CPLM-008916

Genbank Nucleotide ID

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Protein Synonyms/Alias

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

Homo sapiens (Human)

Position	Peptide	Type	References
83	YNNVEAGKYTVGLGQ	acetylation	[1]
137	GTETIIDKSKAVKTV	ubiquitination	[2, 3, 4]
276	CYTSYRKKIQNQWKQ	methylation	[5]

[1] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[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] 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]
[4] 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]
[5] Large-scale global identification of protein lysine methylation in vivo.
Cao XJ, Arnaudo AM, Garcia BA.
Epigenetics. 2013 May 1;8(5):477-85. [PMID: 23644510]

Functional Description

This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

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

3D-structure; Acetylation; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Complete proteome; Disease mutation; Lipid biosynthesis; Lipid metabolism; Mitochondrion; Phosphoprotein; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase; Transit peptide.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005743; C:mitochondrial inner membrane; IEA:Compara.
GO:0005759; C:mitochondrial matrix; TAS:Reactome.
GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IEA:EC.
GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
GO:0046951; P:ketone body biosynthetic process; TAS:Reactome.

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.

PF08540; HMG_CoA_synt_C
PF01154; HMG_CoA_synt_N

PS01226; HMG_COA_SYNTHASE