TAOK3 Gene

Name	TAO kinase 3
Description	The protein encoded by this gene is a serine/threonine protein kinase that activates the p38/MAPK14 stress-activated MAPK cascade but inhibits the basal activity of the MAPK8/JNK cascade. The encoded protein is a member of the GCK subfamily of STE20-like kinases. [provided by RefSeq, Oct 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTAOK3 is a widely expressed serine/threonine kinase that critically regulates T cell receptor (TCR) signaling. In human T cells, TAOK3 prevents premature attenuation of TCR signaling by limiting the early engagement of the inhibitory phosphatase SHP-1 with LCK. This kinase phosphorylates SHP-1, thereby promoting its ubiquitylation and proteasomal degradation, which sustains IL-2 production and appropriate T cell activation thresholds. These findings underscore its central role in fine‐tuning both tonic and ligand‐dependent TCR signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immunomodulatory actions, TAOK3 functions as an upstream activator within the JNK cascade, as demonstrated in osteoblasts where its deficiency results in impaired differentiation and skeletal hypomineralization. In oncological studies, an overexpressed variant of TAOK3 (often denoted TAO3) drives tumor aggressiveness by promoting invadopodia formation through modulating endosomal trafficking of the scaffold protein TKS5α and phosphorylating substrates such as the dynein component LIC2. Moreover, genetic variations in TAOK3 have been linked to differences in opioid dosing requirements for cancer pain management, thereby connecting its kinase activity to clinical variability in treatment response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, epigenetic modifications of TAOK3 have been associated with metabolic and inflammatory conditions. Reduced methylation levels in TAOK3 are linked to a decreased risk of childhood obesity, pointing to its potential as a biomarker in metabolic dysregulation. Furthermore, emerging data indicate that TAOK3 influences immune cell functions relevant to allergic asthma by modulating key cellular responses in dendritic cells and lymphocytes, thus offering a novel target for tailored therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "João V S Ormonde, Zhigang Li, Camille Stegen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TAOK3 Regulates Canonical TCR Signaling by Preventing Early SHP-1-Mediated Inactivation of LCK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1800284"}], "href": "https://doi.org/10.4049/jimmunol.1800284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30373850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30373850"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexandre Poirier, João Vitor Silva Ormonde, Isabelle Aubry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The induction of SHP-1 degradation by TAOK3 ensures the responsiveness of T cells to TCR stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.adg4422"}], "href": "https://doi.org/10.1126/scisignal.adg4422"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38166031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38166031"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nuria Ruiz-Reig, Belen Andres, Thomas Lamonerie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Struct Funct (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00429-018-1687-0"}], "href": "https://doi.org/10.1007/s00429-018-1687-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29869132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29869132"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Timothy Gutteridge, Mahalakshmi Kumaran, Sunita Ghosh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pain Symptom Manage (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jpainsymman.2018.07.011"}], "href": "https://doi.org/10.1016/j.jpainsymman.2018.07.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30031856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30031856"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shinji Iizuka, Manuela Quintavalle, Jose C Navarro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine-Threonine Kinase TAO3-Mediated Trafficking of Endosomes Containing the Invadopodia Scaffold TKS5α Promotes Cancer Invasion and Tumor Growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-20-2383"}], "href": "https://doi.org/10.1158/0008-5472.CAN-20-2383"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33414172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33414172"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mingchuang Sun, Zhaoxing Li, Xiaoyuan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TAOK3 Facilitates Esophageal Squamous Cell Carcinoma Progression and Cisplatin Resistance Through Augmenting Autophagy Mediated by IRGM."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Sci (Weinh) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/advs.202300864"}], "href": "https://doi.org/10.1002/advs.202300864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37705061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37705061"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "R C Huang, E S Garratt, H Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15592294.2015.1080411"}], "href": "https://doi.org/10.1080/15592294.2015.1080411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26646899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26646899"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bastiaan Maes, Ursula Smole, Matthias Vanderkerken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The STE20 kinase TAOK3 controls the development of house dust mite-induced asthma in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2021.08.020"}], "href": "https://doi.org/10.1016/j.jaci.2021.08.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34506849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34506849"}]}]}]}
Synonyms	JIK, MAP3K18, hKFC-A
Proteins	TAOK3_HUMAN
NCBI Gene ID	51347
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TAOK3 has 8,461 functional associations with biological entities spanning 8 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) extracted from 131 datasets.

Click the + buttons to view associations for TAOK3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TAOK3 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 TAOK3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with TAOK3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TAOK3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TAOK3 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 TAOK3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TAOK3 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 TAOK3 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 TAOK3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TAOK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TAOK3 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 TAOK3 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	cellular components co-occuring with TAOK3 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 TAOK3 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 TAOK3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TAOK3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TAOK3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TAOK3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TAOK3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 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 TAOK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TAOK3 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 TAOK3 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 TAOK3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TAOK3 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 TAOK3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TAOK3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.