TOB2 Gene

Name	transducer of ERBB2, 2
Description	TOB2 belongs to the TOB (see TOB1; MIM 605523)/BTG1 (MIM 109580) family of antiproliferative proteins, which are involved in the regulation of cell cycle progression.[supplied by OMIM, Apr 2004]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTOB2, a member of the BTG/Tob family, functions as an anti‐proliferative tumor suppressor. In cellular transformation studies, TOB2 is shown to be inhibited by oncogenic microRNAs: miR‑378 targets TOB2 to promote transforming signals via de‐repression of cyclin D1, while in hepatocellular carcinoma, miR‑362‑3p downregulates TOB2 to enhance cell proliferation. In addition, TOB2 has been implicated in regulating osteogenic differentiation, as its interaction with miR‑375 modulates both proliferation and differentiation of stem cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, TOB2 participates in controlling mRNA turnover by promoting deadenylation. It does so by simultaneously interacting with the CAF1‑CCR4 deadenylase complex and the poly(A)‑binding protein (PABP), thereby enhancing global mRNA decay and contributing to its antiproliferative roles. Its protein levels are tightly regulated by the ubiquitin–proteasome system, whereby signals in the C‑terminal region dictate its stability. Moreover, phosphorylation events, particularly those mediated by c‑Jun N‑terminal kinase (JNK), modulate TOB2 function: distinct phosphorylation sites either impair or promote its interaction with PABP, influencing mRNA deadenylation and decay of transcripts coding for cell cycle regulators."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWhile other oncogenic signals such as TNFα‑induced ErbB‑2 activation drive proliferation through alternative pathways, the studies summarized here underscore TOB2’s multifaceted role in restraining cell growth. Collectively, these findings highlight TOB2 as an important node that links microRNA‐mediated regulation, post‑transcriptional mRNA decay, and cell cycle control, ultimately contributing to its tumor suppressive function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Feng, Z Li, M Aau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myc/miR-378/TOB2/cyclin D1 functional module regulates oncogenic transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2010.602"}], "href": "https://doi.org/10.1038/onc.2010.602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21242960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21242960"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hongxing Shen, Wenjuan Li, Yuan Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of miR-362-3p Modulates Proliferation and Anchorage-Independent Growth by Directly Targeting Tob2 in Hepatocellular Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.25110"}], "href": "https://doi.org/10.1002/jcb.25110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25649327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25649327"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yan-Hua Wang, Shi-Ying Li, Shu-Jing Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-375 promotes human periodontal ligament stem cells proliferation and osteogenic differentiation by targeting transducer of ERBB2, 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Oral Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.archoralbio.2020.104818"}], "href": "https://doi.org/10.1016/j.archoralbio.2020.104818"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32619704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32619704"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hitoshi Sasajima, Koji Nakagawa, Hideyoshi Yokosawa "}, {"type": "b", "children": [{"type": "t", "text": "Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Biochem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1432-1033.2002.03052.x"}], "href": "https://doi.org/10.1046/j.1432-1033.2002.03052.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12135500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12135500"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nader Ezzeddine, Chyi-Ying A Chen, Ann-Bin Shyu "}, {"type": "b", "children": [{"type": "t", "text": "Evidence providing new insights into TOB-promoted deadenylation and supporting a link between TOB's deadenylation-enhancing and antiproliferative activities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.06370-11"}], "href": "https://doi.org/10.1128/MCB.06370-11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22252318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22252318"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chyi-Ying A Chen, Krista Strouz, Kai-Lieh Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tob2 phosphorylation regulates global mRNA turnover to reshape transcriptome and impact cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.073528.119"}], "href": "https://doi.org/10.1261/rna.073528.119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32404348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32404348"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Martín A Rivas, Mercedes Tkach, Wendy Beguelin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transactivation of ErbB-2 induced by tumor necrosis factor alpha promotes NF-kappaB activation and breast cancer cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res Treat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10549-009-0546-3"}], "href": "https://doi.org/10.1007/s10549-009-0546-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19760502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19760502"}]}]}]}
Synonyms	TOB4, TOBL, TROB2
Proteins	TOB2_HUMAN
NCBI Gene ID	10766
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TOB2 has 6,607 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 109 datasets.

Click the + buttons to view associations for TOB2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TOB2 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 TOB2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TOB2 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 TOB2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TOB2 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 TOB2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TOB2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TOB2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TOB2 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 TOB2 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 TOB2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TOB2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TOB2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 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 TOB2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TOB2 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 TOB2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TOB2 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 TOB2 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 TOB2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TOB2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing TOB2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of TOB2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of TOB2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of TOB2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TOB2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.