EPN2 Gene

Name	epsin 2
Description	This gene encodes a protein which interacts with clathrin and adaptor-related protein complex 2, alpha 1 subunit. The protein is found in a brain-derived clathrin-coated vesicle fraction and localizes to the peri-Golgi region and the cell periphery. The protein is thought to be involved in clathrin-mediated endocytosis. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Epsin‐2 (EPN2) is an evolutionarily conserved ubiquitin‐binding adaptor protein that plays multifunctional roles in coordinated membrane dynamics. In general, EPN2 participates in clathrin‐mediated endocytosis by interacting with clathrin, AP‐2 and other accessory proteins to help capture and deform membranes into vesicles (see, for example."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition to this general adaptor function, EPN2 has been implicated in several specialized contexts. In lymphatic endothelial cells, it cooperates with its family member epsin‐1 to bind and promote the internalization and degradation of vascular endothelial growth factor receptor 3 (VEGFR3), thereby restricting VEGFR3 signaling and contributing to proper lymphatic valve development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the context of gametogenesis, EPN2 has been shown to be essential for oocyte meiotic maturation; its depletion disrupts actin cap formation, spindle organization, and polar body extrusion by attenuating Cdc42 activation, underscoring its role in establishing polarity and coordinating cytokinesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, studies in yeast illustrate that epsin‐2 can influence cell division by modulating septin assembly through interactions with regulatory proteins such as Bem3, thereby linking endocytic adaptor function with cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Additional research in podocytes indicates that EPN2 contributes to proper cell adhesion and the maintenance of foot process architecture by regulating signaling pathways that involve actin dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, modulation of EPN2 expression (for instance, via growth factor signals that induce its upregulation) can affect receptor turnover (such as enhanced degradation of VEGFR2), thereby influencing vascular maturation and stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these studies reveal that EPN2 functions not only as a general component of the vesicle‐forming machinery but also as a critical regulator of cell signaling and morphology in diverse physiological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J A Rosenthal, H Chen, V I Slepnev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.274.48.33959"}], "href": "https://doi.org/10.1074/jbc.274.48.33959"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10567358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10567358"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mirko Messa, Rubén Fernández-Busnadiego, Elizabeth Wen Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.03311"}], "href": "https://doi.org/10.7554/eLife.03311"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25122462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25122462"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "J A Martina, C J Bonangelino, R C Aguilar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.153.5.1111"}], "href": "https://doi.org/10.1083/jcb.153.5.1111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11381094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11381094"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaolei Liu, Satish Pasula, Hoogeun Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Temporal and spatial regulation of epsin abundance and VEGFR3 signaling are required for lymphatic valve formation and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2005413"}], "href": "https://doi.org/10.1126/scisignal.2005413"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25314967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25314967"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ling Li, Longsen Han, Jiaqi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epsin2 promotes polarity establishment and meiotic division through activating Cdc42 in mouse oocyte."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.10815"}], "href": "https://doi.org/10.18632/oncotarget.10815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27463009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27463009"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Debarati Mukherjee, Brian G Coon, Daniel F Edwards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The yeast endocytic protein Epsin 2 functions in a cell-division signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.041137"}], "href": "https://doi.org/10.1242/jcs.041137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19531587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19531587"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ying Wang, Christopher E Pedigo, Kazunori Inoue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Murine Epsins Play an Integral Role in Podocyte Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2020050691"}], "href": "https://doi.org/10.1681/ASN.2020050691"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33051360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33051360"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yang Mao, Xiao Qiong Liu, Yu Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fibroblast growth factor-2/platelet-derived growth factor enhances atherosclerotic plaque stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.14850"}], "href": "https://doi.org/10.1111/jcmm.14850"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31755222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31755222"}]}]}]}
Synonyms	EHB21
Proteins	EPN2_HUMAN
NCBI Gene ID	22905
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EPN2 has 7,235 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 128 datasets.

Click the + buttons to view associations for EPN2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EPN2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of EPN2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of EPN2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of EPN2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of EPN2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of EPN2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of EPN2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of EPN2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of EPN2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of EPN2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of EPN2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EPN2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of EPN2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EPN2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EPN2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EPN2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EPN2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of EPN2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EPN2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EPN2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EPN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EPN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EPN2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing EPN2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EPN2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with EPN2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of EPN2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EPN2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EPN2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EPN2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EPN2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with EPN2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with EPN2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with EPN2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EPN2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at EPN2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EPN2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EPN2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing EPN2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with EPN2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with EPN2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.