UBA7 Gene

HGNC Family	Ubiquitin-like activating enzymes (UBA)
Name	ubiquitin-like modifier activating enzyme 7
Description	The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme is a retinoid target that triggers promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) degradation and apoptosis in acute promyelocytic leukemia, where it is involved in the conjugation of the ubiquitin-like interferon-stimulated gene 15 protein. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUBA7 (also known as UBE1L) functions as the E1 activating enzyme for ISG15, a ubiquitin-like protein whose conjugation (ISGylation) plays a pivotal role in regulating oncogenic and antiviral signaling. In acute promyelocytic leukemia (APL), retinoic acid rapidly induces UBA7 expression, which in turn promotes the ISG15 conjugation of key oncogenic targets such as the PML/RARα fusion protein. This modification facilitates proteasome-dependent degradation of PML/RARα, thereby triggering differentiation and apoptosis in RA-sensitive leukemic cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed biochemical analyses have revealed that UBA7 selectively activates its cognate E2 enzyme (UbcH8) to enable efficient ISG15 transfer, with distinct structural determinants in UbcH8 governing this specificity. In lung cancer models, UBA7-mediated ISGylation preferentially targets cyclin D1 for conjugation with ISG15, leading to reduced cyclin D1 protein stability and consequent growth inhibition, highlighting its potential antitumor role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the importance of UBA7 in the ISG15 system is underscored by findings in the context of viral infection and inflammatory signaling. Viral proteins, such as the HCMV-encoded pUL50, promote proteasomal degradation of UBA7, thereby subverting ISGylation and aiding viral evasion. In parallel, inflammatory cytokines like TNF-α can up-regulate components of the ISG15 machinery—including UBA7—via MAPK pathways, reinforcing its role in innate immune defense."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, recent work in breast cancer models has identified UBA7 as a bona fide tumor suppressor. UBA7-mediated ISGylation facilitates the clustering and nuclear relocalization of transcription factors such as STAT1 and STAT2 within promyelocytic leukemia bodies. This reorganization promotes the expression of chemokine-receptor ligands that attract cytotoxic T cells, thereby orchestrating an antitumor microenvironment and suppressing both primary tumor growth and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBE1L is a retinoid target that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.052011299"}], "href": "https://doi.org/10.1073/pnas.052011299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11891284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11891284"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ian Pitha-Rowe, Bret A Hassel, Ethan Dmitrovsky "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of UBE1L in ISG15 conjugation during retinoid-induced differentiation of acute promyelocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M309259200"}], "href": "https://doi.org/10.1074/jbc.M309259200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14976209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14976209"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Larissa A Durfee, Melissa L Kelley, Jon M Huibregtse "}, {"type": "b", "children": [{"type": "t", "text": "The basis for selective E1-E2 interactions in the ISG15 conjugation system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M804069200"}], "href": "https://doi.org/10.1074/jbc.M804069200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18583345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18583345"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qing Feng, David Sekula, Yongli Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBE1L causes lung cancer growth suppression by targeting cyclin D1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-08-0753"}], "href": "https://doi.org/10.1158/1535-7163.MCT-08-0753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19074853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19074853"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Myoung Kyu Lee, Ye Ji Kim, Young-Eui Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transmembrane Protein pUL50 of Human Cytomegalovirus Inhibits ISGylation by Downregulating UBE1L."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00462-18"}], "href": "https://doi.org/10.1128/JVI.00462-18"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29743376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29743376"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wannee Lertsooksawat, Ariyaphong Wongnoppavich, Kongthawat Chairatvit "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of interferon-stimulated gene 15 and its conjugation machinery, UbE1L and UbcH8 expression by tumor necrosis factor-α through p38 MAPK and JNK signaling pathways in human lung carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-019-03609-5"}], "href": "https://doi.org/10.1007/s11010-019-03609-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31428903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31428903"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jun-Bao Fan, Sayuri Miyauchi, Hui-Zhong Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell-Mediated Tumor Killing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-19-0608"}], "href": "https://doi.org/10.1158/2159-8290.CD-19-0608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31974171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31974171"}]}]}]}
Synonyms	UBE2, D8, UBA1B, UBE1L
Proteins	UBA7_HUMAN
NCBI Gene ID	7318
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UBA7 has 5,627 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 115 datasets.

Click the + buttons to view associations for UBA7 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UBA7 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 UBA7 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UBA7 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with UBA7 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 UBA7 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UBA7 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 UBA7 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of UBA7 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UBA7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing UBA7 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with UBA7 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 UBA7 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 UBA7 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UBA7 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with UBA7 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with UBA7 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by UBA7 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 UBA7 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 UBA7 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 UBA7 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 UBA7 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UBA7 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 UBA7 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 UBA7 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UBA7 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 UBA7 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with UBA7 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 UBA7 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UBA7 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 UBA7 from the GeneSigDB Published Gene Signatures dataset.