UniProt Accession

 HCDH_MOUSE; Q61425; Q3TF75; Q3THK8; Q3UFI0; Q8K149; Q925U9 

Genbank Protein ID

 D29639; AF375597; AF375596; AK132260; AK148486; AK167024; AK168238; AK168877; AK169261; BC028833; BC064712 

Genbank Nucleotide ID

 BAA06122.1; AAK54642.1; AAK54642.1; BAE21064.1; BAE28581.1; BAE39197.1; BAE40188.1; BAE40695.1; BAE41023.1; AAH28833.1; AAH64712.1 

Protein Name

 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial 

Protein Synonyms/Alias

 HCDH; Medium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase; Short-chain 3-hydroxyacyl-CoA dehydrogenase 

Gene Name

 Hadh 

Gene Synonyms/Alias

 Hadhsc; Mschad; Schad 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
68	DILAKSKKGIEESLK	acetylation	[1]
75	KGIEESLKRMAKKKF	acetylation	[1, 2, 3]
80	SLKRMAKKKFTENPK	acetylation	[2, 4]
80	SLKRMAKKKFTENPK	succinylation	[4]
81	LKRMAKKKFTENPKA	acetylation	[1, 2, 4, 5, 6, 7]
81	LKRMAKKKFTENPKA	succinylation	[4]
81	LKRMAKKKFTENPKA	succinylation	[4]
87	KKFTENPKAGDEFVE	acetylation	[1, 2, 3, 4, 5]
87	KKFTENPKAGDEFVE	succinylation	[4]
87	KKFTENPKAGDEFVE	succinylation	[4]
95	AGDEFVEKTLSCLST	acetylation	[2, 3, 4]
95	AGDEFVEKTLSCLST	succinylation	[4]
125	EAIVENLKLKNELFQ	acetylation	[2, 4, 5]
125	EAIVENLKLKNELFQ	succinylation	[4]
127	IVENLKLKNELFQRL	acetylation	[2]
136	ELFQRLDKFAAEHTI	acetylation	[2, 3, 4, 7, 8]
136	ELFQRLDKFAAEHTI	succinylation	[4]
136	ELFQRLDKFAAEHTI	ubiquitination	[9]
179	FNPVPMMKLVEVIKT	acetylation	[1, 2, 3, 4]
179	FNPVPMMKLVEVIKT	succinylation	[4]
185	MKLVEVIKTPMTSQK	acetylation	[1, 2, 3, 4, 5, 6, 7, 10]
185	MKLVEVIKTPMTSQK	succinylation	[4]
192	KTPMTSQKTFESLVD	acetylation	[1, 2, 3, 4, 5]
192	KTPMTSQKTFESLVD	succinylation	[4]
202	ESLVDFCKTLGKHPV	acetylation	[1, 2, 3, 4, 5, 11]
202	ESLVDFCKTLGKHPV	succinylation	[4]
206	DFCKTLGKHPVSCKD	acetylation	[2, 4]
206	DFCKTLGKHPVSCKD	succinylation	[4]
212	GKHPVSCKDTPGFIV	acetylation	[1, 2, 3, 4]
212	GKHPVSCKDTPGFIV	succinylation	[4]
212	GKHPVSCKDTPGFIV	ubiquitination	[9]
241	HERGDASKEDIDTAM	acetylation	[1, 2, 3, 4, 5, 7, 8, 12]
241	HERGDASKEDIDTAM	succinylation	[4]
249	EDIDTAMKLGAGYPM	acetylation	[5]
300	MNNLVAQKKLGKKTG	acetylation	[1, 2]
312	KTGEGFYKYK*****	acetylation	[1, 2, 3, 4]
312	KTGEGFYKYK*****	succinylation	[4]

Reference

 [1] 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]
 [2] 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]
 [3] 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]
 [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] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] 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] 

Functional Description

 Plays an essential role in the mitochondrial beta- oxidation of short chain fatty acids. Exerts it highest activity toward 3-hydroxybutyryl-CoA. 

Sequence Annotation

 NP_BIND 34 39 NAD (By similarity).
 BINDING 57 57 NAD (By similarity).
 BINDING 73 73 Coenzyme A (By similarity).
 BINDING 80 80 Coenzyme A (By similarity).
 BINDING 122 122 NAD (By similarity).
 BINDING 127 127 NAD (By similarity).
 BINDING 149 149 Coenzyme A (By similarity).
 BINDING 149 149 NAD (By similarity).
 BINDING 173 173 NAD (By similarity).
 BINDING 305 305 NAD (By similarity).
 MOD_RES 185 185 N6-acetyllysine (By similarity).
 MOD_RES 202 202 N6-acetyllysine.
 MOD_RES 241 241 N6-acetyllysine (By similarity).
 MOD_RES 312 312 N6-acetyllysine (By similarity).  

Keyword

 Acetylation; Complete proteome; Fatty acid metabolism; Lipid metabolism; Mitochondrion; NAD; Oxidoreductase; Reference proteome; Transit peptide. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 314 AA 

Protein Sequence

Gene Ontology

 GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
 GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
 GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IDA:MGI.
 GO:0070403; F:NAD+ binding; IEA:InterPro.
 GO:0006635; P:fatty acid beta-oxidation; IEA:UniProtKB-UniPathway.
 GO:0046676; P:negative regulation of insulin secretion; IEA:Compara.
 GO:0014823; P:response to activity; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0032868; P:response to insulin stimulus; IEA:Compara. 

Interpro

 IPR022694; 3-OHacyl-CoA_DH.
 IPR006180; 3-OHacyl-CoA_DH_CS.
 IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
 IPR006108; 3HC_DH_C.
 IPR008927; 6-PGluconate_DH_C-like.
 IPR013328; DH_multihelical.
 IPR016040; NAD(P)-bd_dom. 

Pfam

 PF00725; 3HCDH
 PF02737; 3HCDH_N 

SMART

  

PROSITE

 PS00067; 3HCDH 

PRINTS