Cloned (Comment) | Organism |
---|---|
ectopic expression of wild-type and mutant human DHCR24s in CHO-7 cells that are deficient for DHCR24 through specific siRNA knockout, quantitative real-time RT-PCR enzyme expression analysis | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
T110A | site-directed mutagenesis, mutation and inactivation of the phosphorylation site results in 60% loss of activity compared to wild-type | Homo sapiens |
T110E | site-directed mutagenesis, DHCR24 activity of the phosphomimetic T110E mutant is similar to wild-type activity | Homo sapiens |
Y299F | site-directed mutagenesis, compared with wild-type DHCR24, the mutant Y299F stable cells contain reduced DHCR24 mRNA expression while having comparable DHCR24 protein levels, the mutant enzyme activity is reduced by 40% compared to the wild-type | Homo sapiens |
Y300F | site-directed mutagenesis, compared with wild-type DHCR24, the mutant Y299F stable cells contain comparable DHCR24 mRNA expression while having reduced DHCR24 protein levels, the mutant enzyme activity is similar to the wild-type | Homo sapiens |
Y321F | site-directed mutagenesis, the mutant enzyme activity is similar to the wild-type | Homo sapiens |
Y507F | site-directed mutagenesis, the mutant enzyme activity is reduced by 60% compared to the wild-type | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | inhibitors of protein kinase C ablate DHCR24 activity, although not through a known phosphorylation site T110. PKC inhibitors, BIM and Ro-318220, reduce cholesterol levels and accumulate desmosterol within 4 h, indicating decreased DHCR24 activity | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
cholesta-5,24-dien-3beta-ol + NADPH + H+ | Homo sapiens | reduction of desmosterol to cholesterol is dependent on FAD | cholest-5-en-3beta-ol + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q15392 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | protein kinase C (PKC) activates DHCR24 activity through reversible phosphorylation. PKC inhibitors, BIM and Ro-318220, reduce cholesterol levels and accumulate desmosterol within 4 h, indicating decreased DHCR24 activity. Phosphorylation at T110 modulates DHCR24 activity | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HeLa cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
cholesta-5,24-dien-3beta-ol + NADPH + H+ | reduction of desmosterol to cholesterol is dependent on FAD | Homo sapiens | cholest-5-en-3beta-ol + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
3beta-hydroxysterol DELTA24-reductase | - |
Homo sapiens |
DHCR24 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | DHCR24 contains a highly conserved FAD binding domain comprising amino acids 111-203 | Homo sapiens | |
NADPH | DHCR24 activity is strictly dependent on NADPH | Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | DHCR24 is transcriptionally regulated by sterols via the sterol-regulatory element-binding protein-2 transcription factor | additional information |
General Information | Comment | Organism |
---|---|---|
malfunction | mutating residues T110, Y299, and Y507 of known phosphorylation sites inhibits DHCR24 activity. Seven missense mutations in DHCR24 have been described in desmosterolosis: R94H, R103C, E191K, N294T, K306N, Y471S, E480K. PKC inhibition results in desmosterol accumulation | Homo sapiens |
metabolism | DHCR24 is the final enzyme in cholesterol synthesis, role of signaling in regulating cholesterol homeostasis | Homo sapiens |
physiological function | the enzyme activity is regulated by signaling through kinases and reversible phosphorylation | Homo sapiens |