PTP4A2 Gene

HGNC Family	Phosphatases
Name	protein tyrosine phosphatase type IVA, member 2
Description	The protein encoded by this gene belongs to a small class of the protein tyrosine phosphatase (PTP) family. PTPs are cell signaling molecules that play regulatory roles in a variety of cellular processes. PTPs in this class contain a protein tyrosine phosphatase catalytic domain and a characteristic C-terminal prenylation motif. This PTP has been shown to primarily associate with plasmic and endosomal membrane through its C-terminal prenylation. This PTP was found to interact with the beta-subunit of Rab geranylgeranyltransferase II (beta GGT II), and thus may function as a regulator of GGT II activity. Overexpression of this gene in mammalian cells conferred a transformed phenotype, which suggested its role in tumorigenesis. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 11, 12 and 17. [provided by RefSeq, Aug 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPTP4A2, also known as PRL‐2, is a member of the phosphatases of regenerating liver that function as dual specificity phosphatases with oncogenic potential. Experimental overexpression studies have demonstrated that PTP4A2 can drive malignant transformation by accelerating the transition from G1 to S phase, in part through down‐regulation of cell cycle inhibitors such as p21. In addition, widespread expression in normal tissues suggests that while PTP4A2 may serve housekeeping functions, its deregulation can contribute to increased cell proliferation, anchorage‐independent growth, and enhanced migratory capacity in cancer cells, as evidenced by studies in breast and lung cancer models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in promoting proliferation and motility, PTP4A2 plays an important part in cellular signaling and metabolic reprogramming. PTP4A2 is intimately involved in the regulation of intracellular magnesium levels through its association with the CNNM family of magnesium transport regulators and modulation of the TRPM7 channel. Under magnesium-depleted conditions, activation of the AMPK/mTORC2 pathway leads to enhanced PTP4A2 expression, which in turn can disrupt regulatory protein–protein interactions at the membrane. Moreover, PTP4A2 has been shown to dephosphorylate PTEN at a critical tyrosine residue, thereby facilitating its ubiquitination and proteasomal degradation—a process that promotes oncogenic AKT signaling. These findings underscore the enzyme’s role as both a regulator of ion homeostasis and a modulator of key tumor suppressor pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinical analyses further support the relevance of PTP4A2 in cancer biology. In breast cancer biopsies, elevated PTP4A2 mRNA expression correlates with hormone receptor positivity and is associated with improved overall and disease-free survival, suggesting that its expression may offer prognostic value. In contrast, functional studies in hematopoietic malignancies and hepatocellular carcinoma indicate that ectopic expression of PTP4A2 enhances responses to growth factors, increases cell migration, reduces adhesion, and promotes features of malignant progression. Collectively, these data position PTP4A2 as a multifaceted contributor to cancer progression, not only by stimulating cell proliferation and migration but also by modulating metabolic and survival signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sean R Werner, Paul A Lee, Matthew W DeCamp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0304-3835(03)00517-2"}], "href": "https://doi.org/10.1016/s0304-3835(03"}, {"type": "t", "text": "00517-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14643450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14643450"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carmen M Dumaual, George E Sandusky, Pamela L Crowell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cellular localization of PRL-1 and PRL-2 gene expression in normal adult human tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Histochem Cytochem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1369/jhc.6A7019.2006"}], "href": "https://doi.org/10.1369/jhc.6A7019.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16957164"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16957164"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Serge Hardy, Nau Nau Wong, William J Muller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of the protein tyrosine phosphatase PRL-2 correlates with breast tumor formation and progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-10-2041"}], "href": "https://doi.org/10.1158/0008-5472.CAN-10-2041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20841483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20841483"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Y Wang, J S Lazo "}, {"type": "b", "children": [{"type": "t", "text": "Metastasis-associated phosphatase PRL-2 regulates tumor cell migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.281"}], "href": "https://doi.org/10.1038/onc.2011.281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21765462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21765462"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jung-Joo Hwang, Sang-Hyun Min, Ki-Hyuk Sin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered expression of phosphatase of regenerating liver gene family in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2011.1495"}], "href": "https://doi.org/10.3892/or.2011.1495"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21993571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21993571"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Serge Hardy, Elie Kostantin, Shan Jin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Magnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1815361116"}], "href": "https://doi.org/10.1073/pnas.1815361116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30718434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30718434"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qinglin Li, Yunpeng Bai, L Tiffany Lyle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of PRL2 phosphatase-mediated PTEN degradation and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2002964117"}], "href": "https://doi.org/10.1073/pnas.2002964117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32788364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32788364"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Serge Hardy, Yevgen Zolotarov, Jacob Coleman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2221083120"}], "href": "https://doi.org/10.1073/pnas.2221083120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36972446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36972446"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Faji Cai, Yichen Huang, Mengqi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A FRET-based screening method to detect potential inhibitors of the binding of CNNM3 to PRL2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-69818-x"}], "href": "https://doi.org/10.1038/s41598-020-69818-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32733084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32733084"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sarah A Andres, James L Wittliff, Alan Cheng "}, {"type": "b", "children": [{"type": "t", "text": "Protein tyrosine phosphatase 4A2 expression predicts overall and disease-free survival of human breast cancer and is associated with estrogen and progestin receptor status."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Horm Cancer (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12672-013-0141-2"}], "href": "https://doi.org/10.1007/s12672-013-0141-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23568563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23568563"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shoko Akiyama, Deepika Dhavan, Taolin Yi "}, {"type": "b", "children": [{"type": "t", "text": "PRL-2 increases Epo and IL-3 responses in hematopoietic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cells Mol Dis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcmd.2010.02.013"}], "href": "https://doi.org/10.1016/j.bcmd.2010.02.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20226699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20226699"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Hai-yan Ye, Ai-lin Guo, Meng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Construction of an eukaryotic expression vector for PRL-2 and its effect on human hepatocellular carcinoma cell invasiveness and migration in vitro]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nan Fang Yi Ke Da Xue Xue Bao (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17666324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17666324"}]}]}]}
Synonyms	HU-PP-1, PRL-2, PTP4A, PTP-IV1B, HH7-2, PRL2, PTP-IV1A, PTPCAAX2, OV-1
Proteins	TP4A2_HUMAN
NCBI Gene ID	8073
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PTP4A2 has 9,846 functional associations with biological entities spanning 8 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) extracted from 119 datasets.

Click the + buttons to view associations for PTP4A2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 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 PTP4A2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PTP4A2 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 PTP4A2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PTP4A2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PTP4A2 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 PTP4A2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PTP4A2 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 PTP4A2 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 PTP4A2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PTP4A2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PTP4A2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PTP4A2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PTP4A2 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 PTP4A2 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 PTP4A2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PTP4A2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PTP4A2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PTP4A2 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 PTP4A2 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 PTP4A2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PTP4A2 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 PTP4A2 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 PTP4A2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PTP4A2 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 PTP4A2 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 PTP4A2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PTP4A2 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 PTP4A2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PTP4A2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PTP4A2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.