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Identification
HMDB Protein ID HMDBP00040
Secondary Accession Numbers
  • 5269
Name Hydroxymethylglutaryl-CoA synthase, mitochondrial
Synonyms
  1. 3-hydroxy-3-methylglutaryl coenzyme A synthase
  2. HMG-CoA synthase
Gene Name HMGCS2
Protein Type Enzyme
Biological Properties
General Function Involved in hydroxymethylglutaryl-CoA synthase activity
Specific Function This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.
Pathways
  • (R)-mevalonate biosynthesis
  • 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
  • 3-hydroxyisobutyric acid dehydrogenase deficiency
  • 3-hydroxyisobutyric aciduria
  • 3-Methylcrotonyl Coa Carboxylase Deficiency Type I
  • 3-Methylglutaconic Aciduria Type I
  • 3-Methylglutaconic Aciduria Type III
  • 3-Methylglutaconic Aciduria Type IV
  • Beta-Ketothiolase Deficiency
  • Butanoate metabolism
  • Butyrate Metabolism
  • Isobutyryl-coa dehydrogenase deficiency
  • Isovaleric acidemia
  • Isovaleric Aciduria
  • Ketone Body Metabolism
  • Maple Syrup Urine Disease
  • Methylmalonate Semialdehyde Dehydrogenase Deficiency
  • Methylmalonic Aciduria
  • PPAR signaling pathway
  • Propionic Acidemia
  • Succinyl CoA: 3-ketoacid CoA transferase deficiency
  • Synthesis and degradation of ketone bodies
  • Terpenoid backbone biosynthesis
  • Valine, Leucine and Isoleucine Degradation
  • Valine, leucine and isoleucine degradation
Reactions
Acetyl-CoA + Water + Acetoacetyl-CoA → 3-Hydroxy-3-methylglutaryl-CoA + Coenzyme A details
3-Hydroxy-3-methylglutaryl-CoA + Coenzyme A → Acetyl-CoA + Water + Acetoacetyl-CoA details
GO Classification
Biological Process
isoprenoid biosynthetic process
response to glucagon stimulus
cholesterol biosynthetic process
cellular response to amino acid stimulus
ketone body biosynthetic process
adipose tissue development
response to testosterone stimulus
response to growth hormone stimulus
liver development
response to drug
response to ethanol
response to metal ion
response to nutrient
response to starvation
cellular response to lipopolysaccharide
cellular response to insulin stimulus
brain development
kidney development
cellular response to fatty acid
lung development
cellular response to glucocorticoid stimulus
midgut development
multicellular organismal response to stress
response to linoleic acid
response to monosaccharide stimulus
response to prostaglandin F stimulus
response to temperature stimulus
response to triglyceride
cellular lipid metabolic process
response to cAMP
Cellular Component
mitochondrial matrix
mitochondrial inner membrane
Function
catalytic activity
transferase activity
transferase activity, transferring acyl groups
transferase activity, transferring acyl groups, acyl groups converted into alkyl on transfer
hydroxymethylglutaryl-coa synthase activity
Molecular Function
hydroxymethylglutaryl-CoA synthase activity
Process
metabolic process
primary metabolic process
lipid metabolic process
cellular lipid metabolic process
isoprenoid metabolic process
isoprenoid biosynthetic process
Cellular Location
  1. Mitochondrion
Gene Properties
Chromosome Location 1
Locus 1p13-p12
SNPs HMGCS2
Gene Sequence
>1527 bp
ATGCAGCGTCTGTTGACTCCAGTGAAGCGCATTCTGCAACTGACAAGAGCGGTGCAGGAA
ACCTCCCTCACACCTGCTCGCCTGCTCCCAGTAGCCCACCAAAGGTTTTCTACAGCCTCT
GCTGTCCCCCTGGCCAAAACAGATACTTGGCCAAAGGACGTGGGCATCCTGGCCCTGGAG
GTCTACTTCCCAGCCCAATATGTGGACCAAACTGACCTGGAGAAGTATAACAATGTGGAA
GCAGGAAAGTATACAGTGGGCTTGGGCCAGACCCGTATGGGCTTCTGCTCAGTCCAAGAG
GACATCAACTCCCTGTGCCTGACGGTGGTGCAACGGCTGATGGAGCGCATACAGCTCCCA
TGGGACTCTGTGGGCAGGCTGGAAGTAGGCACTGAGACCATCATTGACAAGTCCAAAGCT
GTCAAAACAGTGCTCATGGAACTCTTCCAGGATTCAGGCAATACTGATATTGAGGGCATA
GATACCACCAATGCCTGCTACGGTGGTACTGCCTCCCTCTTCAATGCTGCCAACTGGATG
GAGTCCAGTTCCTGGGATGGTCGTTATGCCATGGTGGTCTGTGGAGACATTGCCGTCTAT
CCCAGTGGTAATGCTCGTCCCACAGGTGGGGCCGGAGCTGTGGCTATGCTGATTGGGCCC
AAGGCCCCTCTGGCCCTGGAGCGAGGGCTGAGGGGAACCCATATGGAGAATGTGTATGAC
TTCTACAAACCAAATTTGGCCTCGGAGTACCCAATAGTGGATGGGAAGCTTTCCATCCAG
TGCTACTTGCGGGCCTTGGATCGATGTTACACATCATACCGTAAAAAAATCCAGAATCAG
TGGAAGCAAGCTGGCAGCGATCGACCCTTCACCCTTGACGATTTACAGTACATGATCTTT
CATACACCCTTTTGCAAGATGGTCCAGAAGTCTCTGGCTCGCCTGATGTTCAATGACTTC
CTGTCAGCCAGCAGTGACACACAAACCAGCTTATATAAGGGGCTGGAGGCTTTCGGGGGG
CTAAAGCTGGAAGACACCTACACCAACAAGGACCTGGATAAAGCACTTCTAAAGGCCTCT
CAGGACATGTTCGACAAGAAAACCAAGGCTTCCCTTTACCTCTCCACTCACAATGGGAAC
ATGTACACCTCATCCCTGTACGGGTGCCTGGCCTCGCTTCTGTCCCACCACTCTGCCCAA
GAACTGGCTGGCTCCAGGATTGGTGCCTTCTCTTATGGCTCTGGTTTAGCAGCAAGTTTC
TTTTCATTTCGAGTATCCCAGGATGCTGCTCCAGGCTCTCCCCTGGACAAGTTGGTGTCC
AGCACATCAGACCTGCCAAAACGCCTAGCCTCCCGAAAGTGTGTGTCTCCTGAGGAGTTC
ACAGAAATAATGAACCAAAGAGAGCAATTCTACCATAAGGTGAATTTCTCCCCACCTGGT
GACACAAACAGCCTTTTCCCAGGTACTTGGTACCTGGAGCGAGTGGACGAGCAGCATCGC
CGAAAGTATGCCCGGCGTCCCGTCTAA
Protein Properties
Number of Residues 508
Molecular Weight 52481.065
Theoretical pI 7.877
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Hydroxymethylglutaryl-CoA synthase, mitochondrial
MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPLAKTDTWPKDVGILALE
VYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLP
WDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLFNAANWM
ESSSWDGRYAMVVCGDIAVYPSGNARPTGGAGAVAMLIGPKAPLALERGLRGTHMENVYD
FYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIF
HTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKAS
QDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSHHSAQELAGSRIGAFSYGSGLAASF
FSFRVSQDAAPGSPLDKLVSSTSDLPKRLASRKCVSPEEFTEIMNQREQFYHKVNFSPPG
DTNSLFPGTWYLERVDEQHRRKYARRPV
GenBank ID Protein 56205097
UniProtKB/Swiss-Prot ID P54868
UniProtKB/Swiss-Prot Entry Name HMCS2_HUMAN
PDB IDs
GenBank Gene ID AL589734
GeneCard ID HMGCS2
GenAtlas ID HMGCS2
HGNC ID HGNC:5008
References
General References
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  3. Mascaro C, Buesa C, Ortiz JA, Haro D, Hegardt FG: Molecular cloning and tissue expression of human mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. Arch Biochem Biophys. 1995 Mar 10;317(2):385-90. [PubMed:7893153 ]
  4. Boukaftane Y, Mitchell GA: Cloning and characterization of the human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase gene. Gene. 1997 Aug 22;195(2):121-6. [PubMed:9305755 ]
  5. Boukaftane Y, Duncan A, Wang S, Labuda D, Robert MF, Sarrazin J, Schappert K, Mitchell GA: Human mitochondrial HMG CoA synthase: liver cDNA and partial genomic cloning, chromosome mapping to 1p12-p13, and possible role in vertebrate evolution. Genomics. 1994 Oct;23(3):552-9. [PubMed:7851882 ]
  6. Camarero N, Mascaro C, Mayordomo C, Vilardell F, Haro D, Marrero PF: 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. 2006 Sep;4(9):645-53. Epub 2006 Aug 28. [PubMed:16940161 ]
  7. Aledo R, Zschocke J, Pie J, Mir C, Fiesel S, Mayatepek E, Hoffmann GF, Casals N, Hegardt FG: Genetic basis of mitochondrial HMG-CoA synthase deficiency. Hum Genet. 2001 Jul;109(1):19-23. [PubMed:11479731 ]
  8. Bouchard L, Robert MF, Vinarov D, Stanley CA, Thompson GN, Morris A, Leonard JV, Quant P, Hsu BY, Boneh A, Boukaftane Y, Ashmarina L, Wang S, Miziorko H, Mitchell GA: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients. Pediatr Res. 2001 Mar;49(3):326-31. [PubMed:11228257 ]
  9. Wolf NI, Rahman S, Clayton PT, Zschocke J: Mitochondrial HMG-CoA synthase deficiency: identification of two further patients carrying two novel mutations. Eur J Pediatr. 2003 Apr;162(4):279-80. Epub 2003 Feb 11. [PubMed:12647205 ]