MAPKAPK3 Gene

Name	mitogen-activated protein kinase-activated protein kinase 3
Description	This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMAPKAPK3 is a stress‐responsive serine/threonine kinase belonging to the p38 mitogen‐activated protein kinase (MAPK) pathway. In response to amino acid starvation, MAPKAPK3, together with its close homolog MK2, phosphorylates the essential autophagy regulator Beclin 1 at serine 90, an event required for the tumor suppressor activity of Beclin 1 and for the promotion of autophagy under nutrient stress conditions."}, {"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 viral infection, specifically hepatitis C virus (HCV), MAPKAPK3 has been identified as a direct binding partner of the viral core protein. This interaction enhances HCV IRES‐mediated translation, suggesting that HCV exploits MAPKAPK3 to facilitate its propagation by increasing the efficiency of viral protein synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMAPKAPK3 is uniquely activated by multiple upstream kinases including ERK, p38, and JNK in response to both mitogenic and stress‐inducing signals. Its dynamic subcellular localization—being actively exported to the cytoplasm following stimulation—points to mechanisms that allow cells to fine‐tune enzyme activity independently of activation status, thereby tailoring cellular responses to specific environmental cues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, MAPKAPK3 plays a role in inflammatory signaling. It is implicated in pathways leading to the production of pro‐inflammatory cytokines such as tumor necrosis factor alpha, and its detailed structural characterization has provided valuable insights for the development of selective anti‐inflammatory inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, the kinase is up‐regulated during ischemic preconditioning in the heart, indicating that enhanced MAPKAPK3 expression may contribute to the adaptive gene expression changes that protect myocardial tissue against ischemic injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCompelling evidence has also linked MAPKAPK3 to retinal physiology. A heterozygous, pathogenic mutation in MAPKAPK3 (p.Leu173Pro) was found to segregate with Martinique crinkled retinal pigment epitheliopathy, an inherited retinal dystrophy. The mutant protein displays abnormal cytoplasmic localization causing cytoskeletal alterations and defective cell division, while murine models exhibit irregularities in Bruch’s membrane structure, underscoring the importance of MAPKAPK3 in maintaining retinal integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, studies in human fibroblasts and cancer cell models indicate that MAPKAPK3 plays a context‐dependent role in cell proliferation and replicative lifespan. Both overexpression and depletion of MAPKAPK3 can induce a proliferative arrest associated with senescence, partly through its interaction with Polycomb Repressive Complex 1 (PRC1) and subsequent deregulation of cell cycle inhibitors. In cancer cells, loss of MAPKAPK3 function correlates with enhanced proliferation, emphasizing its nuanced role in growth control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yongjie Wei, Zhenyi An, Zhongju Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.05289"}], "href": "https://doi.org/10.7554/eLife.05289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25693418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25693418"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Huong T T Ngo, Long V Pham, Jong-Wook Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of mitogen-activated protein kinase-activated protein kinase 3 by hepatitis C virus core protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.03353-12"}], "href": "https://doi.org/10.1128/JVI.03353-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23487458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23487458"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Vera Zakowski, Georgios Keramas, Karin Kilian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitogen-activated 3p kinase is active in the nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2004.05.027"}], "href": "https://doi.org/10.1016/j.yexcr.2004.05.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15302577"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15302577"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Robert Cheng, Brunella Felicetti, Shilpa Palan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.294"}], "href": "https://doi.org/10.1002/pro.294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19937655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19937655"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Boris Z Simkhovich, Serge Abdishoo, Coralie Poizat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene activity changes in ischemically preconditioned rabbit heart gene: discovery array study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Heart Dis (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00132580-200203000-00002"}], "href": "https://doi.org/10.1097/00132580-200203000-00002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11975836"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11975836"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Isabelle Meunier, Guy Lenaers, Béatrice Bocquet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv624"}], "href": "https://doi.org/10.1093/hmg/ddv624"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26744326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26744326"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Albert Jean-Charles, Harold Merle, Isabelle Audo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ophtha.2016.06.028"}], "href": "https://doi.org/10.1016/j.ophtha.2016.06.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27474146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27474146"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Peggy Prickaerts, Hanneke E C Niessen, Vivian E H Dahlmans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MK3 modulation affects BMI1-dependent and independent cell cycle check-points."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0118840"}], "href": "https://doi.org/10.1371/journal.pone.0118840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25853770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25853770"}]}]}]}
Synonyms	3PK, MAPKAP-K3, MDPT3, MAPKAPK-3, MAPKAP3, MK-3
Proteins	MAPK3_HUMAN
NCBI Gene ID	7867
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAPKAPK3 has 7,783 functional associations with biological entities spanning 9 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, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for MAPKAPK3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAPKAPK3 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAPKAPK3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAPKAPK3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAPKAPK3 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 MAPKAPK3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAPKAPK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAPKAPK3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAPKAPK3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAPKAPK3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 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 MAPKAPK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAPKAPK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for MAPKAPK3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MAPKAPK3 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 MAPKAPK3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAPKAPK3 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 MAPKAPK3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with MAPKAPK3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with MAPKAPK3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of MAPKAPK3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.