EPN1 Gene

Name	epsin 1
Description	This gene encodes a member of the epsin protein family. The encoded protein binds clathrin and is involved in the endocytosis of clathrin-coated vesicles. Loss of function of this gene is associated with reduced tumor growth and progression in certain cancer types. [provided by RefSeq, Mar 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Epsin1 (EPN1) is a multifunctional, ubiquitin‐binding endocytic adaptor that plays several central roles in clathrin‐mediated endocytosis. Through its ENTH domain, EPN1 binds phosphatidylinositol‐4,5‐bisphosphate in the plasma membrane and, upon formation of an amphipathic α–helix, directly induces membrane curvature to promote the invagination and budding of clathrin‐coated pits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Its tandem ubiquitin‐interacting motifs (UIMs) confer the ability to selectively recognize and bind ubiquitinated cargo, which is critical for the efficient internalization of activated receptors such as the epidermal growth factor receptor (EGFR) and protease‐activated receptor-1 (PAR1)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n In addition, epsin1 contributes to endocytosis even when cryptic ubiquitination sites are engaged for EGFR internalization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its direct role in membrane remodeling and cargo selection, EPN1 functions in regulating receptor signaling. Genetic studies demonstrate that epsin1, along with its isoforms, is critical for the specialized internalization processes that underpin Notch activation during development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, epsin1 in vascular endothelial cells helps modulate receptor turnover by mediating the internalization and degradation of receptors such as VEGFR2 and VEGFR3, processes that are essential for proper angiogenesis and lymphatic valve formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Epsin1 also plays a key role in the dynamics of coat assembly. In epsin-deficient cells, impaired coupling between the clathrin coat and the actin cytoskeleton leads to defects in vesicle invagination, cell division, and even mitotic spindle integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, epsin1 is implicated in the endocytosis of additional receptors such as the erythropoietin receptor (EpoR), where it bridges ubiquitination events with adaptor protein interactions to drive receptor internalization and attenuate signaling output."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore that epsin1 functions as a critical coordinator of membrane remodeling, cargo recognition through ubiquitin binding, and signal regulation via endocytic receptor turnover.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marijn G J Ford, Ian G Mills, Brian J Peter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Curvature of clathrin-coated pits driven by epsin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01020"}], "href": "https://doi.org/10.1038/nature01020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12353027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12353027"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David J Busch, Justin R Houser, Carl C Hayden, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intrinsically disordered proteins drive membrane curvature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms8875"}], "href": "https://doi.org/10.1038/ncomms8875"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26204806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26204806"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yusuke Sato, Azusa Yoshikawa, Hisatoshi Mimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.160"}], "href": "https://doi.org/10.1038/emboj.2009.160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19536136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19536136"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maja Kazazic, Vibeke Bertelsen, Ketil Winther Pedersen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epsin 1 is involved in recruitment of ubiquitinated EGF receptors into clathrin-coated pits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2008.00858.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2008.00858.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19054389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19054389"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Buxin Chen, Michael R Dores, Neil Grimsey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adaptor protein complex-2 (AP-2) and epsin-1 mediate protease-activated receptor-1 internalization via phosphorylation- and ubiquitination-dependent sorting signals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.299776"}], "href": "https://doi.org/10.1074/jbc.M111.299776"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21965661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21965661"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Arola Fortian, Lai K Dionne, Sun H Hong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endocytosis of Ubiquitylation-Deficient EGFR Mutants via Clathrin-Coated Pits is Mediated by Ubiquitylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tra.12314"}], "href": "https://doi.org/10.1111/tra.12314"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26251007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26251007"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hong Chen, Genevieve Ko, Alessandra Zatti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0907008106"}], "href": "https://doi.org/10.1073/pnas.0907008106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19666558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19666558"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Satish Pasula, Xiaofeng Cai, Yunzhou Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI64537"}], "href": "https://doi.org/10.1172/JCI64537"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23187125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23187125"}]}, {"type": "r", "ref": 9, "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": 10, "children": [{"type": "t", "text": "Kandice L Tessneer, Satish Pasula, Xiaofeng Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic reduction of vascular endothelial growth factor receptor 2 rescues aberrant angiogenesis caused by epsin deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.113.302586"}], "href": "https://doi.org/10.1161/ATVBAHA.113.302586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24311377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24311377"}]}, {"type": "r", "ref": 11, "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": 12, "children": [{"type": "t", "text": "Zhonghua Liu, Yixian Zheng "}, {"type": "b", "children": [{"type": "t", "text": "A requirement for epsin in mitotic membrane and spindle organization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200902071"}], "href": "https://doi.org/10.1083/jcb.200902071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19704019"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19704019"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Gamze B Bulut, Rita Sulahian, Huiyu Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cbl ubiquitination of p85 is essential for Epo-induced EpoR endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2013-05-506212"}], "href": "https://doi.org/10.1182/blood-2013-05-506212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24113870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24113870"}]}]}]}
Proteins	EPN1_HUMAN
NCBI Gene ID	29924
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EPN1 has 6,323 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 125 datasets.

Click the + buttons to view associations for EPN1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EPN1 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 EPN1 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 EPN1 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 EPN1 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 EPN1 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 EPN1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving EPN1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of EPN1 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 EPN1 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 EPN1 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 EPN1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EPN1 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 EPN1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EPN1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EPN1 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 EPN1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EPN1 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 EPN1 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 EPN1 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 EPN1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EPN1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EPN1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing EPN1 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 EPN1 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 EPN1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing EPN1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of EPN1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EPN1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EPN1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EPN1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of EPN1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EPN1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EPN1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with EPN1 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 EPN1 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 EPN1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DrugBank Drug Targets	interacting drugs for EPN1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at EPN1 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 EPN1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EPN1 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 EPN1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.