org/10.1016/j.bbrc.2014.05.070)). This specific anti-apoptotic role may explain its significance in the diverse cell types where it is expressed. For instance, this mechanism could be critical for the survival of long-lived [cerebellar granule cells](/details-cell/CL0001031), for protecting [melanocytes](/details-cell/CL0000148) from UV-induced damage, or for modulating the lifespan of short-lived immune cells like [basophils](/details-cell/CL0000767). Its localization within the [cytoplasm](/details-cell/GO:0005737) and [nucleus](/details-cell/GO:0005634) is consistent with its roles in regulating both cytosolic and nuclear events. ## Research Directions The specific expression pattern of [CDK15](/details-gene/65061) and its known anti-apoptotic function open several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in [melanocytes](/details-cell/CL0000148), [CDK15](/details-gene/65061) may act as a key survival factor that protects these cells against UV radiation-induced apoptosis. Consequently, its dysregulation could be a contributing factor to the development and therapeutic resistance of melanoma. 2. The high significance of [CDK15](/details-gene/65061) in [basophils](/details-cell/CL0000767) suggests it is a critical regulator of their survival and function during allergic inflammation. Its activity may modulate the threshold for degranulation or prolong the cellular lifespan at sites of inflammation. **Suggested Experimental Approach:** To test the hypothesis regarding the role of [CDK15](/details-gene/65061) in melanoma, a functional genomics approach could be employed. One could utilize CRISPR-Cas9 to generate [CDK15](/details-gene/65061) knockout and control (wild-type) human melanoma cell lines. These cell lines would then be exposed to controlled doses of UV-B radiation. The subsequent rate of apoptosis could be quantified via flow cytometry using Annexin V and propidium iodide staining. A significant increase in apoptosis in the knockout cells compared to controls would confirm the protective role of [CDK15](/details-gene/65061). Furthermore, western blot analysis could be used to confirm the loss of survivin phosphorylation at Thr34 in the knockout cells post-stimulus. **Therapeutic Potential:** The established role of [CDK15](/details-gene/65061) in promoting cell survival by inhibiting apoptosis makes it an attractive therapeutic target, particularly in oncology. As an enzyme, it is amenable to targeting with small-molecule inhibitors. The therapeutic strategy would be **inhibition**, aiming to sensitize cancer cells to apoptosis-inducing agents. For malignancies like melanoma, where [CDK15](/details-gene/65061) expression may contribute to resistance, a specific [CDK15](/details-gene/65061) inhibitor could be used in combination with standard chemotherapy or targeted therapies to enhance their efficacy. However, the expression of [CDK15](/details-gene/65061) in neuronal and immune cells raises potential concerns about on-target, off-tumor toxicity, which would require careful evaluation in preclinical models.

Genular Protein ID: 1692124439

Symbol: CDK15_HUMAN

Name: Cyclin-dependent kinase 15

UniProtKB Accession Codes:

Q96Q40 A8K8R9 B8ZZX0 C9J1N8 C9K003 F8W6H8 Q4ZG86 Q53TV1 Q6ZMR9 Q8IUP1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 1 CPTAC 1 CTD 1 ChEBI 13 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 DrugCentral 1 EC 2 EMBL 8 Ensembl 5 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 5 Rhea 6 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11586298

Title: A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.

PubMed ID: 11586298

DOI: 10.1038/ng1001-166

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 12471243

Title: The protein kinase complement of the human genome.

PubMed ID: 12471243

DOI: 10.1126/science.1075762

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

PubMed ID: 24866247

Title: ALS2CR7 (CDK15) attenuates TRAIL induced apoptosis by inducing phosphorylation of survivin Thr34.

PubMed ID: 24866247

DOI: 10.1016/j.bbrc.2014.05.070

Sequence Information:

  • Length: 435
  • Mass: 49023
  • Checksum: B415BBBE322EAB33
  • Sequence:
    • MGQELCAKTV QPGCSCYHCS EGGEAHSCRR SQPETTEAAF KLTDLKEASC SMTSFHPRGL 
QAARAQKFKS KRPRSNSDCF QEEDLRQGFQ WRKSLPFGAA SSYLNLEKLG EGSYATVYKG 
ISRINGQLVA LKVISMNAEE GVPFTAIREA SLLKGLKHAN IVLLHDIIHT KETLTFVFEY 
MHTDLAQYMS QHPGGLHPHN VRLFMFQLLR GLAYIHHQHV LHRDLKPQNL LISHLGELKL 
ADFGLARAKS IPSQTYSSEV VTLWYRPPDA LLGATEYSSE LDIWGAGCIF IEMFQGQPLF 
PGVSNILEQL EKIWEVLGVP TEDTWPGVSK LPNYNPEWFP LPTPRSLHVV WNRLGRVPEA 
EDLASQMLKG FPRDRVSAQE ALVHDYFSAL PSQLYQLPDE ESLFTVSGVR LKPEMCDLLA 
SYQKGHHPAQ FSKCW