Details for: CABLES2

Gene ID: 81928

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: CABLES2

Ensembl ID: ENSG00000149679

Description: Cdk5 and Abl enzyme substrate 2

Selected Context(s): 

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.18
    rCSI 3.8%
    PRS 99.91
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.03
    rCSI 3.77%
    PRS 99.92

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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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 [CABLES2](/details-gene/81928) (Cdk5 and Abl enzyme substrate 2) is a protein-coding gene located on chromosome 20q13.33. As its name implies, it functions as a substrate for key kinases, positioning it as a signaling intermediate involved in critical cellular processes. Functional annotations strongly link [CABLES2](/details-gene/81928) to the [regulation of cell cycle](/details-ontology/GO:0051726) and [cell division](/details-ontology/GO:0051301). Expression data from the **Overall** context indicates that its role is particularly significant within the central nervous system, showing high expression specifically in neuronal subtypes such as [VIP GABAergic cortical interneurons](/details-cell/CL4023016) and [pvalb GABAergic cortical interneurons](/details-cell/CL4023018). This suggests a specialized function in regulating the proliferation or maintenance of these inhibitory neuron populations. ## Cellular Roles and Expression Landscape The expression profile of [CABLES2](/details-gene/81928) highlights a prominent role in specific subsets of central nervous system cells. **Overall**, the gene demonstrates its highest significance in [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 3.18) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 3.03). This restricted, high-significance expression pattern is consistent with a role in defining the functional state or developmental lineage of these specific inhibitory interneurons. Interestingly, pathway annotations also point towards a function in hematopoiesis, particularly in [megakaryocyte development and platelet production](/details-pathway/R-HSA-983231). While this role is not reflected in the top-ranked cell types from the provided **Overall** context, it suggests that [CABLES2](/details-gene/81928) may have distinct, context-dependent functions in different biological systems, such as the nervous system and the bone marrow. ## Pathways and Molecular Function [CABLES2](/details-gene/81928) is functionally annotated to the biological processes of [cell division](/details-ontology/GO:0051301) and the [regulation of cell cycle](/details-ontology/GO:0051726). Its identity as a substrate for cyclin-dependent kinase 5 (CDK5) and Abelson murine leukemia viral oncogene homolog 1 (ABL1) places it directly within kinase signaling cascades that govern cellular proliferation and differentiation. Proteomic studies have provided evidence of its phosphorylation, supporting its role as a kinase substrate within the cell cycle ([Link](https://doi.org/10.1016/j.molcel.2008.07.007)) and in other signaling contexts like T-cell receptor activation ([Link](https://doi.org/10.1126/scisignal.2000007)). Furthermore, its involvement in the Reactome pathways [Factors involved in megakaryocyte development and platelet production](/details-pathway/R-HSA-983231) and [Hemostasis](/details-pathway/R-HSA-109582) suggests a role in the maturation of hematopoietic lineages. In this context, [CABLES2](/details-gene/81928) may act as a downstream effector of kinase signaling pathways that control the complex process of megakaryocyte differentiation and the subsequent formation of platelets. ## Research Directions The apparent dichotomy between the high expression of [CABLES2](/details-gene/81928) in specific neurons and its annotated function in hematopoiesis presents intriguing avenues for future research. Understanding how this single gene contributes to such distinct biological systems is a key challenge. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis on Neuronal Function:** [CABLES2](/details-gene/81928) phosphorylation by CDK5 is a critical checkpoint for cell cycle exit and terminal differentiation in GABAergic interneuron precursors during cortical development. Its sustained high expression in mature interneurons may indicate an additional role in maintaining their differentiated state or synaptic function. 2. **Hypothesis on Hematopoietic Function:** Within the hematopoietic system, [CABLES2](/details-gene/81928) functions as a signaling adapter that integrates inputs from multiple kinases to regulate the transcriptional program governing megakaryocyte maturation. Its dysregulation could therefore be implicated in proliferative disorders of the megakaryocytic lineage. **Experimental Approach:** To test the hypothesis regarding its role in neuronal development, a robust experimental plan could be implemented. One could use CRISPR-Cas9 to generate a [CABLES2](/details-gene/81928) knockout in human induced pluripotent stem cells (iPSCs). These iPSCs could then be directed to differentiate into cortical interneurons. A comparative transcriptomic and proteomic analysis of knockout versus wild-type cells at various stages of differentiation would reveal defects in cell cycle progression, lineage commitment, and maturation, thereby clarifying the specific role of [CABLES2](/details-gene/81928) in neurogenesis. **Therapeutic Potential:** As a component of cell cycle regulatory pathways, [CABLES2](/details-gene/81928) could be considered a potential target for therapeutic intervention, particularly in oncology. Inhibition of its function might be beneficial in cancers driven by hyperactive CDK or ABL kinases. However, its high expression in specific neuronal populations raises significant concerns about potential on-target neurological toxicity. Furthermore, as a kinase substrate rather than a kinase itself, it represents a more challenging drug target. Any therapeutic strategy would likely require the development of highly specific inhibitors of the protein-protein interaction with its upstream kinases, a non-trivial undertaking.

Genular Protein ID: 664534850

Symbol: CABL2_HUMAN

Name: CDK5 and ABL1 enzyme substrate 2

UniProtKB Accession Codes:

Q9BTV7 Q5JWL0 Q9BYK0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 ExpressionAtlas 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 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 1 RefSeq 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: 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: 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

Sequence Information:

  • Length: 478
  • Mass: 52235
  • Checksum: 98E99EC72F7573EB
  • Sequence:
    • MAAAAAGGAP GPAPGPAGPP PPAAPTSAAR APPQALRRRG DSRRRQAALF FLNNISLDGR 
PPSLGPGGEK PPPPPAEARE PPAPPPPEPP TGLPARTPAP QGLLSPTQVP TGLGLDGQRQ 
RKRVTSQRCS LEFLEDAVGC APAQRTKHTS GSPRHKGLKK THFIKNMRQY DTRNSRIVLI 
CAKRSLCAAF SVLPYGEGLR ISDLRVDSQK QRHPSGGVSV SSEMVFELEG VELGADGKVV 
SYAKFLYPTN ALVTHKSDSH GLLPTPRPSV PRTLPGSRHK PAPTKSAPAS TELGSDVGDT 
LEYNPNLLDD PQWPCGKHKR VLIFASYMTT VIEYVKPSDL KKDMNETFRE KFPHVKLTLS 
KIRSLKREMR SLSEECSLEP VTVAMAYVYF EKLVLQGKLS KQNRKLCAGA CVLLAAKISS 
DLRKSGVTQL IDKLEERFRF NRRDLIGFEF TVLVALELAL YLPENQVLPH YRRLTQQF