CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010863
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Hydroxymethylglutaryl-CoA synthase, cytoplasmic 
Protein Synonyms/Alias
 HMG-CoA synthase; 3-hydroxy-3-methylglutaryl coenzyme A synthase 
Gene Name
 HMGCS1 
Gene Synonyms/Alias
 HMGCS 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
46YDGVDAGKYTIGLGQacetylation[1]
46YDGVDAGKYTIGLGQubiquitination[2, 3, 4, 5, 6]
100GTETIIDKSKSVKTNubiquitination[2, 3, 5, 6, 7]
206QHAYDFYKPDMLSEYacetylation[8, 9, 10]
206QHAYDFYKPDMLSEYubiquitination[3, 5]
238RCYSVYCKKIHAQWQubiquitination[5]
239CYSVYCKKIHAQWQKubiquitination[5]
246KIHAQWQKEGNDKDFacetylation[1]
246KIHAQWQKEGNDKDFubiquitination[3]
273PYCKLVQKSLARMLLacetylation[1]
273PYCKLVQKSLARMLLubiquitination[2, 5, 6, 7, 10]
291LNDQNRDKNSIYSGLubiquitination[2, 3, 4, 5, 6, 10]
305LEAFGDVKLEDTYFDubiquitination[5]
317YFDRDVEKAFMKASSacetylation[9, 10]
317YFDRDVEKAFMKASSubiquitination[2, 3, 5, 6, 10]
321DVEKAFMKASSELFSacetylation[1, 8]
321DVEKAFMKASSELFSubiquitination[2, 3, 4, 5, 6, 7, 10]
330SSELFSQKTKASLLVubiquitination[3, 5, 7, 10]
332ELFSQKTKASLLVSNubiquitination[5]
400TPGSALDKITASLCDubiquitination[2, 5, 6, 10]
409TASLCDLKSRLDSRTubiquitination[2, 5, 6, 10]
428DVFAENMKLREDTHHubiquitination[3, 4, 5, 7, 10, 11]
461YLVRVDEKHRRTYARubiquitination[12]
498EHIPSPAKKVPRLPAubiquitination[3, 5]
499HIPSPAKKVPRLPATubiquitination[5]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [8] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [11] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [12] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
Functional Description
 This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase. 
Sequence Annotation
 ACT_SITE 129 129
 MOD_RES 4 4 Phosphoserine.
 MOD_RES 46 46 N6-acetyllysine.
 MOD_RES 273 273 N6-acetyllysine.
 MOD_RES 476 476 Phosphothreonine.
 MOD_RES 495 495 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Complete proteome; Cytoplasm; Lipid biosynthesis; Lipid metabolism; Phosphoprotein; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 520 AA 
Protein Sequence
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQAKMGFCT 60
DREDINSLCM TVVQNLMERN NLSYDCIGRL EVGTETIIDK SKSVKTNLMQ LFEESGNTDI 120
EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVVAGDI AVYATGNARP TGGVGAVALL 180
IGPNAPLIFE RGLRGTHMQH AYDFYKPDML SEYPIVDGKL SIQCYLSALD RCYSVYCKKI 240
HAQWQKEGND KDFTLNDFGF MIFHSPYCKL VQKSLARMLL NDFLNDQNRD KNSIYSGLEA 300
FGDVKLEDTY FDRDVEKAFM KASSELFSQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY 360
SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK ITASLCDLKS RLDSRTGVAP 420
DVFAENMKLR EDTHHLVNYI PQGSIDSLFE GTWYLVRVDE KHRRTYARRP TPNDDTLDEG 480
VGLVHSNIAT EHIPSPAKKV PRLPATAAEP EAAVISNGEH 520 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0008144; F:drug binding; IEA:Compara.
 GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; TAS:ProtInc.
 GO:0016853; F:isomerase activity; IEA:Compara.
 GO:0043177; F:organic acid binding; IEA:Compara.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
 GO:0071397; P:cellular response to cholesterol; IEA:Compara.
 GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Compara.
 GO:0006695; P:cholesterol biosynthetic process; TAS:Reactome.
 GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
 GO:0001889; P:liver development; IEA:Compara.
 GO:0008584; P:male gonad development; IEA:Compara.
 GO:0001101; P:response to acid; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0055094; P:response to lipoprotein particle stimulus; IEA:Compara.
 GO:0009645; P:response to low light intensity stimulus; IEA:Compara.
 GO:0014074; P:response to purine-containing compound; IEA:Compara.
 GO:0046690; P:response to tellurium ion; IEA:Compara.
 GO:0033197; P:response to vitamin E; IEA:Compara. 
Interpro
 IPR000590; HMG_CoA_synt_AS.
 IPR013746; HMG_CoA_synt_C.
 IPR013528; HMG_CoA_synth_N.
 IPR010122; HMG_CoA_synthase_euk.
 IPR016039; Thiolase-like.
 IPR016038; Thiolase-like_subgr. 
Pfam
 PF08540; HMG_CoA_synt_C
 PF01154; HMG_CoA_synt_N 
SMART
  
PROSITE
 PS01226; HMG_COA_SYNTHASE 
PRINTS