MAP4K3 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase kinase kinase kinase 3
Description	This gene encodes a member of the mitogen-activated protein kinase kinase kinase kinase family. The encoded protein activates key effectors in cell signalling, among them c-Jun. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAP4K3 (also known as GLK) is a Ste20 family serine/threonine kinase that plays a critical role in coupling amino acid availability to the activation of the mTORC1 signaling pathway. Early studies demonstrated that MAP4K3 is required for maximal phosphorylation of downstream mTORC1 substrates such as S6 kinase and 4E‐BP1 in both Drosophila and mammalian cells under amino acid–rich conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, its kinase activity is tightly regulated by nutrient levels: MAP4K3 undergoes an essential autophosphorylation event at Ser170, which is reversed by PP2A in complex with a targeting subunit (PR61 ε) upon amino acid withdrawal, thus modulating mTORC1 signaling according to cellular metabolic status."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in nutrient sensing and growth regulation, MAP4K3 has been implicated in cancer cell behavior. In non‐small cell lung cancer, MAP4K3 is directly repressed by microRNA let‑7c, and its downregulation correlates with reduced cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Conversely, overexpression of MAP4K3 promotes tumor metastasis through interaction with the scaffold protein IQGAP1, leading to enhanced phosphorylation events that drive cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight the multifaceted functions of MAP4K3 as an amino acid sensor that modulates mTORC1-mediated cell growth and as a regulator of tumor cell migration and metastasis. Its dynamic regulation by nutrient signals and microRNAs makes MAP4K3 a promising diagnostic biomarker and therapeutic target in diseases characterized by deregulated growth and metastasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Greg M Findlay, Lijun Yan, Julia Procter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20061881"}], "href": "https://doi.org/10.1042/BJ20061881"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17253963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17253963"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lijun Yan, Virginie Mieulet, Darren Burgess, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PP2A T61 epsilon is an inhibitor of MAP4K3 in nutrient signaling to mTOR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.01.031"}], "href": "https://doi.org/10.1016/j.molcel.2010.01.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20227368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20227368"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Bingtian Zhao, Haibo Han, Jinfeng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2013.08.030"}], "href": "https://doi.org/10.1016/j.canlet.2013.08.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23981581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23981581"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Huai-Chia Chuang, Chih-Chi Chang, Chiao-Fang Teng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-19-1402"}], "href": "https://doi.org/10.1158/0008-5472.CAN-19-1402"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31431460"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31431460"}]}]}]}
Synonyms	MEKKK3, RAB8IPL1, MAPKKKK3, MEKKK 3
Proteins	M4K3_HUMAN
NCBI Gene ID	8491
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAP4K3 has 6,949 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 124 datasets.

Click the + buttons to view associations for MAP4K3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAP4K3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by MAP4K3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MAP4K3 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 MAP4K3 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 MAP4K3 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 MAP4K3 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 MAP4K3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAP4K3 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP4K3 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 MAP4K3 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 MAP4K3 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 MAP4K3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP4K3 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 MAP4K3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAP4K3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAP4K3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAP4K3 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 MAP4K3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAP4K3 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 MAP4K3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing MAP4K3 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 MAP4K3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAP4K3 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 MAP4K3 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 MAP4K3 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 MAP4K3 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 MAP4K3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAP4K3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MAP4K3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MAP4K3 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 MAP4K3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MAP4K3 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 MAP4K3 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 MAP4K3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAP4K3 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 MAP4K3 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 MAP4K3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAP4K3 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 MAP4K3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with MAP4K3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with MAP4K3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.