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Literature summary for 2.7.1.30 extracted from
- Glycerol kinase interacts with nuclear receptor NR4A1 and regulates glucose metabolism in the liver (2019), FASEB J., 33, 6736-6747 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene gyk, recombinant expression of Myc-tagged enzyme Gyk in transfected C57BL/6 mice, CHO and HepG2 cells are cotransfected with pEGFP-NR4A1 and pDsRed-Gyk expression vectors, Interaction analysis of NR4A1 and Gyk isozyme b via yeast 2-hybrid system. Recombinant expression of GST-tagged Gyk in Escherichia coli | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| C256R | site-directed mutagenesis, mutation Gyk766AtoG, inactive mutant | Homo sapiens |
| M428T | site-directed mutagenesis, mutation Gyk1283TtoC, inactive mutant | Homo sapiens |
| additional information | NR4A11-250, NR4A11-375, NR4A1251-375, NR4A1251-598, and NR4A1376-598 proteins are obtained from whole-cell lysates of HEK293 cells transfected with the corresponding vectors. Selected Gyk isoform b-targeting small interfering RNA (siRNA)1555 oligonucleotides. Gyk inhibits the effects of NR4A1 on hepatic gluconeogenesis in diabetic mice | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| nucleus | - |
Homo sapiens | 5634 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens |  |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + glycerol | Homo sapiens | - |
ADP + sn-glycerol 3-phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P32189 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant GST-tagged Gyk from Escherichia coli by glutathione affinity chromatography | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| hepatocyte | - |
Homo sapiens | - |
| liver | Gyk isoform b | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + glycerol | - |
Homo sapiens | ADP + sn-glycerol 3-phosphate | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| GYK | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.2 | - |
assay at | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | glycerol kinase interacts with nuclear receptor NR4A1 and regulates glucose metabolism in the liver, Gyk interacts with NR4A1 in the nucleus | Homo sapiens |
| additional information | NR4A1-Gyk b interaction analysis using protein fragments | Homo sapiens |
| physiological function | glycerol kinase (Gyk), consisting of 4 isoforms, plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP-dependent reaction. The nuclear orphan receptor subfamily 4 group A member (NR4A)-1 (also known as Nur77, NGFI-B, NAK-1, or TR3is) an important regulator of hepatic glucose homeostasis and lipid metabolism in adipose tissue. Nuclear Gyk isoform b is a corepressor of NR4A1 in the liver. This recruitment is dependent on the C-terminal ligand-binding domain instead of the N-terminal activation function 1 domain, which interacts with other NR4A1 coregulators. NR4A1 transcriptional activity is inhibited by Gyk via protein-protein interaction but not enzymatic activity. Moreover, Gyk overexpression suppresses NR4A1 ability to regulate the expression of target genes involved in hepatic gluconeogenesis in vitro and in vivo as well as blood glucose regulation, which is observed in both unfed and diabetic transfected mice. Moonlighting function of nuclear Gyk isozyme b, which acts as a coregulator of NR4A1, participating in the regulation of hepatic glucose homeostasis in the unfed state and diabetes. The Gyk activity does not affect the interaction between Gyk and NR4A1, Gyk antagonizes the effects of NR4A1 on hepatic gluconeogenesis in vitro and in vivo | Homo sapiens |
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