1. Gene Aliases

Acyl-CoA Thioesterase 1, CTE-1, LACH2, ACH2, Inducible Cytosolic Acyl-Coenzyme A Thioester Hydrolase, Long Chain Acyl-CoA Thioester Hydrolase, Palmitoyl-Coenzyme A Thioesterase, Acyl-Coenzyme A Thioesterase 1, Long Chain Acyl-CoA Hydrolase, EC 3.1.2.2, CTE-Ib, CTE-I, EC 3.1.2.-, CTE1.

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=Acot1#aliases_descriptions]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

acyl-CoA metabolic process [The chemical reactions and pathways involving acyl-CoA, any derivative of coenzyme A in which the sulfhydryl group is in thiolester linkage with an acyl group. GO:0006637]

fatty acid metabolic process [The chemical reactions and pathways involving fatty acids, aliphatic monocarboxylic acids liberated from naturally occurring fats and oils by hydrolysis. GO:0006631]

long-chain fatty acid metabolic process [The chemical reactions and pathways involving a long-chain fatty acid, a fatty acid with an aliphatic tail of 13 to 21 carbons. GO:0001676]

negative regulation of cardiac muscle cell apoptotic process [Any process that decreases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death. GO:0010667]

very long-chain fatty acid metabolic process [The chemical reactions and pathways involving a very long chain fatty acid, a fatty acid with an aliphatic tail of 22 or more carbons. GO:0000038]

MSigDB Signatures:

WP_CHOLESTEROL_BIOSYNTHESIS_PATHWAY_IN_HEPATOCYTES: Cholesterol biosynthesis pathway in hepatocytes [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CHOLESTEROL_BIOSYNTHESIS_PATHWAY_IN_HEPATOCYTES.html]

REACTOME_METABOLISM_OF_LIPIDS: Metabolism of lipids [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_LIPIDS.html]

REACTOME_FATTY_ACID_METABOLISM: Fatty acid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_FATTY_ACID_METABOLISM.html]

WP_7_OXO_C_AND_7_BETA_HC_PATHWAYS: 7 oxo C and 7 beta HC pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_7_OXO_C_AND_7_BETA_HC_PATHWAYS.html]

WP_OMEGA_3_OMEGA_6_FATTY_ACID_SYNTHESIS: Omega 3 omega 6 fatty acid synthesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_OMEGA_3_OMEGA_6_FATTY_ACID_SYNTHESIS.html]

REACTOME_MITOCHONDRIAL_FATTY_ACID_BETA_OXIDATION: Mitochondrial Fatty Acid Beta-Oxidation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_MITOCHONDRIAL_FATTY_ACID_BETA_OXIDATION.html]

KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS: Biosynthesis of unsaturated fatty acids [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS.html]

WP_OXYSTEROLS_DERIVED_FROM_CHOLESTEROL: Oxysterols derived from cholesterol [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_OXYSTEROLS_DERIVED_FROM_CHOLESTEROL.html]

7. Gene Descriptions

NCBI Gene Summary: Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

GeneCards Summary: ACOT1 (Acyl-CoA Thioesterase 1) is a Protein Coding gene. Diseases associated with ACOT1 include Aztreonam Allergy and Cefaclor Allergy. Among its related pathways are Fatty acid metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include hydrolase activity and palmitoyl-CoA hydrolase activity. An important paralog of this gene is ACOT2.

UniProtKB/Swiss-Prot Summary: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. More active towards saturated and unsaturated long chain fatty acyl-CoAs (C12-C20).

8. Cellular Location of Gene Product

Cytoplasmic expression in several different tissue types, including renal tubules. Localized to the mitochondria (based on antibodies targeting proteins from multiple genes). Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000184227/subcellular]

9. Mechanistic Information

Summary

Acot1 encodes for an acyl-CoA thioesterase that hydrolyzes acyl-CoAs into free fatty acids and coenzyme A, helping to regulate their respective intracellular levels [CS: 10]. This enzymatic activity is critical in the metabolism of long-chain fatty acids, impacting the cytosolic pool of acyl-CoAs and free fatty acids (FFAs) [CS: 9]. Acot1 expression is increased by PPARalpha agonists like fibrates, indicating a regulatory relationship where Acot1 facilitates the PPARalpha signaling pathway by providing FFAs as ligands [CS: 8].

In liver diseases or toxicities, compounds such as perfluorooctanoic acid (PFOA) activate PPARalpha, which then upregulates Acot1 [CS: 7]. The enhanced Acot1 expression leads to an increase in free fatty acid levels through the hydrolysis of acyl-CoAs, serving to counteract the initial toxic event by decreasing the intracellular concentration of potentially toxic long-chain acyl-CoAs [CS: 7]. Additionally, the increased availability of FFAs can be directed towards beta-oxidation for energy production when hepatocytes are under stress due to fasting or toxic insults, facilitating cellular survival by ensuring energy homeostasis [CS: 8]. By generating free fatty acids, Acot1 indirectly upregulates PPARalpha target genes, enhancing lipid catabolism and energy production [CS: 7]. Thus, the upregulation of Acot1 in response to liver toxicities aids in restoring metabolic balance by enhancing fatty acid oxidation and preventing harmful lipid accumulation [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: liver (tissue enhanced) [https://www.proteinatlas.org/ENSG00000184227/tissue]

Cell type enchanced: astrocytes, excitatory neurons, inhibitory neurons, oligodendrocyte precursor cells, oligodendrocytes, proximal tubular cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000184227/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

No biomarkers associated with disease or organ of interest were found