CPLM-006825

Genbank Nucleotide ID

Hydroxymethylglutaryl-CoA lyase, mitochondrial

Protein Synonyms/Alias

HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase

Mus musculus (Mouse)

Position	Peptide	Type	References
48	RDGLQNEKSIVPTPV	acetylation	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]
48	RDGLQNEKSIVPTPV	succinylation	[10]
80	ATSFVSPKWVPQMAD	acetylation	[9]
93	ADHSDVLKGIQKFPG	acetylation	[6, 11]
97	DVLKGIQKFPGINYP	ubiquitination	[12]
111	PVLTPNMKGFEEAVA	acetylation	[9, 11]
137	VSELFTRKNANCSIE	acetylation	[9, 10]
137	VSELFTRKNANCSIE	succinylation	[10]
137	VSELFTRKNANCSIE	ubiquitination	[12]
179	LGCPYEGKVSPAKVA	acetylation	[4, 6, 9, 10, 11]
179	LGCPYEGKVSPAKVA	succinylation	[10]
190	AKVAEVAKKLYSMGC	acetylation	[6, 11]
324	KVAQATCKL******	acetylation	[9]

[1] 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]
[2] The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching.
Yang L, Vaitheesvaran B, Hartil K, Robinson AJ, Hoopmann MR, Eng JK, Kurland IJ, Bruce JE.
J Proteome Res. 2011 Sep 2;10(9):4134-49. [PMID: 21728379]
[3] 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]
[4] 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]
[5] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
[6] 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]
[7] 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]
[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] 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]
[10] 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]
[11] 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]
[12] 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]

Functional Description

Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism. Ketone bodies (beta- hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism (By similarity).

MOTIF 323 325 Microbody targeting signal (Potential).
ACT_SITE 266 266 By similarity.
METAL 42 42 Divalent metal cation (By similarity).
METAL 233 233 Divalent metal cation (By similarity).
METAL 235 235 Divalent metal cation (By similarity).
METAL 275 275 Divalent metal cation (By similarity).
BINDING 41 41 Substrate (By similarity).
MOD_RES 48 48 N6-acetyllysine.
DISULFID 323 323 Interchain (By similarity).

Acetylation; Complete proteome; Disulfide bond; Lyase; Metal-binding; Mitochondrion; Peroxisome; Reference proteome; Transit peptide.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
GO:0031406; F:carboxylic acid binding; IEA:Compara.
GO:0000062; F:fatty-acyl-CoA binding; IEA:Compara.
GO:0004419; F:hydroxymethylglutaryl-CoA lyase activity; ISS:UniProtKB.
GO:0000287; F:magnesium ion binding; IEA:Compara.
GO:0030145; F:manganese ion binding; IEA:Compara.
GO:0046872; F:metal ion binding; ISS:UniProtKB.
GO:0006637; P:acyl-CoA metabolic process; IEA:Compara.
GO:0009790; P:embryo development; IMP:MGI.
GO:0046951; P:ketone body biosynthetic process; ISS:UniProtKB.
GO:0001889; P:liver development; IEA:Compara.
GO:0007005; P:mitochondrion organization; IMP:MGI.
GO:0051262; P:protein tetramerization; IEA:Compara.
GO:0070542; P:response to fatty acid; IEA:Compara.
GO:0007584; P:response to nutrient; IEA:Compara.
GO:0042594; P:response to starvation; IEA:Compara.

IPR013785; Aldolase_TIM.
IPR027167; HMG-CoA_lyase.
IPR000138; HMG_CoA_lyase_AS.
IPR000891; PYR_CT.

PS01062; HMG_COA_LYASE
PS50991; PYR_CT