| Name | DNA-damage inducible 1 homolog 1 (S. cerevisiae) |
| Description | Predicted to enable aspartic-type endopeptidase activity. Involved in several processes, including cellular response to hydroxyurea; regulation of DNA stability; and regulation of protein stability. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ddi1‐like proteins—including DDI1 and its homolog DDI2—are evolutionarily conserved factors that couple ubiquitin recognition with proteolytic processing. These proteins harbor a ubiquitin‐like (UBL) domain and a retroviral protease domain that together confer dual functions: (i) acting as ubiquitin shuttle factors to deliver polyubiquitylated substrates to the 26S proteasome and (ii) serving as endoproteases that specifically cleave highly polyubiquitylated proteins, a function exemplified by their role in processing the transcription factor NRF1. This dual activity is supported by structural and functional analyses showing that the Ddi1/DDI2 family not only binds ubiquitin and proteasomes but also requires an intact protease domain to promote substrate turnover and prevent the accumulation of ubiquitin conjugates."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to their proteostatic functions, Ddi1‐like proteins modulate key signaling pathways. In yeast, for example, Ddi1 interacts with regulatory proteins such as Pho81 and Rad23 to act as a negative regulator in the PHO pathway, thereby influencing acid phosphatase expression under phosphate-limited conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, post‐translational modifications of these factors—as seen with ubiquitination by UBE3A—link DDI1 function to neurodevelopmental processes, suggesting that aberrant regulation may contribute to disorders such as Angelman syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In pathogenic organisms like Toxoplasma gondii, loss of DDI1 function disrupts the proper targeting of virulence factors, thereby altering host–pathogen interactions and contributing to defects in DNA replication and intracellular signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted role of Ddi1-like proteins in ubiquitin-mediated protein turnover and cellular regulation; their capacity to function both as shuttle factors and as proteases is critical for maintaining proteostasis and modulating diverse signaling pathways in both normal cellular physiology and disease states.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Barbara Dirac-Svejstrup, Jane Walker, Peter Faull, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2020.05.035"}], "href": "https://doi.org/10.1016/j.molcel.2020.05.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32521225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32521225"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Monika Sivá, Michal Svoboda, Václav Veverka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep30443"}], "href": "https://doi.org/10.1038/srep30443"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27461074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27461074"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Galen Andrew Collins, Zhe Sha, Chueh-Ling Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian Ddi2 is a shuttling factor containing a retroviral protease domain that influences binding of ubiquitylated proteins and proteasomal degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2022.101875"}], "href": "https://doi.org/10.1016/j.jbc.2022.101875"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35358511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35358511"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Choowong Auesukaree, Ikutaro Fuchigami, Tomoyuki Homma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ddi1p and Rad23p play a cooperative role as negative regulators in the PHO pathway in Saccharomyces cerevisiae."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.11.044"}], "href": "https://doi.org/10.1016/j.bbrc.2007.11.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18035052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18035052"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "S M Shahjahan Miah, Amanda K Purdy, Nicholas B Rodin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitylation of an internalized killer cell Ig-like receptor by Triad3A disrupts sustained NF-κB signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1000112"}], "href": "https://doi.org/10.4049/jimmunol.1000112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21270397"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21270397"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Heng Zhang, Yangfei Xue, Xu Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toxoplasma gondii UBL-UBA shuttle proteins regulate several important cellular processes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202100662RR"}], "href": "https://doi.org/10.1096/fj.202100662RR"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34727385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34727385"}]}]}]}
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| Proteins | DDI1_HUMAN |
| NCBI Gene ID | 414301 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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DDI1 has 1,704 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 70 datasets.
Click the + buttons to view associations for DDI1 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of DDI1 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 DDI1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of DDI1 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 DDI1 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 DDI1 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 DDI1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of DDI1 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of DDI1 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 DDI1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of DDI1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with DDI1 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 DDI1 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 DDI1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with DDI1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by DDI1 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 DDI1 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 DDI1 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 DDI1 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 DDI1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at DDI1 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 DDI1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of DDI1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of DDI1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of DDI1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of DDI1 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of DDI1 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of DDI1 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of DDI1 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving DDI1 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving DDI1 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving DDI1 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by DDI1 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of DDI1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with DDI1 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with DDI1 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with DDI1 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of DDI1 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of DDI1 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPM Cell Type and Tissue Protein Expression Profiles | cell types and tissues with high or low expression of DDI1 protein relative to other cell types and tissues from the HPM Cell Type and Tissue Protein Expression Profiles dataset. | |
| Hub Proteins Protein-Protein Interactions | interacting hub proteins for DDI1 from the curated Hub Proteins Protein-Protein Interactions dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with DDI1 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for DDI1 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of DDI1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of DDI1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of DDI1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of DDI1 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of DDI1 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain DDI1 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of DDI1 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for DDI1 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of DDI1 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of DDI1 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving DDI1 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving DDI1 protein from the Wikipathways PFOCR 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of DDI1 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at DDI1 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of DDI1 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of DDI1 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of DDI1 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sanger Dependency Map Cancer Cell Line Proteomics | cell lines associated with DDI1 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of DDI1 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of DDI1 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of DDI1 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of DDI1 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of DDI1 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of DDI1 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of DDI1 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of DDI1 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with DDI1 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with DDI1 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
