ARIH2 Gene

Name	ariadne RBR E3 ubiquitin protein ligase 2
Description	The protein encoded by this gene is an E3 ubiquitin-protein ligase that polyubiquitinates some proteins, tagging them for degradation. The encoded protein upregulates p53 in some cancer cells and may inhibit myelopoiesis. Several transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been determined yet. [provided by RefSeq, Nov 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARIH2, also known as Triad1, is an RBR‐type E3 ubiquitin ligase that plays a multifaceted role in maintaining cellular and immune homeostasis. In macrophages, ARIH2 directly interacts with the NACHT domain of NLRP3 and promotes its polyubiquitination via K48‐ and K63‐linked chains, thereby acting as a posttranslational negative regulator of NLRP3 inflammasome activation and subsequent interleukin‐1β maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In myeloid cells, ARIH2 expression is transcriptionally regulated by homeobox transcription factors such as HoxA10, and its induction contributes to the restraint of cytokine‐driven proliferation and emergency granulopoiesis; conversely, repression by HoxA9 shifts the balance towards cell expansion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, ARIH2 has been shown to participate in the regulation of innate immune responses, as its deficiency in dendritic cells leads to aberrant nuclear degradation of IκBβ and unchecked activation of NF‐κB, resulting in a hyperinflammatory state."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Genetic studies have further implicated rare coding variants in ARIH2 as risk factors for inflammatory bowel disease, highlighting its role in modulating inflammation at the organismal level."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, ARIH2 is functionally linked to larger ubiquitin ligase networks; by associating with neddylated Cullin–RING ligase complexes, it contributes to the specific ubiquitination and subsequent degradation of substrates involved in antiviral defense—for example, facilitating CRL5‐mediated turnover of APOBEC3 proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " ARIH2 also influences protein homeostasis in non‐immune tissues: it regulates the accumulation and aggregation of proteins such as PABPN1 in skeletal muscle, thereby impacting muscle integrity and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, ARIH2 has been implicated in the modulation of p53 stability and neuronal apoptosis, as well as in the regulation of ciliary signaling through control of Smoothened (Smo) ubiquitination, underscoring its diverse roles across cellular processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Akira Kawashima, Tadayoshi Karasawa, Kenji Tago, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARIH2 Ubiquitinates NLRP3 and Negatively Regulates NLRP3 Inflammasome Activation in Macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1700184"}], "href": "https://doi.org/10.4049/jimmunol.1700184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29021376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29021376"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hao Wang, Ling Bei, Chirag A Shah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HoxA10 influences protein ubiquitination by activating transcription of ARIH2, the gene encoding Triad1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.213975"}], "href": "https://doi.org/10.1074/jbc.M110.213975"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21454682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21454682"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hao Wang, Ling Bei, Chirag A Shah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HoxA10 Terminates Emergency Granulopoiesis by Increasing Expression of Triad1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1401909"}], "href": "https://doi.org/10.4049/jimmunol.1401909"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25895533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25895533"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Amy E Lin, Gregor Ebert, Yongkai Ow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARIH2 is essential for embryogenesis, and its hematopoietic deficiency causes lethal activation of the immune system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.2478"}], "href": "https://doi.org/10.1038/ni.2478"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23179078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23179078"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Natalie J Prescott, Benjamin Lehne, Kristina Stone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pooled sequencing of 531 genes in inflammatory bowel disease identifies an associated rare variant in BTNL2 and implicates other immune related genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1004955"}], "href": "https://doi.org/10.1371/journal.pgen.1004955"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25671699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25671699"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ruth Hüttenhain, Jiewei Xu, Lily A Burton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2019.05.008"}], "href": "https://doi.org/10.1016/j.chom.2019.05.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31253590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31253590"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ryan J Lumpkin, Alla S Ahmad, Rachel Blake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Mechanism of NEDD8 Activation of CUL5 Ubiquitin E3 Ligases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.RA120.002414"}], "href": "https://doi.org/10.1074/mcp.RA120.002414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33268465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33268465"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Vered Raz, Hellen Buijze, Yotam Raz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel feed-forward loop between ARIH2 E3-ligase and PABPN1 regulates aging-associated muscle degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2013.12.011"}], "href": "https://doi.org/10.1016/j.ajpath.2013.12.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24486325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24486325"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chunshuai Wu, Huiyu Zhang, Hongxiang Hong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E3 ubiquitin ligase Triad1 promotes neuronal apoptosis by regulating the p53-caspase3 pathway after spinal cord injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Somatosens Mot Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/08990220.2021.1986385"}], "href": "https://doi.org/10.1080/08990220.2021.1986385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34641746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34641746"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Bo Lv, Michael W Stuck, Paurav B Desai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.202010177"}], "href": "https://doi.org/10.1083/jcb.202010177"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34161574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34161574"}]}]}]}
Synonyms	ARI2, TRIAD1
Proteins	ARI2_HUMAN
NCBI Gene ID	10425
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARIH2 has 6,474 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 ARIH2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARIH2 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 ARIH2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ARIH2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARIH2 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 ARIH2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARIH2 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 ARIH2 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 ARIH2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing ARIH2 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 ARIH2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARIH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ARIH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ARIH2 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 ARIH2 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 ARIH2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ARIH2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ARIH2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ARIH2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ARIH2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ARIH2 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 ARIH2 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 ARIH2 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 ARIH2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARIH2 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 ARIH2 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 ARIH2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARIH2 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 ARIH2 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 ARIH2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ARIH2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.