DGKZ Gene

Name	diacylglycerol kinase, zeta
Description	The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It may attenuate protein kinase C activity by regulating diacylglycerol levels in intracellular signaling cascade and signal transduction. Alternative splicing occurs at this locus and multiple transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Diacylglycerol kinase ζ (DGKζ, also called DGKZ) is a pivotal enzyme that terminates diacylglycerol (DAG)‐dependent signaling by catalyzing its conversion into phosphatidic acid (PA). This lipid‐remodeling reaction serves as a central checkpoint in diverse cellular contexts. In T lymphocytes, DGKζ is rapidly recruited to the immunological synapse upon receptor engagement, where it limits local DAG accumulation and thereby dampens Ras/ERK and protein kinase C–dependent signals. Such regulation is critical for T cell activation and the proper development of regulatory T cells, while deletion of DGKζ enhances cytokine production and natural killer (NK) cell function, underscoring its role as a negative regulator of immune activation."}, {"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, DGKζ interacts via its C‐terminal PDZ–binding motif with Sorting Nexin 27 (SNX27), a key adaptor in endosomal recycling, to modulate the trafficking and surface expression of receptors in T cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Its subcellular localization and kinase activity are finely tuned by posttranslational modifications – for instance, phosphorylation by PKCα on its MARCKS domain attenuates DGKζ activity, thereby influencing the balance between DAG and PA and affecting cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond the immune system, DGKζ‐derived PA serves as an essential mediator in the activation of growth–regulatory pathways. Overexpression of DGKζ in HEK293 cells under serum–deprived conditions promotes mammalian target of rapamycin (mTOR)–dependent phosphorylation of p70S6 kinase, while in skeletal muscle DGKζ is necessary for mechanically induced PA production, mTOR pathway activation, and consequent muscle fiber hypertrophy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n DGKζ also contributes to the regulation of actin dynamics and cell motility. The PA produced by DGKζ activates p21–activated kinase 1 (PAK1), which in turn facilitates the release of RhoGDI from Rac1, thereby promoting Rac1 activation and consequent cytoskeletal remodeling necessary for cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nucleus of myoblasts, DGKζ localizes to nuclear speckles and the nuclear matrix where it interacts with phospholipase Cβ1; this localization is critical for proper myogenic differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, in cardiomyocytes, cardiac–specific overexpression of DGKζ suppresses pathological hypertrophy and fibrosis by modulating the DAG–PKC axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings illustrate that DGKζ functions as a multifaceted regulator of DAG–dependent signaling. Through its generation of PA, DGKζ influences immune cell activation and receptor recycling, modulates growth and mechanotransduction via the mTOR pathway, governs cytoskeletal dynamics and cell migration, and directs differentiation processes in muscle and heart. Its diverse roles underscore the enzyme’s importance in maintaining cellular homeostasis and highlight its potential as a therapeutic target across various disease contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Teresa Santos, Silvia Carrasco, David R Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamics of diacylglycerol kinase zeta translocation in living T-cells. Study of the structural domain requirements for translocation and activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200999200"}], "href": "https://doi.org/10.1074/jbc.M200999200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12015310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12015310"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rohan P Joshi, Amanda M Schmidt, Jayajit Das, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ζ isoform of diacylglycerol kinase plays a predominant role in regulatory T cell development and TCR-mediated ras signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2004373"}], "href": "https://doi.org/10.1126/scisignal.2004373"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24280043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24280043"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Enjun Yang, Brenal K Singh, Amanda M Schmidt Paustian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol Kinase ζ Is a Target To Enhance NK Cell Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1600581"}], "href": "https://doi.org/10.4049/jimmunol.1600581"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27342844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27342844"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Esther Rincón, Teresa Santos, Antonia Avila-Flores, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomics identification of sorting nexin 27 as a diacylglycerol kinase zeta-associated protein: new diacylglycerol kinase roles in endocytic recycling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M700047-MCP200"}], "href": "https://doi.org/10.1074/mcp.M700047-MCP200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17351151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17351151"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bai Luo, Stephen M Prescott, Matthew K Topham "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307153200"}], "href": "https://doi.org/10.1074/jbc.M307153200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12890670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12890670"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Antonia Avila-Flores, Teresa Santos, Esther Rincón, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of the mammalian target of rapamycin pathway by diacylglycerol kinase-produced phosphatidic acid."}]}, {"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.M412296200"}], "href": "https://doi.org/10.1074/jbc.M412296200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15632115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15632115"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jae-Sung You, Hannah C Lincoln, Chan-Ran Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.531392"}], "href": "https://doi.org/10.1074/jbc.M113.531392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24302719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24302719"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Karam Kim, Jinhee Yang, Xiao-Ping Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.44"}], "href": "https://doi.org/10.1038/emboj.2009.44"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19229292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19229292"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Camilla Evangelisti, Massimo Riccio, Irene Faenza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subnuclear localization and differentiation-dependent increased expression of DGK-zeta in C2C12 mouse myoblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.20744"}], "href": "https://doi.org/10.1002/jcp.20744"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16897754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16897754"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mutsuo Harada, Yasuchika Takeishi, Takanori Arimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol kinase zeta attenuates pressure overload-induced cardiac hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1253/circj.71.276"}], "href": "https://doi.org/10.1253/circj.71.276"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17251681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17251681"}]}]}]}
Synonyms	DGK-ZETA, HDGKZETA, DAGK5, DAGK6
Proteins	DGKZ_HUMAN
NCBI Gene ID	8525
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DGKZ has 7,679 functional associations with biological entities spanning 9 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, sequence feature) extracted from 133 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

DGKZ 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 DGKZ 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 DGKZ 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 DGKZ 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 DGKZ 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 DGKZ 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 DGKZ 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 DGKZ 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 DGKZ 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 DGKZ 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 DGKZ gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DGKZ 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 DGKZ gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DGKZ protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DGKZ 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 DGKZ gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DGKZ 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 DGKZ 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 DGKZ gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DGKZ protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DGKZ protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DGKZ protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DGKZ 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 DGKZ 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 DGKZ gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DGKZ gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DGKZ gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DGKZ gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with DGKZ gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DGKZ gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with DGKZ gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DGKZ 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 DGKZ 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 DGKZ 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 DGKZ gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DGKZ 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 DGKZ 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 DGKZ gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DGKZ 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 DGKZ from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DGKZ gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.