Details for: ECE2

Gene ID: 9718

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: ECE2

Ensembl ID: ENSG00000145194

Description: endothelin converting enzyme 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 4.65
    rCSI 8.21%
    PRS 90.55
  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.23
    rCSI 5.05%
    PRS 90.81
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 4.16
    rCSI 6.98%
    PRS 90.92
  • retinal ganglion cell CL0000740
    CSI 3.95
    rCSI 8.73%
    PRS 91.26
  • neuron CL0000540
    CSI 3.88
    rCSI 10.32%
    PRS 88.56
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.46
    rCSI 4.31%
    PRS 89.32
  • cerebellar granule cell CL0001031
    CSI 3.33
    rCSI 4.9%
    PRS 93.84
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.09
    rCSI 3.98%
    PRS 91.48
  • respiratory hillock cell CL4030023
    CSI 2.62
    rCSI 4.66%
    PRS 98
  • retina horizontal cell CL0000745
    CSI 2.58
    rCSI 3.93%
    PRS 94.96
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.54
    rCSI 4.08%
    PRS 91.28
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.33
    rCSI 5.23%
    PRS 91.08
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.12
    rCSI 6.65%
    PRS 92.49
  • club cell CL0000158
    CSI 2.11
    rCSI 3.09%
    PRS 95.16
  • GABAergic amacrine cell CL4030027
    CSI 1.41
    rCSI 4.83%
    PRS 89.02
  • amacrine cell CL0000561
    CSI 1.4
    rCSI 4.05%
    PRS 92.15
  • direct pathway medium spiny neuron CL4023026
    CSI 1.16
    rCSI 27.75%
    PRS 88.57
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.16
    rCSI 2.81%
    PRS 89.19
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.14
    rCSI 4.32%
    PRS 90.78
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.09
    rCSI 26.33%
    PRS 88.31
  • ON parasol ganglion cell CL4033052
    CSI 1.08
    rCSI 15.31%
    PRS 91.73
  • ON midget ganglion cell CL4033046
    CSI 0.86
    rCSI 17.57%
    PRS 91.42
  • OFF midget ganglion cell CL4033047
    CSI 0.86
    rCSI 17.42%
    PRS 91.69

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 Analyzed for its expression specificity (CSI Z-SCORE), Endothelin Converting Enzyme 2 ([ECE2](/details-gene/9718)) does not emerge as a defining marker for any single cell type. Instead, the data indicate that [ECE2](/details-gene/9718) is broadly and consistently expressed across a wide range of neuronal populations. This expression pattern, coupled with its known function as a metalloendopeptidase, suggests a role in a conserved and fundamental biological process common to diverse neurons, such as neuropeptide processing or general protein trafficking, rather than a function that defines cellular identity. ## Cellular Roles and Expression Landscape The expression profile of [ECE2](/details-gene/9718), when evaluated for specificity, is notable for its lack of statistical significance in distinguishing any particular cell type. In the **Overall** context, numerous cell types, predominantly neurons, exhibit a CSI (Z-SCORE) of 0.00 and high p-values (p > 0.5). This indicates that the expression level of [ECE2](/details-gene/9718) within these cells is not significantly different from the average expression across all cell types, precluding its use as a specific marker. Despite the lack of specificity, [ECE2](/details-gene/9718) appears to be an important and consistently expressed gene within the nervous system. This is supported by its high Percentile Rank Score (PRS), which remains above 88% for all listed cell types, and a maximal Effect Size (deltaVal) of 1.00. This combination suggests that while [ECE2](/details-gene/9718) is not uniquely expressed in any one cell type, its expression is reliably detected at a significant level across many of them. The gene's expression is widespread across functionally and developmentally distinct neuronal subtypes, including various GABAergic cortical interneurons ([caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064), [VIP GABAergic cortical interneuron](/details-cell/CL4023016), [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)), projection neurons ([retinal ganglion cell](/details-cell/CL0000740)), and other specialized neurons like the [cerebellar granule cell](/details-cell/CL0001031). Furthermore, its expression is also detected in non-neuronal cells such as the [astrocyte of the cerebral cortex](/details-cell/CL0002605) and the [club cell](/details-cell/CL0000158) of the respiratory system, reinforcing the hypothesis of a role in a widely utilized cellular pathway rather than a cell-identity program. ## Pathways and Molecular Function The functional annotations for [ECE2](/details-gene/9718) align with its broad but significant expression pattern in the nervous system. As a metalloendopeptidase ([GO:0004222](https://www.ebi.ac.uk/QuickGO/term/GO:0004222)), its involvement in '[Peptide hormone processing](/details-cell/GO:0016486)' and '[Protein processing](/details-cell/GO:0016485)' provides a molecular basis for its importance in neurons, which rely heavily on neuropeptides for signaling. This function is further contextualized by its association with Reactome pathways central to neuronal communication, such as '[Signaling by gpcr](/details-cell/R-HSA-372790)' and '[Peptide ligand-binding receptors](/details-cell/R-HSA-375276)'. The gene's localization to the '[Golgi membrane](/details-cell/GO:0000139)', '[Cytoplasmic vesicle membrane](/details-cell/GO:0030659)', and '[Transport vesicle membrane](/details-cell/GO:0030658)' is consistent with a role in the secretory pathway, where neuropeptide precursors are processed and packaged into vesicles for release. The broad expression across many neuron types suggests that [ECE2](/details-gene/9718) may process a wide range of substrates or be part of a general machinery essential for the maturation of secreted proteins in most, if not all, neurons. ## Research Directions The defining feature of the [ECE2](/details-gene/9718) expression profile is its breadth across neuronal types rather than its specificity to any single one. This observation leads to several testable hypotheses regarding its fundamental role in neural function. 1. **Hypothesis: ECE2 functions as a master regulator of a common neuropeptide pathway essential for diverse neuronal subtypes.** Its consistent expression across inhibitory interneurons, retinal ganglion cells, and cerebellar granule cells suggests it may process a substrate or set of substrates common to all these cell types, acting as a non-cell-specific but essential component of synaptic communication. * **Experimental Approach:** Utilize proximity-labeling proteomics (e.g., TurboID) with ECE2 as the bait in primary mixed neuronal cultures or organoids. Subsequent mass spectrometry would identify its substrate and interacting partners, revealing the common pathways it regulates across different neuronal populations. 2. **Hypothesis: The expression of ECE2 is maintained at a constitutive, homeostatic level across neurons, reflecting a 'housekeeping' role in protein processing rather than a dynamically regulated role in cell fate specification.** The lack of a significant Z-score but high PRS supports the idea of stable, above-average expression that is not fine-tuned to create cellular diversity. * **Experimental Approach:** Perform longitudinal single-cell RNA sequencing on developing cortical organoids. If [ECE2](/details-gene/9718) expression remains stable across various neuronal differentiation trajectories and mature neuronal clusters, it would support a constitutive role. This could be contrasted with known cell-type-specific transcription factors, which should show dynamic expression patterns. 3. **Hypothesis: The methyltransferase activity ([GO:0008168](https://www.ebi.ac.uk/QuickGO/term/GO:0008168)) of ECE2, in addition to its peptidase function, is critical for general membrane protein stability or trafficking within the Golgi and transport vesicles.** This dual function could explain its necessity in a wide range of cell types, including non-neuronal cells like astrocytes and club cells which also have active secretory pathways. * **Experimental Approach:** Generate cell lines (e.g., HEK293 or a neuroblastoma line) with two different ECE2 knockouts using CRISPR-Cas9: one targeting the peptidase domain and another targeting the putative methyltransferase domain. Assays measuring Golgi integrity, vesicle transport rates (e.g., using a fluorescently-tagged cargo protein), and overall secretome composition could then dissect the relative contributions of each enzymatic function. **Therapeutic Potential:** Given its broad expression, targeting [ECE2](/details-gene/9718) systemically would likely have widespread, pleiotropic effects. However, if its activity is implicated in diseases characterized by global neuropeptide dysregulation or protein processing defects, such as certain neurodegenerative or psychiatric disorders, modulating ECE2 could represent a therapeutic strategy. Any such approach would require careful consideration of on-target effects across the entire nervous system.