UBR4 Gene

HGNC Family	Ubiquitin protein ligase E3 component n-recognins (UBR)
Name	ubiquitin protein ligase E3 component n-recognin 4
Description	The protein encoded by this gene is an E3 ubiquitin-protein ligase that interacts with the retinoblastoma-associated protein in the nucleus and with calcium-bound calmodulin in the cytoplasm. The encoded protein appears to be a cytoskeletal component in the cytoplasm and part of the chromatin scaffold in the nucleus. In addition, this protein is a target of the human papillomavirus type 16 E7 oncoprotein. [provided by RefSeq, Aug 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUBR4, also known as p600, is exploited by diverse viruses to subvert host immune responses. In dengue virus infection, UBR4 preferentially binds to the proteolytically processed NS5 protein, bridging STAT2 and facilitating its proteasome‐dependent degradation, which is critical for antagonizing type I interferon signaling and enabling efficient viral replication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, the human papillomavirus type 16 E7 oncoprotein targets UBR4 to promote cellular transformation independent of classical retinoblastoma protein pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and Rift Valley fever virus engages UBR4 via its glycoprotein Gn to support viral RNA production and high viral titers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond viral interactions, UBR4 plays key roles in maintaining cellular architecture and protein homeostasis. As p600, it functions as a chromatin scaffold in the nucleus in concert with the retinoblastoma protein and participates in the cytoplasmic organization by forming a meshwork with clathrin that is essential for integrin-mediated membrane dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In renal podocytes, UBR4 regulates the stability of podocin, ensuring proper function of the glomerular filtration barrier."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, UBR4 associates with Ca2+-bound calmodulin at maturing endosomes, a localization that is essential for early endosome biogenesis and subsequent cargo trafficking."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, UBR4 forms part of an E2–E3 complex with RAD6 and KCMF1 that targets substrates for lysosome-mediated degradation, and it participates in the endoplasmic reticulum-associated degradation of misfolded antibody heavy chains, with implications for improved antibody production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, UBR4 is critical for proper neuronal development and function. Mutations in UBR4 have been linked to episodic ataxia, likely through its involvement in calcium signaling and interactions with proteins such as calmodulin and ITPR1 that are vital for presynaptic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " More broadly, UBR4 has been implicated in neurogenesis, neuronal migration, and survival, underscoring its multifunctional role in the central nervous system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, deletions encompassing UBR4 have been associated with a novel contiguous gene deletion syndrome characterized by intellectual and developmental deficits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLastly, UBR4 influences immune cell regulation. Specific variants of UBR4 impair the lysosomal degradation of the phosphatase CD45, leading to accumulation of this key regulator on T cells and lowering the threshold for T cell activation. In the presence of elevated levels of the kinase FYN, this mechanism contributes to Th2 polarization and may play a role in the pathogenesis of IgG4-related disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Juliet Morrison, Maudry Laurent-Rolle, Ana M Maestre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1003265"}], "href": "https://doi.org/10.1371/journal.ppat.1003265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23555265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23555265"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kyung-Won Huh, Joseph DeMasi, Hidesato Ogawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0505337102"}], "href": "https://doi.org/10.1073/pnas.0505337102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16061792"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16061792"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nicole Bracci, Cynthia de la Fuente, Sahar Saleem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rift Valley fever virus Gn V5-epitope tagged virus enables identification of UBR4 as a Gn interacting protein that facilitates Rift Valley fever virus production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virology (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.virol.2021.12.010"}], "href": "https://doi.org/10.1016/j.virol.2021.12.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35032865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35032865"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yoshihiro Nakatani, Hiroaki Konishi, Alex Vassilev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p600, a unique protein required for membrane morphogenesis and cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0507458102"}], "href": "https://doi.org/10.1073/pnas.0507458102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16214886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16214886"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Judith Conroy, Paul McGettigan, Raymond Murphy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel locus for episodic ataxia:UBR4 the likely candidate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2013.173"}], "href": "https://doi.org/10.1038/ejhg.2013.173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23982692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23982692"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sung Tae Kim, Yoon Jee Lee, Takafumi Tasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The N-recognin UBR4 of the N-end rule pathway is targeted to and required for the biogenesis of the early endosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.217646"}], "href": "https://doi.org/10.1242/jcs.217646"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30111582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30111582"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jenny H Hong, Lilia Kaustov, Etienne Coyaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KCMF1 (potassium channel modulatory factor 1) Links RAD6 to UBR4 (ubiquitin N-recognin domain-containing E3 ligase 4) and lysosome-mediated degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M114.042168"}], "href": "https://doi.org/10.1074/mcp.M114.042168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25582440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25582440"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Danming Tang, Wendy Sandoval, Cynthia Lam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBR E3 ligases and the PDIA3 protease control degradation of unfolded antibody heavy chain by ERAD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201908087"}], "href": "https://doi.org/10.1083/jcb.201908087"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32558906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32558906"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kwang-Dong Choi, Ji-Soo Kim, Hyo-Jung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Variants Associated with Episodic Ataxia in Korea."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-14254-7"}], "href": "https://doi.org/10.1038/s41598-017-14254-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29062094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29062094"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kari Parsons, Yoshihiro Nakatani, Minh Dang Nguyen "}, {"type": "b", "children": [{"type": "t", "text": "p600/UBR4 in the central nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-014-1788-8"}], "href": "https://doi.org/10.1007/s00018-014-1788-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25424645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25424645"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Line Aagaard Nolting, Charlotte Brasch-Andersen, Helen Cox, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new 1p36.13-1p36.12 microdeletion syndrome characterized by learning disability, behavioral abnormalities, and ptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13739"}], "href": "https://doi.org/10.1111/cge.13739"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32170730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32170730"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Qingxiang Liu, Yanyan Zheng, Ines Sturmlechner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IKZF1 and UBR4 gene variants drive autoimmunity and Th2 polarization in IgG4-related disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI178692"}], "href": "https://doi.org/10.1172/JCI178692"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38885295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38885295"}]}]}]}
Synonyms	ZUBR1, RBAF600
Proteins	UBR4_HUMAN
NCBI Gene ID	23352
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UBR4 has 9,780 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 129 datasets.

Click the + buttons to view associations for UBR4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UBR4 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 UBR4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UBR4 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of UBR4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UBR4 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 UBR4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with UBR4 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of UBR4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UBR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UBR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing UBR4 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 UBR4 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 UBR4 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 UBR4 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 UBR4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UBR4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with UBR4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of UBR4 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with UBR4 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 UBR4 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 UBR4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UBR4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for UBR4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at UBR4 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 UBR4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UBR4 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 UBR4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with UBR4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of UBR4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UBR4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.