PJA2 Gene

HGNC Family	Zinc fingers
Name	praja ring finger 2, E3 ubiquitin protein ligase
Description	Enables protein kinase A catalytic subunit binding activity; protein kinase A regulatory subunit binding activity; and ubiquitin protein ligase activity. Involved in several processes, including proteasome-mediated ubiquitin-dependent protein catabolic process; regulation of macrophage activation; and regulation of signal transduction. Located in cytoplasm; cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPraja2 is a multifunctional RING-type E3 ubiquitin ligase that orchestrates diverse signaling pathways by targeting key regulatory proteins. In glioblastoma, praja2 ubiquitinates and degrades Mob—a core component of the Hippo cascade—thereby attenuating tumor‐suppressive signaling and promoting tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Equally, praja2 controls Ras/MAPK signaling by mediating the polyubiquitination and subsequent proteolysis of KSR1, a kinase scaffold essential for ERK activation; this regulation is evident both in studies of cancer cell growth and in maintaining the pluripotent state in embryonic stem cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn thyroid cells, praja2 fine-tunes the cAMP response by degrading the regulatory subunits of protein kinase A, thus modulating thyrocyte proliferation and hormone production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in the context of HIV infection, praja2 catalyzes a non-degradative ubiquitination of the viral Tat protein—a modification that is essential for efficient transcription elongation after Tat binds its cofactor P-TEFb—demonstrating a crucial role in viral gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPraja2 is also implicated in lung cancer biology where chimeric mRNAs comprising praja2 and FER are detected; these transcript alterations, which occur through trans-splicing rather than genomic rearrangements, correlate with increased FER expression and poorer prognostic outcomes in non-small cell lung cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its impact on oncogenic pathways, praja2 modulates immune signaling. By interacting with TYK2 and JAK1 and promoting their non-degradative ubiquitination, praja2 limits the activating phosphorylation events necessary for robust STAT signaling during type I interferon responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In clear cell renal cell carcinoma, praja2 further contributes to cellular homeostasis by forming a complex with the AP2 adaptor, thereby facilitating the ubiquitination, endocytosis, and clearance of receptor tyrosine kinases such as EGFR, ultimately restraining excessive mitogenic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Luca Lignitto, Antonietta Arcella, Maria Sepe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms2791"}], "href": "https://doi.org/10.1038/ncomms2791"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23652010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23652010"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "L Rinaldi, R Delle Donne, M Sepe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "praja2 regulates KSR1 stability and mitogenic signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2016.109"}], "href": "https://doi.org/10.1038/cddis.2016.109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27195677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27195677"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhiwei Zhao, Lin Zhu, Yanwei Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Praja2 suppresses the growth of gastric cancer by ubiquitylation of KSR1 and inhibiting MEK-ERK signal pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.202356"}], "href": "https://doi.org/10.18632/aging.202356"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33461174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33461174"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Silvia Cantara, Francesco D'Angeli, Paolo Toti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the ring ligase PRAJA2 in thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2012-2360"}], "href": "https://doi.org/10.1210/jc.2012-2360"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22948757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22948757"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tyler B Faust, Yang Li, Gwendolyn M Jang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PJA2 ubiquitinates the HIV-1 Tat protein with atypical chain linkages to activate viral transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep45394"}], "href": "https://doi.org/10.1038/srep45394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28345603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28345603"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Masanori Kawakami, Rie Ishikawa, Yosuke Amano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Detection of novel paraja ring finger 2-fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.12250"}], "href": "https://doi.org/10.1111/cas.12250"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23931849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23931849"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Samira Schiefer, Benjamin G Hale "}, {"type": "b", "children": [{"type": "t", "text": "Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-024-48800-5"}], "href": "https://doi.org/10.1038/s41467-024-48800-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38802340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38802340"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Laura Rinaldi, Francesco Chiuso, Emanuela Senatore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-024-05823-4"}], "href": "https://doi.org/10.1038/s42003-024-05823-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38379085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38379085"}]}]}]}
Synonyms	RNF131, NEURODAP1
Proteins	PJA2_HUMAN
NCBI Gene ID	9867
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PJA2 has 8,518 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 123 datasets.

Click the + buttons to view associations for PJA2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PJA2 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 PJA2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PJA2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PJA2 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 PJA2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PJA2 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 PJA2 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 PJA2 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 PJA2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PJA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PJA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PJA2 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 PJA2 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 PJA2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PJA2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PJA2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PJA2 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 PJA2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PJA2 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 PJA2 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 PJA2 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 PJA2 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 PJA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PJA2 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 PJA2 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 PJA2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PJA2 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 PJA2 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 PJA2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PJA2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.