UPF2 Gene

Name	UPF2 regulator of nonsense transcripts homolog (yeast)
Description	This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUPF2 functions as a central scaffolding and regulatory factor in the nonsense‐mediated mRNA decay (NMD) pathway. It serves as an essential bridge between components bound by the exon–junction complex (via UPF3) and the RNA helicase UPF1. Binding of UPF2 to UPF1 induces a defined conformational change that transforms UPF1 from an RNA‐clamping state into an active, ATP-dependent RNA-unwinding mode. Consequently, UPF2 and UPF3 cooperatively stimulate UPF1’s catalytic activities, which are crucial for efficient degradation of transcripts containing premature termination codons."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in activating UPF1, UPF2 participates in the assembly and dynamic regulation of multiple NMD complexes. Structural studies have revealed that UPF2 engages UPF3 via its middle domains while simultaneously interacting with the regulatory region of UPF1. This bipartite binding mode not only fine-tunes UPF1’s association with RNA but also facilitates interactions with additional factors such as eRF3, thereby integrating UPF2 into the formation of the SURF complex and promoting UPF1 phosphorylation. These coordinated interactions promote proper spatial coupling between a stalled ribosome and the exon–junction complex."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeficiencies or dysregulation of UPF2 impair NMD activity, leading to reduced UPF1 phosphorylation and the ensuing stabilization of aberrant mRNAs. UPF2’s role as an adaptor extends to its interaction with components of the ubiquitin–proteasome system as well as factors involved in translation termination, ensuring tight regulation of NMD factor turnover. Perturbation of UPF2-dependent processes has been associated with cellular dysfunction and even neurodevelopmental anomalies, highlighting the broader biological importance of UPF2-mediated NMD in maintaining transcriptome integrity and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jan Kadlec, Elisa Izaurralde, Stephen Cusack "}, {"type": "b", "children": [{"type": "t", "text": "The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb741"}], "href": "https://doi.org/10.1038/nsmb741"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15004547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15004547"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nao Hosoda, Yoon Ki Kim, Fabrice Lejeune, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb995"}], "href": "https://doi.org/10.1038/nsmb995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16186820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16186820"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hala Chamieh, Lionel Ballut, Fabien Bonneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb1330"}], "href": "https://doi.org/10.1038/nsmb1330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18066079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18066079"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marcello Clerici, André Mourão, Irina Gutsche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2."}]}, {"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.2009.175"}], "href": "https://doi.org/10.1038/emboj.2009.175"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19556969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19556969"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sutapa Chakrabarti, Uma Jayachandran, Fabien Bonneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2011.02.010"}], "href": "https://doi.org/10.1016/j.molcel.2011.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21419344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21419344"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marcello Clerici, Aurélien Deniaud, Volker Boehm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkt1197"}], "href": "https://doi.org/10.1093/nar/gkt1197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24271394"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24271394"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Roberto Melero, Akiko Uchiyama, Raquel Castaño, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2014.05.015"}], "href": "https://doi.org/10.1016/j.str.2014.05.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25002321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25002321"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jürgen Wittmann, Elly M Hol, Hans-Martin Jäck "}, {"type": "b", "children": [{"type": "t", "text": "hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.4.1272-1287.2006"}], "href": "https://doi.org/10.1128/MCB.26.4.1272-1287.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16449641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16449641"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Guramrit Singh, Steffen Jakob, Mark G Kleedehn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Communication with the exon-junction complex and activation of nonsense-mediated decay by human Upf proteins occur in the cytoplasm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.06.030"}], "href": "https://doi.org/10.1016/j.molcel.2007.06.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17803942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17803942"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xia Zhao, Atsushi Nogawa, Tsukasa Matsunaga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteasome inhibitors and knockdown of SMG1 cause accumulation of Upf1 and Upf2 in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2013.2149"}], "href": "https://doi.org/10.3892/ijo.2013.2149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24173962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24173962"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Andrés López-Perrote, Raquel Castaño, Roberto Melero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkv1527"}], "href": "https://doi.org/10.1093/nar/gkv1527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26740584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26740584"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jennifer L Johnson, Loredana Stoica, Yuwei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2019.08.027"}], "href": "https://doi.org/10.1016/j.neuron.2019.08.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31585809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31585809"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Guangpu Xue, Vincent D Maciej, Alexandrina Machado de Amorim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of RNA-binding properties of the RNA helicase UPF1 by its activator UPF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.079188.122"}], "href": "https://doi.org/10.1261/rna.079188.122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36456182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36456182"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Lukas M Langer, Katharina Kurscheidt, Jérôme Basquin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkae323"}], "href": "https://doi.org/10.1093/nar/gkae323"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38709891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38709891"}]}]}]}
Synonyms	HUPF2, RENT2, SMG-3
Proteins	RENT2_HUMAN
NCBI Gene ID	26019
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UPF2 has 6,446 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 117 datasets.

Click the + buttons to view associations for UPF2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UPF2 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 UPF2 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 UPF2 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 UPF2 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 UPF2 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 UPF2 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 UPF2 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 UPF2 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 UPF2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UPF2 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 UPF2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UPF2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with UPF2 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 UPF2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UPF2 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 UPF2 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 UPF2 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 UPF2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UPF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UPF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with UPF2 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 UPF2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing UPF2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of UPF2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UPF2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with UPF2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with UPF2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with UPF2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with UPF2 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 UPF2 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 UPF2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UPF2 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 UPF2 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 UPF2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UPF2 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 UPF2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with UPF2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with UPF2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of UPF2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UPF2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing UPF2 from the GeneSigDB Published Gene Signatures dataset.