1. Gene Aliases

Crat, CAT1, Carnitine Acetyltransferase, Carnitine Acetylase, EC 2.3.1.7, CAT, EC 2.3.1.137, EC 2.3.1, NBIA8, CrAT

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=CRAT&keywords=crat].

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

5. Links to Gene Databases

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

Pathways:

GO terms:

carnitine metabolic process, CoA-linked [The chemical reactions and pathways involving carnitine, where metabolism is linked to CoA. GO:0019254]

fatty acid beta-oxidation using acyl-CoA oxidase [A fatty acid beta-oxidation pathway in which the initial step, which converts an acyl-CoA to a trans-2-enoyl-CoA, is catalyzed by acyl-CoA oxidase; the electrons removed by oxidation pass directly to oxygen and produce hydrogen peroxide, which is cleaved by peroxisomal catalases. Fatty acid beta-oxidation begins with the addition of coenzyme A to a fatty acid, and ends when only two or three carbons remain (as acetyl-CoA or propionyl-CoA respectively). GO:0033540]

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]

medium-chain fatty acid metabolic process [The chemical reactions and pathways involving a medium-chain fatty acid, a fatty acid with an aliphatic tail of 6 to 12 carbons. GO:0051791]

short-chain fatty acid metabolic process [The chemical reactions and pathways involving a fatty acid with an aliphatic tail of less than 6 carbons. GO:0046459]

MSigDB Signatures:

REACTOME_PEROXISOMAL_LIPID_METABOLISM: Peroxisomal lipid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PEROXISOMAL_LIPID_METABOLISM.html]

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

KEGG_PEROXISOME: Peroxisome [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PEROXISOME.html]

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

REACTOME_PROTEIN_LOCALIZATION: Protein localization [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PROTEIN_LOCALIZATION.html]

CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN: Genes down-regulated in hepatoblastoma (HB) tumors as compared with non-tumor (NT) adjacent tissue. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN.html]

REACTOME_PEROXISOMAL_PROTEIN_IMPORT: Peroxisomal protein import [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PEROXISOMAL_PROTEIN_IMPORT.html]

WP_FATTY_ACID_BETA_OXIDATION: Fatty acid beta oxidation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FATTY_ACID_BETA_OXIDATION.html]

REACTOME_BETA_OXIDATION_OF_PRISTANOYL_COA: Beta-oxidation of pristanoyl-CoA [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_BETA_OXIDATION_OF_PRISTANOYL_COA.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes carnitine O-acetyltransferase, a member of the carnitine acyltransferase family and a key metabolic pathway enzyme which plays an important role in energy homeostasis and fat metabolism. This enzyme catalyzes the reversible transfer of acyl groups from an acyl-CoA thioester to carnitine and regulates the ratio of acyl-CoA/CoA. It is found in both the mitochondria and the peroxisome. Alternative splicing results in transcript variants encoding different isoforms that may localize to different subcellular compartments. [provided by RefSeq, Oct 2016]

GeneCards Summary: CRAT (Carnitine O-Acetyltransferase) is a Protein Coding gene. Diseases associated with CRAT include Neurodegeneration With Brain Iron Accumulation 8 and Neurodegeneration With Brain Iron Accumulation. Among its related pathways are Peroxisomal lipid metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and carnitine O-acetyltransferase activity. An important paralog of this gene is CHAT.

UniProtKB/Swiss-Prot Summary: Catalyzes the reversible transfer of acyl groups from carnitine to coenzyme A (CoA) and regulates the acyl-CoA/CoA ratio. Also plays a crucial role in the transport of fatty acids for beta-oxidation [PMID: 15099582, PMID: 29395073]. Responsible for the synthesis of short- and branched-chain acylcarnitines [PMID: 23485643]. Active towards some branched-chain amino acid oxidation pathway (BCAAO) intermediates [PMID: 23485643]. Trans-2-enoyl-CoAs and 2-methylacyl-CoAs are poor substrates [PMID: 23485643].

8. Cellular Location of Gene Product

Cytoplasmic expression in most cell types, highly abundant in cells in seminiferous tubules. Mainly localized to the cytosol & the Golgi apparatus. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000095321/subcellular]

9. Mechanistic Information

Summary

The Crat gene's dysregulation in liver diseases and toxicities is closely tied to its function in maintaining metabolic homeostasis, especially under stress [CS: 9]. Crat, encoding carnitine O-acetyltransferase, plays a critical role in the reversible transfer of acyl groups from carnitine to coenzyme A (CoA), regulating the acyl-CoA/CoA ratio [CS: 10]. This regulation is vital in managing energy production and lipid metabolism [CS: 9]. In toxic scenarios, such as with aluminum chloride (AlCl3) exposure leading to oxidative stress and apoptosis in the liver, the upregulation of Crat suggests a protective response [CS: 7]. By transferring acyl groups to CoA, Crat facilitates the transport and beta-oxidation of fatty acids, thereby maintaining mitochondrial function and energy balance during cellular stress [CS: 9].

Moreover, in conditions like fenofibrate-induced hepatocellular preneoplastic foci, characterized by increased reactive oxygen species and oxidative stress, Crat's upregulation aids in managing the elevated demand for efficient fatty acid transport and metabolism [CS: 7]. This is crucial since beta-oxidation of fatty acids is a significant energy source during periods of liver cell regeneration and repair [CS: 8]. The efficient functioning of Crat in these scenarios helps in sustaining energy production, mitigating the accumulation of harmful fatty acids and their metabolites, and supporting liver tissue in coping with and recovering from toxic insults [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: skeletal muscle, tongue (tissue enhanced) [https://www.proteinatlas.org/ENSG00000095321/tissue]

Cell type enchanced: early spermatids, late spermatids, proximal enterocytes (cell type enhanced) [https://www.proteinatlas.org/ENSG00000095321/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

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: