UFL1 Gene

Name	UFM1-specific ligase 1
Description	Enables UFM1 ligase activity and protein kinase binding activity. Involved in several processes, including positive regulation of reticulophagy; regulation of intracellular signal transduction; and regulation of primary metabolic process. Acts upstream of or within several processes, including positive regulation of cell population proliferation; regulation of proteasomal ubiquitin-dependent protein catabolic process; and response to endoplasmic reticulum stress. Located in cytoplasm; nucleus; and site of double-strand break. Part of protein-containing complex. Is active in endoplasmic reticulum membrane and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUFL1 functions as the E3 ligase in the ufmylation system to maintain genomic integrity by regulating the DNA damage response. Upon DNA damage, UFL1 is recruited to double‐strand breaks via the MRE11/RAD50/NBS1 complex where it catalyzes the monoufmylation of histone H4. This posttranslational modification facilitates the recruitment of chromatin modifiers, such as Suv39h1 and Tip60, thereby amplifying ATM kinase activation in a positive feedback loop to ensure a robust repair response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of inflammatory joint disease, particularly osteoarthritis, UFL1 exhibits a protective role in chondrocytes. Its low expression under IL-1β stimulation is associated with decreased cell viability and increased production of inflammatory mediators and extracellular matrix–degrading enzymes. Ectopic expression of UFL1 mitigates these deleterious effects by inhibiting the activation of the NF-κB signaling pathway and suppressing the production of pro-inflammatory cytokines and catabolic enzymes, thereby suggesting a potential therapeutic target for osteoarthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUFL1 is also critical for the antiviral innate immune response. Following RNA virus infection, UFL1 is recruited to endoplasmic reticulum–mitochondrial contact sites where it associates with the membrane-targeting protein 14-3-3ε. This complex is essential for the efficient interaction between activated RIG-I and the adaptor protein MAVS, leading to robust induction of type I and III interferons. Ufmylation thus emerges as a key posttranslational modification that fine-tunes the RIG-I signaling cascade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, UFL1 plays a protective role in ovarian function. It has been implicated in combating chemotherapy-induced premature ovarian failure and in alleviating lipopolysaccharide-induced stress in ovarian granulosa-like cells. In these cells, elevated UFL1 levels counteract endoplasmic reticulum stress and apoptosis by modulating ferroptosis through the p53/SLC7A11 axis and autophagy. These findings underscore UFL1’s potential as a therapeutic target for preserving ovarian function in the face of various cellular stresses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bo Qin, Jia Yu, Somaira Nowsheen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UFL1 promotes histone H4 ufmylation and ATM activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-09175-0"}], "href": "https://doi.org/10.1038/s41467-019-09175-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30886146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30886146"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Guangjie Yang, Yongsheng Wang, You Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UFL1 attenuates IL-1β-induced inflammatory response in human osteoarthritis chondrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2020.106278"}], "href": "https://doi.org/10.1016/j.intimp.2020.106278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32050156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32050156"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daltry L Snider, Moonhee Park, Kristen A Murphy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signaling from the RNA sensor RIG-I is regulated by ufmylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2119531119"}], "href": "https://doi.org/10.1073/pnas.2119531119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35394863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35394863"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiangting Tang, Hao Dong, Zhi Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Biol Endocrinol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12958-022-00956-9"}], "href": "https://doi.org/10.1186/s12958-022-00956-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35610622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35610622"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jingyi Li, Xiangting Tang, Xueer Tu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UFL1 alleviates ER stress and apoptosis stimulated by LPS via blocking the ferroptosis pathway in human granulosa-like cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stress Chaperones (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12192-022-01284-y"}], "href": "https://doi.org/10.1007/s12192-022-01284-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35729487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35729487"}]}]}]}
Synonyms	NLBP, MAXER, KIAA0776
Proteins	UFL1_HUMAN
NCBI Gene ID	23376
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UFL1 has 6,383 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 116 datasets.

Click the + buttons to view associations for UFL1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UFL1 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 UFL1 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 UFL1 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 UFL1 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 UFL1 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 UFL1 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 UFL1 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 UFL1 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 UFL1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of UFL1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UFL1 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 UFL1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UFL1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with UFL1 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 UFL1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UFL1 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 UFL1 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 UFL1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing UFL1 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 UFL1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UFL1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UFL1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing UFL1 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 UFL1 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 2025	cellular components co-occuring with UFL1 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 UFL1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UFL1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with UFL1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with UFL1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by UFL1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving UFL1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with UFL1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with UFL1 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 UFL1 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 UFL1 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 UFL1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UFL1 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 UFL1 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 UFL1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UFL1 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 UFL1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.