| Name | GCN1 activator of EIF2AK4 |
| Description | Enables several functions, including protein kinase regulator activity; stalled ribosome sensor activity; and ubiquitin-protein transferase regulator activity. Involved in protein-RNA covalent cross-linking repair. Located in cytosol. Is active in cytosolic ribosome. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GCN1 is an evolutionarily conserved ribosome‐binding protein that plays a critical role in activating the eIF2α kinase GCN2 in response to diverse cellular stresses—most notably amino acid starvation. By binding to ribosomes and delivering uncharged tRNAs from stalled translation complexes to GCN2, GCN1 facilitates eIF2α phosphorylation, which in turn dampens global protein synthesis while selectively upregulating stress‐responsive genes. This mechanism underpins the integrated stress response and extends to additional processes such as nutrient sensing, cell cycle regulation, and the modulation of oxidative and proteotoxic stress. Interactions with regulatory proteins like IMPACT further fine‐tune the level of GCN2 activation, affecting neuronal function, metabolic adaptation, antiviral defense, and even cancer cell growth. Structural studies of the GCN2–GCN1 interface have begun to reveal important binding domains that are essential for this activation step, underscoring the potential of targeting this axis therapeutically in varied disease contexts. Collectively, investigations in yeast and mammalian systems highlight the indispensable function of GCN1 in coupling ribosome‐associated translational control to cellular stress signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alison J Inglis, Glenn R Masson, Sichen Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of GCN2 by the ribosomal P-stalk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1813352116"}], "href": "https://doi.org/10.1073/pnas.1813352116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30804176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30804176"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tavane D Cambiaghi, Catia M Pereira, Renuka Shanmugam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evolutionarily conserved IMPACT impairs various stress responses that require GCN1 for activating the eIF2 kinase GCN2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.12.021"}], "href": "https://doi.org/10.1016/j.bbrc.2013.12.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24333428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24333428"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cátia M Pereira, Evelyn Sattlegger, Hao-Yuan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M408571200"}], "href": "https://doi.org/10.1074/jbc.M408571200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15937339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15937339"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Richard C Silva, Evelyn Sattlegger, Beatriz A Castilho "}, {"type": "b", "children": [{"type": "t", "text": "Perturbations in actin dynamics reconfigure protein complexes that modulate GCN2 activity and promote an eIF2 response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.194738"}], "href": "https://doi.org/10.1242/jcs.194738"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27852836"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27852836"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yoshitaka Hirohata, Akihisa Kato, Masaaki Oyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactome analysis of herpes simplex virus 1 envelope glycoprotein H."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microbiol Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1348-0421.12255"}], "href": "https://doi.org/10.1111/1348-0421.12255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25808324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25808324"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elena Harjes, Geoffrey B Jameson, Yi-Hsuan Tu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Experimentally based structural model of Yih1 provides insight into its function in controlling the key translational regulator Gcn2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.13990"}], "href": "https://doi.org/10.1002/1873-3468.13990"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33156522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33156522"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Madison Furnish, Dillon P Boulton, Victoria Genther, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MIRO2 Regulates Prostate Cancer Cell Growth via GCN1-Dependent Stress Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-21-0374"}], "href": "https://doi.org/10.1158/1541-7786.MCR-21-0374"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34992146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34992146"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Su Jung Lee, Mark J Swanson, Evelyn Sattlegger "}, {"type": "b", "children": [{"type": "t", "text": "Gcn1 contacts the small ribosomal protein Rps10, which is required for full activation of the protein kinase Gcn2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20140782"}], "href": "https://doi.org/10.1042/BJ20140782"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25437641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25437641"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "H Kubota, Y Sakaki, T Ito "}, {"type": "b", "children": [{"type": "t", "text": "GI domain-mediated association of the eukaryotic initiation factor 2alpha kinase GCN2 with its activator GCN1 is required for general amino acid control in budding yeast."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C000262200"}], "href": "https://doi.org/10.1074/jbc.C000262200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10801780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10801780"}]}]}]}
|
| NCBI Gene ID | 10985 |
| API | |
| Download Associations | |
| Predicted Functions |
 |
| Co-expressed Genes |
|
| Expression in Tissues and Cell Lines |
|
GCN1 has 2,381 functional associations with biological entities spanning 5 categories (chemical, functional term, phrase or reference, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA) extracted from 41 datasets.
Click the + buttons to view associations for GCN1 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 GCN1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of GCN1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Proteomics | Cell lines associated with GCN1 protein from the CCLE Cell Line Proteomics dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of GCN1 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 GCN1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CM4AI U2OS Cell Map Protein Localization Assemblies | assemblies containing GCN1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing GCN1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 | cellular components containing GCN1 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 GCN1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by GCN1 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 GCN1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with GCN1 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 GCN1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving GCN1 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving GCN1 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing GCN1 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing GCN1 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by GCN1 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by GCN1 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of GCN1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with GCN1 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by GCN1 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of GCN1 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 GCN1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of GCN1 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of GCN1 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by GCN1 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of GCN1 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving GCN1 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving GCN1 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2024 | pathways involving GCN1 protein from the Reactome Pathways 2024 dataset. | |
| Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of GCN1 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of GCN1 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of GCN1 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of GCN1 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of GCN1 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sci-Plex Drug Perturbation Signatures | drug perturbations changing expression of GCN1 gene from the Sci-Plex Drug Perturbation Signatures dataset. | |
| Tahoe Therapeutics Tahoe 100M Perturbation Atlas | drug perturbations changing expression of GCN1 gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of GCN1 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of GCN1 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with GCN1 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
