UniProt Accession

 HMCS2_MOUSE; P54869; Q64740; Q9DBK1; Q9DBM4 

Genbank Protein ID

 AK004865; AK004902; BC014714; BC024744; U12790; U12791 

Genbank Nucleotide ID

 BAB23626.1; BAB23657.1; AAH14714.1; AAH24744.1; AAA92675.1; AAA92676.1 

Protein Name

 Hydroxymethylglutaryl-CoA synthase, mitochondrial 

Protein Synonyms/Alias

 HMG-CoA synthase; 3-hydroxy-3-methylglutaryl coenzyme A synthase 

Gene Name

 Hmgcs2 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
46	IPPAPLAKTDTWPKD	acetylation	[1]
46	IPPAPLAKTDTWPKD	ubiquitination	[2]
52	AKTDTWPKDVGILAL	acetylation	[3, 4]
52	AKTDTWPKDVGILAL	succinylation	[4]
75	VDQTDLEKFNNVEAG	acetylation	[1]
83	FNNVEAGKYTVGLGQ	acetylation	[1, 3, 4, 5, 6, 7, 8, 9]
83	FNNVEAGKYTVGLGQ	succinylation	[4]
83	FNNVEAGKYTVGLGQ	ubiquitination	[2]
118	QRLMERTKLPWDAVG	acetylation	[1, 3, 4, 6, 7, 8, 9, 10]
118	QRLMERTKLPWDAVG	succinylation	[4]
118	QRLMERTKLPWDAVG	ubiquitination	[2]
137	GTETIIDKSKAVKTV	acetylation	[1, 7, 9]
137	GTETIIDKSKAVKTV	ubiquitination	[2]
221	VAMLIGPKAPLVLEQ	acetylation	[1, 4]
221	VAMLIGPKAPLVLEQ	succinylation	[4]
221	VAMLIGPKAPLVLEQ	ubiquitination	[2]
243	ENAYDFYKPNLASEY	acetylation	[1, 3, 4, 6, 7, 8, 9, 10]
243	ENAYDFYKPNLASEY	succinylation	[4]
243	ENAYDFYKPNLASEY	ubiquitination	[2]
256	EYPLVDGKLSIQCYL	acetylation	[1, 4, 9]
256	EYPLVDGKLSIQCYL	succinylation	[4]
282	KKIQNQWKQAGNNQP	acetylation	[9]
306	IFHTPFCKMVQKSLA	acetylation	[1, 7, 9, 10]
310	PFCKMVQKSLARLMF	acetylation	[1, 3, 4, 7, 9, 10]
310	PFCKMVQKSLARLMF	succinylation	[4]
310	PFCKMVQKSLARLMF	ubiquitination	[2]
327	FLSSSSDKQNNLYKG	acetylation	[1, 4, 7, 9]
327	FLSSSSDKQNNLYKG	succinylation	[4]
327	FLSSSSDKQNNLYKG	ubiquitination	[2]
333	DKQNNLYKGLEAFRG	acetylation	[1, 4, 6, 7, 9, 10]
333	DKQNNLYKGLEAFRG	succinylation	[4]
333	DKQNNLYKGLEAFRG	ubiquitination	[2]
342	LEAFRGLKLEETYTN	acetylation	[1, 4, 7, 9]
342	LEAFRGLKLEETYTN	succinylation	[4]
342	LEAFRGLKLEETYTN	ubiquitination	[2]
350	LEETYTNKDVDKALL	acetylation	[1, 3, 4, 6, 7, 9, 10]
350	LEETYTNKDVDKALL	succinylation	[4]
350	LEETYTNKDVDKALL	ubiquitination	[2]
354	YTNKDVDKALLKASL	acetylation	[1, 3, 4, 6, 7, 8, 9, 10]
354	YTNKDVDKALLKASL	succinylation	[4]
354	YTNKDVDKALLKASL	succinylation	[4]
354	YTNKDVDKALLKASL	ubiquitination	[2]
358	DVDKALLKASLDMFN	acetylation	[1, 3, 4, 7, 9]
358	DVDKALLKASLDMFN	succinylation	[4]
358	DVDKALLKASLDMFN	ubiquitination	[2]
367	SLDMFNQKTKASLYL	acetylation	[7, 9]
367	SLDMFNQKTKASLYL	ubiquitination	[2]
427	FFSFRVSKDASPGSP	acetylation	[1, 3, 5, 6, 7, 9, 10]
427	FFSFRVSKDASPGSP	ubiquitination	[2]
437	SPGSPLEKLVSSVSD	acetylation	[1, 3, 5, 6, 7, 9, 10]
437	SPGSPLEKLVSSVSD	ubiquitination	[2]
447	SSVSDLPKRLDSRRR	acetylation	[1, 3, 4, 6, 7, 8, 9, 10]
447	SSVSDLPKRLDSRRR	succinylation	[4]
447	SSVSDLPKRLDSRRR	ubiquitination	[2]
473	QREQFYHKVNFSPPG	acetylation	[1, 4, 7, 9, 10]
473	QREQFYHKVNFSPPG	succinylation	[4]
473	QREQFYHKVNFSPPG	ubiquitination	[2]

Reference

 [1] Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.
 Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, Gibson BW.
 Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6. [PMID: 23576753]
 [2] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [3] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
 Simon GM, Cheng J, Gordon JI.
 Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
 [4] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [5] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [6] Mitochondrial acetylome analysis in a mouse model of alcohol-induced liver injury utilizing SIRT3 knockout mice.
 Fritz KS, Galligan JJ, Hirschey MD, Verdin E, Petersen DR.
 J Proteome Res. 2012 Mar 2;11(3):1633-43. [PMID: 22309199]
 [7] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
 Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
 Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
 [8] Circadian acetylome reveals regulation of mitochondrial metabolic pathways.
 Masri S, Patel VR, Eckel-Mahan KL, Peleg S, Forne I, Ladurner AG, Baldi P, Imhof A, Sassone-Corsi P.
 Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3339-44. [PMID: 23341599]
 [9] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
 Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
 J Biol Chem. 2013 Jul 17;. [PMID: 23864654]
 [10] SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production.
 Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP, Verdin E.
 Cell Metab. 2010 Dec 1;12(6):654-61. [PMID: 21109197] 

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 132 132 Proton donor/acceptor (By similarity).
 ACT_SITE 166 166 Nucleophile (By similarity).
 ACT_SITE 301 301 Proton donor/acceptor (By similarity).
 BINDING 80 80 Substrate (By similarity).
 BINDING 204 204 Substrate (By similarity).
 BINDING 258 258 Substrate (By similarity).
 BINDING 380 380 Substrate (By similarity).
 MOD_RES 83 83 N6-acetyllysine.
 MOD_RES 310 310 N6-succinyllysine (By similarity).
 MOD_RES 427 427 N6-acetyllysine.
 MOD_RES 433 433 Phosphoserine.
 MOD_RES 437 437 N6-acetyllysine.  

Keyword

 Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Complete proteome; Lipid biosynthesis; Lipid metabolism; Mitochondrion; Phosphoprotein; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase; Transit peptide. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 508 AA 

Protein Sequence

Gene Ontology

 GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
 GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IEA:EC.
 GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
 GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro. 

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