PPP2R3A Gene

HGNC Family	Protein phosphatase 2 regulatory subunits (PPP2R), EF-hand domain containing
Name	protein phosphatase 2, regulatory subunit B'', alpha
Description	This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP2R3A, also known as PR72/PR130, is a regulatory subunit of the major serine/threonine phosphatase PP2A that confers substrate specificity and enables Ca²⁺‐dependent regulation of enzyme activity. The subunit contains two EF‐hand calcium-binding motifs—one of which is indispensable for coupling Ca²⁺ signals to PP2A activity—thus modulating conformational changes, subunit assembly, and proper nuclear targeting. In dopaminoceptive neurons, for example, the Ca²⁺‐sensitive PR72–PP2A complex facilitates the dephosphorylation of DARPP‑32 at Thr‑75, a key step in integrating dopaminergic and glutamatergic signaling and fine-tuning downstream neuronal responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond neuronal signaling, PPP2R3A plays a role as a negative regulator of the classical Wnt signaling cascade. Through physical and functional interaction with the Wnt antagonist Naked cuticle, the PR72 isoform limits Wnt pathway activity, thereby contributing to the modulation of embryonic development and the regulation of planar cell polarity during gastrulation movements."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPPP2R3A‐containing PP2A complexes are also integral to cell cycle control. Specific isoforms—such as PR70—target PP2A to substrates like Cdc6, enhancing its dephosphorylation and promoting its timely degradation to regulate the G₁/S transition. In addition, by facilitating dephosphorylation of key checkpoint proteins including ATM and CHK1, PPP2R3A helps maintain replication stress responses and proper cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe subunit’s role extends to the regulation of cell adhesion and migration. By binding to partners such as the LIM protein lipoma-preferred partner (LPP) via a conserved Zn²⁺ finger–like motif, PPP2R3A directs PP2A activity at sites of dynamic adhesion. This interaction modulates focal contact maturation and impacts cell motility, highlighting its importance in tissue organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also supports a tumor suppressor role for PPP2R3A. In colon cancer, promoter hypermethylation is closely associated with a significant decrease in mRNA expression, suggesting that loss of PPP2R3A function may contribute to oncogenic transformation. Furthermore, recent studies indicate that PPP2R3A can influence cancer metabolism through its regulatory interplay with hexokinase 1 in hepatocellular carcinoma, and its overall impact on oncogenic signaling is underscored by its wide-ranging involvement in maintaining cell identity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, while strategies such as the development of DEPhosphorylation TArgeting Chimeras (DEPTAC) have been employed to selectively enhance tau dephosphorylation by PP2A complexes containing alternative B subunits, these studies highlight the broader therapeutic potential of modulating PP2A holoenzyme composition. This concept reinforces the significance of regulatory subunits like PPP2R3A in orchestrating precise dephosphorylation events across diverse cellular contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Veerle Janssens, Jan Jordens, Ilse Stevens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and functional analysis of two Ca2+-binding EF-hand motifs in the B\"/PR72 subunit of protein phosphatase 2A."}]}, {"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.M211717200"}], "href": "https://doi.org/10.1074/jbc.M211717200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12524438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12524438"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jung-Hyuck Ahn, Jee Young Sung, Thomas McAvoy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The B''/PR72 subunit mediates Ca2+-dependent dephosphorylation of DARPP-32 by protein phosphatase 2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0703589104"}], "href": "https://doi.org/10.1073/pnas.0703589104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17535922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17535922"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Menno P Creyghton, Giulietta Roël, Pieter J A Eichhorn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PR72, a novel regulator of Wnt signaling required for Naked cuticle function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.328905"}], "href": "https://doi.org/10.1101/gad.328905"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15687260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15687260"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anthony J Davis, Zhen Yan, Bobbie Martinez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase 2A is targeted to cell division control protein 6 by a calcium-binding regulatory subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M710313200"}], "href": "https://doi.org/10.1074/jbc.M710313200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18397887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18397887"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anja Göder, Claudia Emmerich, Teodora Nikolova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03096-0"}], "href": "https://doi.org/10.1038/s41467-018-03096-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29472538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29472538"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Veerle Janssens, Karen Zwaenepoel, Carine Rossé, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PP2A binds to the LIM domains of lipoma-preferred partner through its PR130/B″ subunit to regulate cell adhesion and migration."}]}, {"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.175778"}], "href": "https://doi.org/10.1242/jcs.175778"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26945059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26945059"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A A Dmitriev, A D Beniaminov, N V Melnikova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol (Mosk) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/S002689842001005X"}], "href": "https://doi.org/10.1134/S002689842001005X"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32392189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32392189"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Melanie Dzulko, Miriam Pons, Andreas Henke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PP2A subunit PR130 is a key regulator of cell development and oncogenic transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Rev Cancer (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbcan.2020.188453"}], "href": "https://doi.org/10.1016/j.bbcan.2020.188453"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33068647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33068647"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ning Jiao, Wan Sheng Ji, Biao Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Protein Phosphatase 2 Regulatory Subunit B\"Alpha Promotes Glycolysis by Regulating Hexokinase 1 in Hepatocellular Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Environ Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3967/bes2022.082"}], "href": "https://doi.org/10.3967/bes2022.082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35945177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35945177"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jie Zheng, Na Tian, Fei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel dephosphorylation targeting chimera selectively promoting tau removal in tauopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Signal Transduct Target Ther (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41392-021-00669-2"}], "href": "https://doi.org/10.1038/s41392-021-00669-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34262014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34262014"}]}]}]}
Synonyms	PR72, PPP2R3, PR130
Proteins	P2R3A_HUMAN
NCBI Gene ID	5523
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPP2R3A has 5,367 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 121 datasets.

Click the + buttons to view associations for PPP2R3A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPP2R3A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPP2R3A 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 PPP2R3A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPP2R3A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPP2R3A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PPP2R3A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP2R3A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPP2R3A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPP2R3A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPP2R3A gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PPP2R3A gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A 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 PPP2R3A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPP2R3A 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 PPP2R3A 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 PPP2R3A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.