Details for: EPN3

Gene ID: 55040

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: EPN3

Ensembl ID: ENSG00000049283

Description: epsin 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • secretory cell CL0000151
    CSI 6.59
    rCSI 6.87%
    PRS 98.92
  • transit amplifying cell of colon CL0009011
    CSI 6.09
    rCSI 7.16%
    PRS 99.39
  • goblet cell CL0000160
    CSI 4.74
    rCSI 4.48%
    PRS 98.77
  • foveolar cell of stomach CL0002179
    CSI 3.83
    rCSI 8.15%
    PRS 99.05
  • intestine goblet cell CL0019031
    CSI 3.73
    rCSI 3.31%
    PRS 98.66
  • nasal mucosa goblet cell CL0002480
    CSI 3.68
    rCSI 4.26%
    PRS 98.51
  • duct epithelial cell CL0000068
    CSI 3.64
    rCSI 5.33%
    PRS 99.68
  • innate lymphoid cell CL0001065
    CSI 3.59
    rCSI 7.41%
    PRS 95.92
  • ciliated cell CL0000064
    CSI 3.45
    rCSI 5.59%
    PRS 97.02
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.49
    rCSI 2.4%
    PRS 98.79
  • placental villous trophoblast CL2000060
    CSI 2.4
    rCSI 3.71%
    PRS 98.48
  • club cell CL0000158
    CSI 2.11
    rCSI 3.1%
    PRS 99.02
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.09
    rCSI 2.53%
    PRS 90.54
  • basal cell of epidermis CL0002187
    CSI 1.77
    rCSI 3.14%
    PRS 87.05
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.68
    rCSI 4.25%
    PRS 98.32
  • colon goblet cell CL0009039
    CSI 1.61
    rCSI 3.82%
    PRS 99.16
  • parietal cell CL0000162
    CSI 0.73
    rCSI 6.3%
    PRS 98.51

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.

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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 [EPN3](/details-gene/55040) (Epsin 3) is a protein-coding gene located on chromosome 17q21.33. Functionally, [EPN3](/details-gene/55040) is an accessory protein involved in clathrin-mediated endocytosis, a fundamental cellular process for internalizing molecules from the cell surface. It exhibits specific binding to clathrin, phospholipids, and proteins containing EH domains, localizing to critical structures such as [clathrin-coated pits (GO:0005905)](https://www.ebi.ac.uk/QuickGO/term/GO:0005905) and vesicles. **Overall**, expression data reveals that [EPN3](/details-gene/55040) is a significant marker for various epithelial and [secretory cells (CL0000151)](/details-cell/CL0000151), including [transit amplifying cells of the colon (CL0009011)](/details-cell/CL0009011) and [goblet cells (CL0000160)](/details-cell/CL0000160). This expression pattern, combined with research showing its induction in wounded epithelia ([Link](https://doi.org/10.1074/jbc.m101663200)), suggests a key role for [EPN3](/details-gene/55040) in processes requiring high membrane turnover, such as secretion, cell migration, and tissue regeneration. ## Cellular Roles and Expression Landscape The expression profile of [EPN3](/details-gene/55040) highlights its specialized role in epithelial biology, particularly in tissues characterized by high rates of secretion and cellular turnover. **Overall**, it shows the highest significance in [secretory cells (CL0000151)](/details-cell/CL0000151) (CSI: 6.59) and [transit amplifying cells of the colon (CL0009011)](/details-cell/CL0009011) (CSI: 6.09), which are progenitor cells responsible for regenerating the colonic epithelium. This pattern is consistent across multiple mucosal surfaces, with high significance in various [goblet cells (CL0000160)](/details-cell/CL0000160), such as those in the intestine and nasal mucosa, as well as [foveolar cells of the stomach (CL0002179)](/details-cell/CL0002179). Beyond the gastrointestinal tract, [EPN3](/details-gene/55040) is also significant in other secretory and barrier epithelia, including [ciliated cells (CL0000064)](/details-cell/CL0000064), [fallopian tube secretory epithelial cells (CL4030006)](/details-cell/CL4030006), and [club cells (CL0000158)](/details-cell/CL0000158) in the respiratory system. Its expression in [basal cells of the epidermis (CL0002187)](/details-cell/CL0002187) further supports its association with regenerative cell populations. While primarily an epithelial marker, its moderate significance in [innate lymphoid cells (CL0001065)](/details-cell/CL0001065) and a subset of memory T cells may suggest a secondary role in immune cell function, potentially related to vesicle trafficking or receptor internalization. The collective data portrays [EPN3](/details-gene/55040) as a key operational gene in dynamic epithelial environments that demand robust endocytic machinery. ## Pathways and Molecular Function The functional annotations for [EPN3](/details-gene/55040) firmly place it within the cellular machinery of clathrin-mediated endocytosis. Its molecular functions include direct [clathrin binding (GO:0030276)](https://www.ebi.ac.uk/QuickGO/term/GO:0030276) and [phospholipid binding (GO:0005543)](https://www.ebi.ac.uk/QuickGO/term/GO:0005543), which are essential for recruiting clathrin to the plasma membrane and initiating the formation of endocytic vesicles. This role is corroborated by its localization to the [cytoplasmic side of the plasma membrane (GO:0009898)](https://www.ebi.ac.uk/QuickGO/term/GO:0009898), [clathrin-coated pits (GO:0005905)](https://www.ebi.ac.uk/QuickGO/term/GO:0005905), and the resulting [clathrin vesicle coat (GO:0030125)](https://www.ebi.ac.uk/QuickGO/term/GO:0030125). This core function in [endocytosis (GO:0006897)](https://www.ebi.ac.uk/QuickGO/term/GO:0006897) is highly consistent with its expression pattern in metabolically active cells. For instance, in [goblet cells (CL0000160)](/details-cell/CL0000160), efficient endocytosis is required to recycle membrane components after the exocytosis of mucin granules. In rapidly dividing [transit amplifying cells (CL0009011)](/details-cell/CL0009011) and in the context of wound healing ([Link](https://doi.org/10.1074/jbc.m101663200)), endocytosis is critical for internalizing and modulating signals from growth factor receptors that drive proliferation and migration. Therefore, [EPN3](/details-gene/55040) likely serves as a crucial facilitator of membrane trafficking events that underpin the specialized functions of diverse epithelial cell types. ## Research Directions The specific expression of [EPN3](/details-gene/55040) in regenerative and secretory epithelial populations, combined with its known induction during wound healing, opens several avenues for future research. **Proposed Hypotheses:** 1. Given its role in endocytosis and high expression in [transit amplifying cells (CL0009011)](/details-cell/CL0009011), [EPN3](/details-gene/55040) is hypothesized to be a critical regulator of epithelial proliferation and migration during tissue repair by controlling the surface availability and signaling of key growth factor receptors like EGFR. 2. In secretory cell types like [goblet cells (CL0000160)](/details-cell/CL0000160) and [fallopian tube secretory epithelial cells (CL4030006)](/details-cell/CL4030006), [EPN3](/details-gene/55040) may be essential for compensatory endocytosis, a process that retrieves excess membrane after large-scale exocytosis, thereby maintaining cellular homeostasis and readiness for subsequent secretory events. **Experimental Approach:** To test the first hypothesis regarding its role in wound healing, an *in vitro* and *in vivo* approach could be employed. * **Experiment:** Generate an [EPN3](/details-gene/55040) conditional knockout mouse model with epithelial-specific Cre drivers (e.g., KRT14-Cre for skin or Villin-Cre for intestine). * **Method:** Subject these mice and their wild-type littermates to cutaneous punch biopsy or dextran sulfate sodium (DSS)-induced colitis to model skin and intestinal injury, respectively. * **Analysis:** Monitor the rate of wound closure and epithelial restitution over time. Analyze tissue sections using immunohistochemistry to assess cell proliferation (Ki-67 staining), migration, and the localization of signaling receptors at the wound edge. This would directly determine if [EPN3](/details-gene/55040) is required for efficient epithelial repair *in vivo*. **Therapeutic Potential:** The upregulation of [EPN3](/details-gene/55040) in contexts of high epithelial turnover suggests it could be a therapeutic target in diseases characterized by aberrant epithelial proliferation, such as certain cancers (e.g., colorectal adenocarcinoma) or chronic inflammatory conditions. **Inhibition** of [EPN3](/details-gene/55040) function could potentially slow down pathological cell migration and growth. As an intracellular scaffolding protein, it is not an ideal target for antibody-based therapies but may be amenable to small molecule inhibitors designed to disrupt its protein-protein interactions with clathrin or other endocytic partners. However, the ubiquitous nature of endocytosis raises concerns about potential off-target effects, necessitating highly specific targeting strategies.

Genular Protein ID: 3138752178

Symbol: EPN3_HUMAN

Name: Epsin-3

UniProtKB Accession Codes:

Q9H201 A8K6J3 A8KAB2 Q9BVN6 Q9NWK2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 6 DMDM 1 DNASU 1 DisGeNET 1 ELM 1 EMBL 8 Ensembl 2 ExpressionAtlas 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 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 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 1 SMART 2 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: 11359770

Title: Epsin 3 is a novel extracellular matrix-induced transcript specific to wounded epithelia.

PubMed ID: 11359770

DOI: 10.1074/jbc.m101663200

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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

Sequence Information:

  • Length: 632
  • Mass: 68222
  • Checksum: 13940F2FBD6215D0
  • Sequence:
    • MTTSALRRQV KNIVHNYSEA EIKVREATSN DPWGPPSSLM SEIADLTFNT VAFTEVMGML 
WRRLNDSGKN WRHVYKALTL LDYLLKTGSE RVAHQCRENL YTIQTLKDFQ YIDRDGKDQG 
VNVREKVKQV MALLKDEERL RQERTHALKT KERMALEGIG IGSGQLGFSR RYGEDYSRSR 
GSPSSYNSSS SSPRYTSDLE QARPQTSGEE ELQLQLALAM SREEAEKPVP PASHRDEDLQ 
LQLALRLSRQ EHEKEVRSWQ GDGSPMANGA GAVVHHQRDR EPEREERKEE EKLKTSQSSI 
LDLADIFVPA LAPPSTHCSA DPWDIPGFRP NTEASGSSWG PSADPWSPIP SGTVLSRSQP 
WDLTPMLSSS EPWGRTPVLP AGPPTTDPWA LNSPHHKLPS TGADPWGASL ETSDTPGGAS 
TFDPFAKPPE STETKEGLEQ ALPSGKPSSP VELDLFGDPS PSSKQNGTKE PDALDLGILG 
EALTQPSKEA RACRTPESFL GPSASSLVNL DSLVKAPQVA KTRNPFLTGL SAPSPTNPFG 
AGEPGRPTLN QMRTGSPALG LAGGPVGAPL GSMTYSASLP LPLSSVPAGL TLPASVSVFP 
QAGAFAPQPL LPTPSSAGPR PPPPQTGTNP FL