PTPN4 Gene

HGNC Family	Phosphatases
Name	protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte)
Description	The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPTPN4 (also known as PTP‐MEG1) is a multifaceted non‐receptor protein tyrosine phosphatase whose activity is tightly regulated by its modular structure. Structural and biophysical studies have demonstrated that its PDZ domain exerts an autoinhibitory effect on the catalytic phosphatase domain. Binding of specific PDZ ligands—notably including peptides derived from endogenous partners and viral oncoproteins such as HPV16 E6—relieves this inhibition by disrupting transient interdomain contacts. A conserved hydrophobic patch within the interdomain linker further modulates this regulatory mechanism, highlighting the importance of intramolecular communication for substrate specificity and efficient dephosphorylation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neural cells and neuroglioma models, PTPN4 plays a pro-survival role by preventing apoptosis. Notably, the recruitment of the mitogen-activated protein kinase p38γ via a tight interaction with PTPN4’s PDZ domain not only brings the kinase into close proximity but also releases the phosphatase’s autoinhibition. This ligand-induced activation enables PTPN4 to dephosphorylate p38γ, thereby modulating intracellular signaling pathways that counteract cell death processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the immune system, PTPN4 contributes to T cell receptor signalling by dephosphorylating key residues on receptor components such as the ITAMs of the TCR ζ subunit. In addition, its interaction with adaptor proteins like CrkI suggests a role in tempering cell proliferation and motility. Although studies in knockout mouse models imply that redundant phosphatases may compensate for its loss, these findings underscore PTPN4’s participation in fine-tuning T cell activation and downstream signalling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn oncogenesis, PTPN4 functions as a tumor suppressor. In colorectal cancer, loss-of-function mutations in PTPN4 lead to unchecked STAT3 activation as the phosphatase fails to dephosphorylate STAT3 at the Tyr705 residue, fostering enhanced cell growth and clonogenicity. Similarly, in prostate cancer, microRNA-375 has been shown to suppress PTPN4 expression, resulting in stabilization of phosphorylated STAT3 and promoting malignant progression. These mechanisms illustrate how disruption of PTPN4 activity can contribute to tumorigenesis and resistance to therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies further associate PTPN4 with neurodevelopmental and neurological disorders. De novo deletions of the PTPN4 locus have been identified in individuals exhibiting Rett-like phenotypes, and in uremic encephalopathy models a circRNA derived from the PTPN4 gene modulates cognitive function. Here, the circRNA sequesters miR-301a-3p, thereby enhancing FOXO3 expression and upregulating ZO-1 to restore the integrity of the blood-brain barrier. Together, these observations point to a broader impact of PTPN4 on neural development and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pierre Maisonneuve, Célia Caillet-Saguy, Bertrand Raynal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.13024"}], "href": "https://doi.org/10.1111/febs.13024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25158884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25158884"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xian Xiao, Qiang-Hua He, Li-Yan Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comput Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.compbiolchem.2016.11.005"}], "href": "https://doi.org/10.1016/j.compbiolchem.2016.11.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27923202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27923202"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Célia Caillet-Saguy, Angelo Toto, Raphael Guerois, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the Human Phosphatase PTPN4 by the inter-domain linker connecting the PDZ and the phosphatase domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-08193-6"}], "href": "https://doi.org/10.1038/s41598-017-08193-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28801650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28801650"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hye Seon Lee, Hye-Yeoung Yun, Eun-Woo Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Microbiol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12275-022-1606-1"}], "href": "https://doi.org/10.1007/s12275-022-1606-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35089587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35089587"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pierre Maisonneuve, Célia Caillet-Saguy, Marie-Christine Vaney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.707208"}], "href": "https://doi.org/10.1074/jbc.M115.707208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27246854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27246854"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jennifer A Young, Amy M Becker, Jennifer J Medeiros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of dephosphorylating the TCR ITAMs and regulating NF-kappaB, is dispensable for T cell development and/or T cell effector functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2008.05.023"}], "href": "https://doi.org/10.1016/j.molimm.2008.05.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18614237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18614237"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Juan Zhou, Bingbing Wan, Jingxuan Shan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTPN4 negatively regulates CrkI in human cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2478/s11658-013-0090-3"}], "href": "https://doi.org/10.2478/s11658-013-0090-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23666597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23666597"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bing-Dong Zhang, Yue-Rui Li, Li-Dan Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.14031"}], "href": "https://doi.org/10.1111/cas.14031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31025789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31025789"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Junqing Gan, Shan Liu, Yu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s12276-022-00837-6"}], "href": "https://doi.org/10.1038/s12276-022-00837-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36042375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36042375"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sarah L Williamson, Carolyn J Ellaway, Greg B Peters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2014.249"}], "href": "https://doi.org/10.1038/ejhg.2014.249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25424712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25424712"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yuhan Liu, Yanling Qin, Yanning Zhang "}, {"type": "b", "children": [{"type": "t", "text": "circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood-brain barrier integrity and cognitive function in uremic encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Toxicol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10565-024-09865-6"}], "href": "https://doi.org/10.1007/s10565-024-09865-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38630149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38630149"}]}]}]}
Synonyms	PTPMEG1, MEG, PTPMEG
Proteins	PTN4_HUMAN
NCBI Gene ID	5775
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PTPN4 has 5,720 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, 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 PTPN4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PTPN4 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 PTPN4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PTPN4 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 PTPN4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PTPN4 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 PTPN4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PTPN4 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PTPN4 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 PTPN4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PTPN4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PTPN4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PTPN4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PTPN4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PTPN4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PTPN4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 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 PTPN4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PTPN4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PTPN4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PTPN4 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 PTPN4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PTPN4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.