Details for: SPDYE5

Gene ID: 442590

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: SPDYE5

Ensembl ID: ENSG00000170092

Description: speedy/RINGO cell cycle regulator family member E5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Positive regulation of cyclin-dependent protein serine/threonine kinase activity
    (GO:0045737)
  • Protein kinase binding
    (GO:0019901)

Significant Cells

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

  • inhibitory interneuron CL0000498
    CSI 5.68
    rCSI 13.11%
    PRS 94.86
  • interneuron CL0000099
    CSI 4.25
    rCSI 8.53%
    PRS 96.57
  • hepatic stellate cell CL0000632
    CSI 4.05
    rCSI 15.16%
    PRS 97.18
  • regular atrial cardiac myocyte CL0002129
    CSI 3.7
    rCSI 11.92%
    PRS 96.24
  • adipocyte CL0000136
    CSI 3.04
    rCSI 3.9%
    PRS 95.36
  • contractile cell CL0000183
    CSI 2.35
    rCSI 6.95%
    PRS 98.8
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.28
    rCSI 7.12%
    PRS 95.24
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.23
    rCSI 2.77%
    PRS 93.63
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.93
    rCSI 4.69%
    PRS 93.19
  • alveolar macrophage CL0000583
    CSI 1.75
    rCSI 2.89%
    PRS 98.53
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.68
    rCSI 2.7%
    PRS 94.6
  • melanocyte of skin CL1000458
    CSI 1.63
    rCSI 2.22%
    PRS 83.16
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.32
    rCSI 4.13%
    PRS 94.84
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.1
    rCSI 4.15%
    PRS 94.1
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.05
    rCSI 3.78%
    PRS 93.54
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.96
    rCSI 6.01%
    PRS 95.55
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.88
    rCSI 5.17%
    PRS 94.3
  • ON midget ganglion cell CL4033046
    CSI 0.37
    rCSI 7.58%
    PRS 94
  • direct pathway medium spiny neuron CL4023026
    CSI 0.28
    rCSI 6.72%
    PRS 92.54

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 [SPDYE5](/details-gene/442590) is a protein-coding gene located on human chromosome 7 whose discovery was part of the large-scale sequencing of this chromosome ([Link](https://doi.org/10.1038/nature01782)). It belongs to the speedy/RINGO family of cell cycle regulators. Functionally, [SPDYE5](/details-gene/442590) is annotated as a positive regulator of cyclin-dependent protein kinase (CDK) activity, a role it likely performs through direct protein kinase binding. **Overall**, its expression landscape is distinctive, showing the highest significance in a variety of neuronal subtypes, most notably [inhibitory interneuron](/details-cell/CL0000498)s. Additionally, it is a significant marker in several other specialized, terminally differentiated cell types such as [hepatic stellate cell](/details-cell/CL0000632)s and [regular atrial cardiac myocyte](/details-cell/CL0002129)s. This pattern suggests that despite its classification as a cell cycle regulator, [SPDYE5](/details-gene/442590) likely performs non-canonical functions related to the maintenance and specialized activities of post-mitotic cells. ## Cellular Roles and Expression Landscape The expression profile of [SPDYE5](/details-gene/442590) indicates a highly specialized role across diverse tissues, with a particular enrichment in the central nervous system. **Overall**, it demonstrates the highest significance in neural populations, including [inhibitory interneuron](/details-cell/CL0000498) (CSI: 5.68), [interneuron](/details-cell/CL0000099) (CSI: 4.25), and several specific cortical neuron subtypes such as [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036) and [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040). This strong and specific neuronal signature suggests a critical function in neuronal biology. Beyond the nervous system, [SPDYE5](/details-gene/442590) is also a significant marker in other specialized cell types. These include [hepatic stellate cell](/details-cell/CL0000632) (CSI: 4.05), [regular atrial cardiac myocyte](/details-cell/CL0002129) (CSI: 3.70), and [adipocyte](/details-cell/CL0000136) (CSI: 3.04). The high significance of a cell cycle-associated gene in these largely post-mitotic or quiescent cells is notable. This expression pattern suggests that [SPDYE5](/details-gene/442590) may be co-opted in these contexts to regulate CDK activities related to processes other than cell division, such as cellular metabolism, contractility, or response to injury. ## Pathways and Molecular Function The known molecular function of [SPDYE5](/details-gene/442590) is centered on the regulation of cell cycle machinery. According to Gene Ontology annotations, it is involved in the **positive regulation of cyclin-dependent protein serine/threonine kinase activity** ([GO:0045737](https://www.ebi.ac.uk/QuickGO/term/GO:0045737)). This regulatory action is likely mediated by its ability for **protein kinase binding** ([GO:0019901](https://www.ebi.ac.uk/QuickGO/term/GO:0019901)). Members of the Speedy/RINGO family are known to bind and activate CDKs directly, independent of cyclins. While this function is canonically tied to controlling entry into and progression through mitosis, the expression of [SPDYE5](/details-gene/442590) in terminally differentiated cells like neurons and cardiac myocytes points towards non-canonical roles. In these cells, CDKs (such as CDK5) are known to regulate a wide array of processes including synaptic plasticity, cytoskeletal dynamics, and gene transcription. Therefore, the primary role of [SPDYE5](/details-gene/442590) in these contexts may be to fine-tune the activity of specific CDKs to support the specialized functions of these non-dividing cells. ## Research Directions The unique expression pattern of [SPDYE5](/details-gene/442590) in post-mitotic cells, despite its role as a cell cycle regulator, provides fertile ground for future investigation. **Proposed Hypotheses:** 1. In the central nervous system, [SPDYE5](/details-gene/442590) modulates synaptic function in specific interneuron populations by regulating the activity of non-canonical kinases like CDK5, thereby influencing neuronal excitability and circuit integration rather than cell proliferation. 2. In [regular atrial cardiac myocyte](/details-cell/CL0002129)s, [SPDYE5](/details-gene/442590) participates in the regulation of excitation-contraction coupling or metabolic homeostasis by modulating CDK activity in response to physiological stress or hormonal signals. **Suggested Experimental Approach:** To test the hypothesis regarding its role in neuronal function, a multi-pronged approach could be employed. A conditional knockout of [SPDYE5](/details-gene/442590) in specific neuronal subtypes (e.g., using a Cre-Lox system with a Pvalb-Cre driver line) could be generated in mice. Brain slices from these animals could be subjected to electrophysiological analysis, such as patch-clamp recordings, to measure intrinsic firing properties and synaptic transmission in targeted interneurons. Concurrently, proteomics analysis using co-immunoprecipitation with an [SPDYE5](/details-gene/442590) antibody in neuronal lysates could identify its specific kinase binding partners (e.g., CDK1, CDK2, CDK5) in a post-mitotic context, clarifying the direct molecular mechanism. **Therapeutic Potential:** The therapeutic potential of targeting [SPDYE5](/details-gene/442590) is currently ambiguous and challenging. While inhibiting cell cycle regulators is a proven strategy in oncology, the high significance of [SPDYE5](/details-gene/442590) in healthy, non-proliferating neurons and cardiac myocytes raises significant safety concerns. Systemic inhibition could lead to severe neurotoxicity or cardiotoxicity. Therefore, [SPDYE5](/details-gene/442590) is not an attractive target for broad inhibition. Any therapeutic exploration would require a deep understanding of its context-specific roles and the development of highly targeted delivery systems to restrict its effect to pathological cells, which is not supported by the current data.

Genular Protein ID: 478257662

Symbol: SPDE5_HUMAN

Name: Speedy protein E5

UniProtKB Accession Codes:

A6NIY4 A0A096LPK5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 EMBL 1 Ensembl 1 ExpressionAtlas 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 InterPro 1 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

Sequence Information:

  • Length: 402
  • Mass: 47997
  • Checksum: F11F4279DCF6A4B5
  • Sequence:
    • MDRTETRFRK RGQITEKITT SRQPQPQNEQ SPQRSTSGYP LQEVVDDEVL GPSAPGVDPS 
PPCRSLGWKR KREWSDESAE EPEKELAPEP EETWVVEMLC GLKMKLKQQR VSPILPEHHK 
GFNSQLAPGV DPSPPHRSFC WKRKMEWWDE SEESLEEEPR KVLAPEPEEI WVAEMLCGLK 
MKLKRRRVSL VLPEHHEAFN RLLEDPVIKR FLAWDKDLRV SDKYLLAMVI AYFSRAGFPS 
WQYQRIHFFL ALYLANDMEE DDEDSKQNIF HFLYGKNRSR IPLLRKRWFQ LGRSMNPRAR 
KKRSRIPLLR KRRFQLGRSM NPRARKNRSR IPLLRKRRFQ LGRSMNLRAR KNRSQIVLFQ 
KRRFQFFCSM SGRAWVSPEE LEEIQAYDPE HWVWARDRAH LS