PPP2R5A Gene

HGNC Family	Protein phosphatase 2 regulatory subunits (PPP2R)
Name	protein phosphatase 2, regulatory subunit B', alpha
Description	The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an alpha isoform of the regulatory subunit B56 subfamily. Alternative transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP2R5A, the B56α regulatory subunit of protein phosphatase 2A (PP2A), is emerging as a critical specificity‐determining factor that orchestrates diverse dephosphorylation events essential for proper cell cycle and mitotic regulation. Structural and biochemical studies have revealed that PPP2R5A, as part of the PP2A–B56 family, is required for stabilizing kinetochore–microtubule attachments and tuning the phosphorylation status of key mitotic regulators—including Aurora B, Plk1, and checkpoint effectors—thereby ensuring error‐free chromosome segregation and timely mitotic exit. Detailed analyses have elucidated specific short linear motifs governing PPP2R5A interactions, as well as its role in the assembly of holoenzymes that function at the kinetochore and other subcellular sites."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPPP2R5A function and localization are subject to multiple layers of regulation. Its activity is modulated by post‐translational phosphorylation events—for example, by kinases such as PKR and PKCα—which can influence its subcellular distribution (including mitochondrial localization) and thus the dephosphorylation of substrates like cyclin G1 and CaMKIV. In addition, PPP2R5A is a direct target of microRNA‐218 in certain cancer cells, an interaction that alters downstream Wnt signaling and affects chemotherapy response. Notably, pathogenic factors such as HIV‑1 Vif also target PPP2R5A (and related B56 subunits) for degradation to elicit G2 arrest, underscoring its tumor‐suppressive and cell cycle–regulatory roles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond mitosis and cell cycle control, PPP2R5A participates in broader cellular signaling by regulating the stability and function of other key proteins, such as cyclin G1 and CaMKIV. These interactions influence not only phosphoprotein turnover but also the integration of stress responses and transcriptional programs critical for maintaining cellular homeostasis. Together, these studies underscore the central role of PPP2R5A as a versatile mediator of PP2A function, whose deregulation has important implications in cancer and other diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emily A Foley, Maria Maldonado, Tarun M Kapoor "}, {"type": "b", "children": [{"type": "t", "text": "Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2327"}], "href": "https://doi.org/10.1038/ncb2327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21874008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21874008"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daniel Leonard, Wei Huang, Sudeh Izadmehr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective PP2A Enhancement through Biased Heterotrimer Stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2020.03.038"}], "href": "https://doi.org/10.1016/j.cell.2020.03.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32315618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32315618"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sun Joo Lee, Veronica Rodriguez-Bravo, Hyunjung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PP2A"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "B56"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " phosphatase promotes the association of Cdc20 with APC/C in mitosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.201608"}], "href": "https://doi.org/10.1242/jcs.201608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28404789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28404789"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alyson K Freeman, Virna Dapic, Alvaro N A Monteiro "}, {"type": "b", "children": [{"type": "t", "text": "Negative regulation of CHK2 activity by protein phosphatase 2A is modulated by DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.9.4.10613"}], "href": "https://doi.org/10.4161/cc.9.4.10613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20160490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20160490"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jiao Wang, Zhizhi Wang, Tingting Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13238-016-0283-4"}], "href": "https://doi.org/10.1007/s13238-016-0283-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27350047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27350047"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Richard J Smith, Marilia H Cordeiro, Norman E Davey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PP1 and PP2A Use Opposite Phospho-dependencies to Control Distinct Processes at the Kinetochore."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.07.067"}], "href": "https://doi.org/10.1016/j.celrep.2019.07.067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31433993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31433993"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Vivian R Ruvolo, Svitlana M Kurinna, Kul B Karanjeet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKR regulates B56(alpha)-mediated BCL2 phosphatase activity in acute lymphoblastic leukemia-derived REH cells."}]}, {"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.M800951200"}], "href": "https://doi.org/10.1074/jbc.M800951200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18957415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18957415"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Uwe Kirchhefer, Alexander Heinick, Simone König, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase 2A is regulated by protein kinase Cα (PKCα)-dependent phosphorylation of its targeting subunit B56α at Ser41."}]}, {"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.M113.507996"}], "href": "https://doi.org/10.1074/jbc.M113.507996"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24225947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24225947"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zehang Zhuang, Fengchun Hu, Jing Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2017.5899"}], "href": "https://doi.org/10.3892/or.2017.5899"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28849187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28849187"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Daniel J Salamango, Terumasa Ikeda, Seyed Arad Moghadasi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIV-1 Vif Triggers Cell Cycle Arrest by Degrading Cellular PPP2R5 Phospho-regulators."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.09.057"}], "href": "https://doi.org/10.1016/j.celrep.2019.09.057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31665623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31665623"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Daniel J Salamango, Jennifer L McCann, Özlem Demir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional and Structural Insights into a Vif/PPP2R5 Complex Elucidated Using Patient HIV-1 Isolates and Computational Modeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00631-20"}], "href": "https://doi.org/10.1128/JVI.00631-20"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32847850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32847850"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kelie M Reece, Matthew D Mazalouskas, Brian E Wadzinski "}, {"type": "b", "children": [{"type": "t", "text": "The Balpha and Bdelta regulatory subunits of PP2A are necessary for assembly of the CaMKIV.PP2A signaling complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.06.062"}], "href": "https://doi.org/10.1016/j.bbrc.2009.06.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19538941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19538941"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Cameron P Flegg, Manisha Sharma, Cahora Medina-Palazon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear export and centrosome targeting of the protein phosphatase 2A subunit B56alpha: role of B56alpha in nuclear export of the catalytic subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.093294"}], "href": "https://doi.org/10.1074/jbc.M109.093294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20378546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20378546"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hongyun Li, Koji Okamoto, Melissa J Peart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysine-independent turnover of cyclin G1 can be stabilized by B'alpha subunits of protein phosphatase 2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00907-08"}], "href": "https://doi.org/10.1128/MCB.00907-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18981217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18981217"}]}]}]}
Synonyms	B56alpha, PR61A, B56A
Proteins	2A5A_HUMAN
NCBI Gene ID	5525
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPP2R5A has 6,925 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 128 datasets.

Click the + buttons to view associations for PPP2R5A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A 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 PPP2R5A gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP2R5A 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 PPP2R5A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPP2R5A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPP2R5A 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 PPP2R5A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPP2R5A 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 PPP2R5A 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 PPP2R5A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPP2R5A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPP2R5A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PPP2R5A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PPP2R5A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP2R5A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPP2R5A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPP2R5A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPP2R5A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PPP2R5A 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 PPP2R5A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate PPP2R5A protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PPP2R5A 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 PPP2R5A 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 PPP2R5A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPP2R5A 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 PPP2R5A 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 PPP2R5A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPP2R5A 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 PPP2R5A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PPP2R5A gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PPP2R5A gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PPP2R5A from the GeneSigDB Published Gene Signatures dataset.