hydroxymethylglutaryl-CoA synthase 2 | Lanosterol biosynthesis pathway | IUPHAR/BPS Guide to PHARMACOLOGY

hydroxymethylglutaryl-CoA synthase 2

Target id: 2432

Nomenclature: hydroxymethylglutaryl-CoA synthase 2

Family: Lanosterol biosynthesis pathway

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for hydroxymethylglutaryl-CoA synthase 2 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 508 1p13-p12 HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 2
Mouse - 508 3 42.74cM Hmgcs2 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2
Rat - 508 2q34 Hmgcs2 3-hydroxy-3-methylglutaryl-CoA synthase 2
Previous and Unofficial Names
mitochondrial HMGCoA synthase | 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (HMGCS2)
PDB Id:  2WYA
Resolution:  1.7Å
Species:  Human
References:  6
Enzyme Reaction
EC Number: 2.3.3.10 Acetyl CoA + H2O + acetoacetyl CoA -> (S)-3-hydroxy-3-methylglutaryl-CoA + coenzyme A
Tissue Distribution
Liver, colon (high), testis, kidney, heart, skeletal muscles (low), pancreas (very low expression detected)
Species:  Human
Technique:  RNA blot analysis
References:  4
Liver (high expression), kidney, pancreas, testis (medium), heart and skeletal muscle (low expression)
Species:  Human
Technique:  Quantitative PCR
References:  5
Colonic epithelium
Species:  Human
Technique:  Northern blot
References:  3
Clinically-Relevant Mutations and Pathophysiology
Disease:  3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency
OMIM: 605911
Orphanet: ORPHA35701
References:  7
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human F174L 520T>C 1
Gene Expression and Pathophysiology
HMGCS2 is downregulated in colon cancer
Tissue or cell type:  Colonic epithelium
Pathophysiology:  Colon cancer
Species:  Human
Technique:  Northern blot
References:  3
General Comments
HMGCoA synthase is found in cytosolic (HMGCoA synthase 1) and mitochondrial (HMGCoA synthase 2) versions; the former associated with synthesis and the latter with ketogenesis.

References

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1. Bouchard L, Robert MF, Vinarov D, Stanley CA, Thompson GN, Morris A, Leonard JV, Quant P, Hsu BY, Boneh A et al.. (2001) Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients. Pediatr. Res., 49 (3): 326-31. [PMID:11228257]

2. Boukaftane Y, Mitchell GA. (1997) Cloning and characterization of the human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase gene. Gene, 195 (2): 121-6. [PMID:9305755]

3. Camarero N, Mascaró C, Mayordomo C, Vilardell F, Haro D, Marrero PF. (2006) Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer. Mol. Cancer Res., 4 (9): 645-53. [PMID:16940161]

4. Mascaró C, Buesa C, Ortiz JA, Haro D, Hegardt FG. (1995) Molecular cloning and tissue expression of human mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. Arch. Biochem. Biophys., 317 (2): 385-90. [PMID:7893153]

5. Puisac B, Ramos M, Arnedo M, Menao S, Gil-Rodríguez MC, Teresa-Rodrigo ME, Pié A, de Karam JC, Wesselink JJ, Giménez I et al.. (2012) Characterization of splice variants of the genes encoding human mitochondrial HMG-CoA lyase and HMG-CoA synthase, the main enzymes of the ketogenesis pathway. Mol. Biol. Rep., 39 (4): 4777-85. [PMID:21952825]

6. Shafqat N, Turnbull A, Zschocke J, Oppermann U, Yue WW. (2010) Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. J. Mol. Biol., 398 (4): 497-506. [PMID:20346956]

7. Thompson GN, Hsu BY, Pitt JJ, Treacy E, Stanley CA. (1997) Fasting hypoketotic coma in a child with deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. N. Engl. J. Med., 337 (17): 1203-7. [PMID:9337379]

Contributors

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How to cite this page

Helen E. Benson.
Lanosterol biosynthesis pathway: hydroxymethylglutaryl-CoA synthase 2. Last modified on 15/05/2015. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2432.