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Identification
HMDB Protein ID HMDBP00053
Secondary Accession Numbers
  • 5282
Name Hydroxymethylglutaryl-CoA synthase, cytoplasmic
Synonyms
  1. 3-hydroxy-3-methylglutaryl coenzyme A synthase
  2. HMG-CoA synthase
Gene Name HMGCS1
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
  • Alendronate Action Pathway
  • Atorvastatin Action Pathway
  • Butanoate metabolism
  • Cerivastatin Action Pathway
  • CHILD Syndrome
  • Cholesteryl ester storage disease
  • Chondrodysplasia Punctata II, X Linked Dominant (CDPX2)
  • Desmosterolosis
  • Fluvastatin Action Pathway
  • Hyper-IgD syndrome
  • Hypercholesterolemia
  • Ibandronate Action Pathway
  • Lovastatin Action Pathway
  • Lysosomal Acid Lipase Deficiency (Wolman Disease)
  • Mevalonic aciduria
  • Pamidronate Action Pathway
  • Pravastatin Action Pathway
  • Risedronate Action Pathway
  • Rosuvastatin Action Pathway
  • Simvastatin Action Pathway
  • Smith-Lemli-Opitz Syndrome (SLOS)
  • Steroid Biosynthesis
  • Synthesis and degradation of ketone bodies
  • Terpenoid backbone biosynthesis
  • Valine, leucine and isoleucine degradation
  • Wolman disease
  • Zoledronate Action Pathway
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
cellular response to follicle-stimulating hormone stimulus
cholesterol biosynthetic process
cellular response to cholesterol
liver development
response to drug
response to purine-containing compound
brain development
response to acid
male gonad development
response to lipoprotein particle stimulus
response to low light intensity stimulus
response to tellurium ion
cellular lipid metabolic process
response to vitamin E
Cellular Component
cytosol
plasma membrane
nucleus
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
drug binding
hydroxymethylglutaryl-CoA synthase activity
organic acid binding
isomerase activity
Process
metabolic process
primary metabolic process
lipid metabolic process
cellular lipid metabolic process
isoprenoid metabolic process
isoprenoid biosynthetic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 5
Locus 5p14-p13
SNPs HMGCS1
Gene Sequence
>1563 bp
ATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTGGGAATTGTT
GCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAAATATGAT
GGTGTAGATGCTGGAAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACA
GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAAT
AACCTTTCCTATGATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAA
TCAAAGTCTGTGAAGACTAATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATA
GAAGGAATCGACACAACTAATGCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTT
AACTGGATTGAGTCCAGCTCTTGGGATGGACGGTATGCCCTGGTAGTTGCAGGAGATATT
GCTGTATATGCCACAGGAAATGCTAGACCTACAGGTGGAGTTGGAGCAGTAGCTCTGCTA
ATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGTGGGACACATATGCAACAT
GCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGAAAACTC
TCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAAGATC
CATGCCCAGTGGCAGAAAGAGGCAAATGATAACGATTTTACCTTGAATGATTTTGGCTTC
ATGATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTG
AATGACTTCCTTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGAAGGCC
TTTGGGGATGTTAAGTTAGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATG
AAGGCTAGCTCTGAACTCTTCAGTCAGAAAACAAAGGCATCTTTACTTGTATCAAATCAA
AATGGAAATATGTACACATCTTCAGTATATGGTTCCCTTGCATCTGTTCTAGCACAGTAC
TCACCTCAGCATTTAGCAGGGAAGAGAATTGGAGTGTTTTCTTATGGTTCTGGTTTGGCT
GCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTGCTCTTGATAAA
ATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCACAA
GATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATATT
CCCCAGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAA
AAGCACAGAAGAACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGA
GTAGGACTTGTGCATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTA
CCAAGACTCCCTGCTACAGCAGCAGAACCTGAAGCAGCAGTTATTAGTAATGGGGTATGG
TAA
Protein Properties
Number of Residues 520
Molecular Weight 57293.105
Theoretical pI 5.412
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Hydroxymethylglutaryl-CoA synthase, cytoplasmic
MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCT
DREDINSLCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDI
EGIDTTNACYGGTAAVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALL
IGPNAPLIFERGLRGTHMQHAYDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKI
HAQWQKEGNDKDFTLNDFGFMIFHSPYCKLVQKSLARMLLNDFLNDQNRDKNSIYSGLEA
FGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASLLVSNQNGNMYTSSVYGSLASVLAQY
SPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKITASLCDLKSRLDSRTGVAP
DVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARRPTPNDDTLDEG
VGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
GenBank ID Protein 30009
UniProtKB/Swiss-Prot ID Q01581
UniProtKB/Swiss-Prot Entry Name HMCS1_HUMAN
PDB IDs
GenBank Gene ID X66435
GeneCard ID HMGCS1
GenAtlas ID HMGCS1
HGNC ID HGNC:5007
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  6. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  7. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  8. Russ AP, Ruzicka V, Maerz W, Appelhans H, Gross W: Amplification and direct sequencing of a cDNA encoding human cytosolic 3-hydroxy-3-methylglutaryl-coenzyme A synthase. Biochim Biophys Acta. 1992 Oct 20;1132(3):329-31. [PubMed:1358203 ]
  9. Rokosz LL, Boulton DA, Butkiewicz EA, Sanyal G, Cueto MA, Lachance PA, Hermes JD: Human cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase: expression, purification, and characterization of recombinant wild-type and Cys129 mutant enzymes. Arch Biochem Biophys. 1994 Jul;312(1):1-13. [PubMed:7913309 ]