Literature summary for 1.3.1.72 extracted from

Luu, W.; Zerenturk, E.J.; Kristiana, I.; Bucknall, M.P.; Sharpe, L.J.; Brown, A.J.
Signaling regulates activity of DHCR24, the final enzyme in cholesterol synthesis (2014), J. Lipid Res., 55, 410-420 .

Search for more literature for 1.3.1.72

Cloned(Commentary)

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

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

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/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	Q15392	-	-

Posttranslational Modification

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

Source Tissue	Comment	Organism	Textmining
HeLa cell	-	Homo sapiens	-

Substrates and Products (Substrate)

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

Synonyms	Comment	Organism
3beta-hydroxysterol DELTA24-reductase	-	Homo sapiens
DHCR24	-	Homo sapiens

Cofactor

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

Expression

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

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

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Release 2023.1 (January 2023)