PPP4R1 Gene

HGNC Family	Protein phosphatase 4 regulatory subunits (PPP4R)
Name	protein phosphatase 4, regulatory subunit 1
Description	This gene encodes one of several alternate regulatory subunits of serine/threonine protein phosphatase 4 (PP4). The protein features multiple HEAT repeats. This protein forms a complex with PP4RC. This complex may have a distinct role from other PP4 complexes, including regulation of HDAC3 (Zhang et al., PMID: 15805470). There is also a transcribed pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPP4R1 functions as a critical regulatory adaptor within the PP4 holoenzyme that modulates NF‑κB signaling in immune cells. In T lymphocytes, PP4R1 bridges the inhibitor of NF‑κB kinase (IKK) complex with the catalytic phosphatase PP4c to target and dephosphorylate IKK, thereby acting as an activation‐induced negative regulator that prevents prolonged NF‑κB activation and T cell hyperactivity. In addition, PP4R1 is co‑opted by oncogenic viruses such as Merkel cell polyomavirus, where the viral small T antigen hijacks PP4R1 and PP4c to engage the NEMO adaptor protein, ultimately dampening host pro‑inflammatory cytokine responses. PP4R1 also interacts with key signal transducers including TRAF2 and TRAF6—mediating dephosphorylation events and reducing polyubiquitination—to further modulate NF‑κB and AP1 signaling. Moreover, dynamic interactions with other cellular proteins, as seen in competition with AMBRA1 for binding to the PP4 complex, underscore PP4R1’s pivotal role in determining IKK phosphorylation status."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immunoregulatory functions, PP4R1 has emerged as a potent oncogene in several solid tumors. In non‑small cell lung cancer, PP4R1 is overexpressed and contributes to malignant progression by promoting cell proliferation, migration, and invasion via cooperation with factors such as high mobility group AT‑hook 2 and activation of MAPK/ERK signaling. Similarly, in gallbladder cancer PP4R1 enhances tumorigenesis by interacting with pyruvate kinase‑M2 (PKM2) to facilitate ERK1/2‑mediated nuclear translocation of PKM2, thereby reprogramming tumor glycolysis and favoring metastatic behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies reveal that PP4R1 is a multifaceted regulator whose context‑dependent actions can either restrain immune signaling or, when aberrantly expressed, drive tumor aggressiveness. Its ability to target key signaling nodes—from IKK dephosphorylation and TRAF regulation to collaboration with metabolic and EMT‑promoting pathways—positions PP4R1 as a potential biomarker and therapeutic target for inflammatory disorders and various cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "7"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Markus Brechmann, Thomas Mock, Dorothee Nickles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A PP4 holoenzyme balances physiological and oncogenic nuclear factor-kappa B signaling in T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2012.07.014"}], "href": "https://doi.org/10.1016/j.immuni.2012.07.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23084358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23084358"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hussein Abdul-Sada, Marietta Müller, Rajni Mehta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.15836"}], "href": "https://doi.org/10.18632/oncotarget.15836"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28445980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28445980"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Paul Hadweh, Hasem Habelhah, Elliott Kieff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-κB activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2014.08.001"}], "href": "https://doi.org/10.1016/j.cellsig.2014.08.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25134449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25134449"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Weimin Xu, Zhebin Hua, Yaosheng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMBRA1 promotes intestinal inflammation by antagonizing PP4R1/PP4c mediated IKK dephosphorylation in an autophagy-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-024-01275-9"}], "href": "https://doi.org/10.1038/s41418-024-01275-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38424148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38424148"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bin Wang, Lin-Yue Pan, Ning Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.23168"}], "href": "https://doi.org/10.1002/mc.23168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32077156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32077156"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xunxia Zhu, Xiaoyu Chen, Xiaoyong Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PP4R1 accelerates the malignant progression of NSCLC via up-regulating HSPA6 expression and HSPA6-mediated ER stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2023.119588"}], "href": "https://doi.org/10.1016/j.bbamcr.2023.119588"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37739270"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37739270"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhiqiang He, Yuhan Zhong, Tianrun Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PP4R1 promotes glycolysis and gallbladder cancer progression through facilitating ERK1/2 mediated PKM2 nuclear translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2024.216677"}], "href": "https://doi.org/10.1016/j.canlet.2024.216677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38301910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38301910"}]}]}]}
Synonyms	PP4R1, PP4(RMEG)
Proteins	PP4R1_HUMAN
NCBI Gene ID	9989
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPP4R1 has 6,657 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 120 datasets.

Click the + buttons to view associations for PPP4R1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP4R1 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 PPP4R1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPP4R1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPP4R1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPP4R1 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 PPP4R1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PPP4R1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PPP4R1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPP4R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPP4R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 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 PPP4R1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPP4R1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPP4R1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPP4R1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PPP4R1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PPP4R1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PPP4R1 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 PPP4R1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPP4R1 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 PPP4R1 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 PPP4R1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPP4R1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	GAD Gene-Disease Associations	diseases associated with PPP4R1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PPP4R1 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 PPP4R1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.