THEM4 Gene

Name	thioesterase superfamily member 4
Description	Protein kinase B (PKB) is a major downstream target of receptor tyrosine kinases that signal via phosphatidylinositol 3-kinase. Upon cell stimulation, PKB is translocated to the plasma membrane, where it is phosphorylated in the C-terminal regulatory domain. The protein encoded by this gene negatively regulates PKB activity by inhibiting phosphorylation. Transcription of this gene is commonly downregulated in glioblastomas. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCTMP, also known as THEM4, is a modulator of Akt/PKB signaling that has been shown to exhibit context‐dependent functions. In some studies, overexpression of CTMP was found to induce the translocation of Akt to the plasma membrane, thereby enhancing its phosphorylation at key regulatory residues and promoting the phosphorylation of downstream targets such as GSK‑3β and FoxO1, which in turn augments cellular activities including glucose transport and glycogen synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast, other investigations have reported a tumor suppressor–like activity whereby CTMP, initially identified as a PKB binding partner, inhibits Akt activation. In addition, CTMP localizes to the mitochondria where its proper maturation is essential for its pro‑apoptotic function, with mitochondrial release of CTMP correlating with enhanced caspase activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its direct modulation of Akt phosphorylation, CTMP/THEM4 plays a pivotal role in regulating mitochondrial-mediated apoptosis and cancer progression. In lung carcinoma cells, CTMP alters mitochondrial morphology and reduces the expression of OPA1, promoting cytochrome c release and subsequent apoptotic events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In head and neck squamous cell carcinoma, elevated CTMP expression correlates with increased Akt and GSK‑3β phosphorylation, driving epithelial–mesenchymal transition and enhanced tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in HER2‑enriched and triple‑negative breast cancers, high CTMP levels have been linked to trastuzumab resistance and increased metastatic potential through Akt‑dependent signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent work has further expanded the functional repertoire of THEM4 by integrating it into metabolic regulatory networks. For example, ENOPH1, an enzyme involved in L‑methionine biosynthesis, facilitates activation of the PI3K/Akt/mTOR signaling axis by regulating THEM4, thereby promoting glioma cell proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, reviews of type II acyl‑coenzyme A thioesterases highlight that CTMP (also termed THEM4) not only governs Akt signaling but also may impact lipid metabolism, brain injury responses, and mitochondrial function, underscoring its multifaceted role in cellular physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiraku Ono, Hideyuki Sakoda, Midori Fujishiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00570.2006"}], "href": "https://doi.org/10.1152/ajpcell.00570.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17615157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17615157"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Arnaud Parcellier, Lionel A Tintignac, Elena Zhuravleva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxy-Terminal Modulator Protein (CTMP) is a mitochondrial protein that sensitizes cells to apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2009.01.016"}], "href": "https://doi.org/10.1016/j.cellsig.2009.01.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19168129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19168129"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Longzhen Piao, Yuwen Li, Keum-Jin Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2121-10-53"}], "href": "https://doi.org/10.1186/1471-2121-10-53"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19604401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19604401"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Soon-Kyung Hwang, Arash Minai-Tehrani, Kyeong-Nam Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxyl-terminal modulator protein induces apoptosis by regulating mitochondrial function in lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2011.1319"}], "href": "https://doi.org/10.3892/ijo.2011.1319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22200884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22200884"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jae Won Chang, Seung-Nam Jung, Ju-Hee Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep28503"}], "href": "https://doi.org/10.1038/srep28503"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27328758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27328758"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yu-Chia Chen, Hao-Yi Li, Jui-Lin Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CTMP, a predictive biomarker for trastuzumab resistance in HER2-enriched breast cancer patient."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.10719"}], "href": "https://doi.org/10.18632/oncotarget.10719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27447863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27447863"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Cheng-Han Lin, Wen-Der Lin, Yun-Chin Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41417-022-00559-x"}], "href": "https://doi.org/10.1038/s41417-022-00559-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36400965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36400965"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bo Wang, Xin Xu, Xi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enolase-phosphatase 1 acts as an oncogenic driver in glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.29926"}], "href": "https://doi.org/10.1002/jcp.29926"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32654229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32654229"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Huonggiang Nguyen, Seon-Hwan Kim, Uijin Juang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overview of carboxyl‑terminal modulator protein 1 and its importance in various metabolic regulations (Review)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2024.13282"}], "href": "https://doi.org/10.3892/mmr.2024.13282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38994770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38994770"}]}]}]}
Synonyms	CTMP
Proteins	THEM4_HUMAN
NCBI Gene ID	117145
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

THEM4 has 5,529 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for THEM4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

THEM4 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 THEM4 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 THEM4 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 THEM4 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 THEM4 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 THEM4 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 THEM4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of THEM4 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 THEM4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of THEM4 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 THEM4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with THEM4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with THEM4 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 THEM4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of THEM4 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 THEM4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing THEM4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing THEM4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with THEM4 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 THEM4 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 THEM4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with THEM4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with THEM4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of THEM4 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 THEM4 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 THEM4 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 THEM4 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 THEM4 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 THEM4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with THEM4 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 THEM4 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 THEM4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of THEM4 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 THEM4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with THEM4 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 THEM4 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of THEM4 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 THEM4 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 THEM4 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 THEM4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
	GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations	transcription factor perturbations changing expression of THEM4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.