UniProt Accession

 ECHA_MOUSE; Q8BMS1; Q3TCY3; Q5U5Y5; Q8QZU4 

Genbank Protein ID

 AK029017; AK170478; AK170683; BC027156; BC037009; BC046978; BC058569 

Genbank Nucleotide ID

 BAC26245.1; BAE41822.1; BAE41956.1; AAH27156.1; AAH37009.1; AAH46978.1; AAH58569.1 

Protein Name

 Trifunctional enzyme subunit alpha, mitochondrial 

Protein Synonyms/Alias

 TP-alpha; Long-chain enoyl-CoA hydratase; Long chain 3-hydroxyacyl-CoA dehydrogenase 

Gene Name

 Hadha 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
46	THINYGVKGDVAVIR	acetylation	[1, 2, 3, 4]
46	THINYGVKGDVAVIR	succinylation	[3]
46	THINYGVKGDVAVIR	ubiquitination	[5]
60	RINSPNSKVNTLNKE	acetylation	[1, 2, 3, 4, 6]
60	RINSPNSKVNTLNKE	succinylation	[3]
60	RINSPNSKVNTLNKE	ubiquitination	[5]
66	SKVNTLNKEVQSEFI	acetylation	[6]
129	EGQRMFEKLEKSPKP	acetylation	[1, 2, 3, 4, 7, 8]
129	EGQRMFEKLEKSPKP	succinylation	[3]
163	CQYRIATKDRKTVLG	acetylation	[1, 4]
166	RIATKDRKTVLGVPE	acetylation	[2, 3, 6]
166	RIATKDRKTVLGVPE	succinylation	[3]
166	RIATKDRKTVLGVPE	ubiquitination	[5]
190	GGTQRLPKMVGVPAA	ubiquitination	[5]
213	NIRADRAKKMGLVDQ	acetylation	[2, 3]
213	NIRADRAKKMGLVDQ	succinylation	[3]
214	IRADRAKKMGLVDQL	acetylation	[2, 3, 6]
214	IRADRAKKMGLVDQL	phosphoglycerylation	[9]
214	IRADRAKKMGLVDQL	succinylation	[3]
214	IRADRAKKMGLVDQL	succinylation	[3]
214	IRADRAKKMGLVDQL	ubiquitination	[5]
230	EPLGPGIKSPEERTI	acetylation	[1, 2, 3]
230	EPLGPGIKSPEERTI	succinylation	[3]
249	EVAVNFAKGLADRKV	acetylation	[2, 3]
249	EVAVNFAKGLADRKV	succinylation	[3]
267	QSKGLVEKLTTYAMT	acetylation	[2]
289	VYKTVEEKVKKQTKG	acetylation	[1, 2, 4, 10]
291	KTVEEKVKKQTKGLY	acetylation	[1, 2]
295	EKVKKQTKGLYPAPL	acetylation	[1, 2, 3, 4]
295	EKVKKQTKGLYPAPL	succinylation	[3]
295	EKVKKQTKGLYPAPL	ubiquitination	[5]
303	GLYPAPLKIIDAVKA	acetylation	[1, 2, 3, 4, 6, 11]
303	GLYPAPLKIIDAVKA	succinylation	[3]
303	GLYPAPLKIIDAVKA	ubiquitination	[5]
309	LKIIDAVKAGLEQGS	acetylation	[2]
309	LKIIDAVKAGLEQGS	ubiquitination	[5]
326	GYLAESQKFGELALT	acetylation	[1, 2, 3, 4, 6, 7, 8, 12, 13]
326	GYLAESQKFGELALT	succinylation	[3]
326	GYLAESQKFGELALT	ubiquitination	[5]
334	FGELALTKESKALMG	acetylation	[1, 2, 3]
334	FGELALTKESKALMG	succinylation	[3]
337	LALTKESKALMGLYN	acetylation	[1, 4]
350	YNGQVLCKKNKFGAP	acetylation	[1, 2, 3, 4, 6, 7, 12]
350	YNGQVLCKKNKFGAP	succinylation	[3]
350	YNGQVLCKKNKFGAP	ubiquitination	[5]
351	NGQVLCKKNKFGAPQ	acetylation	[1]
353	QVLCKKNKFGAPQKN	acetylation	[1, 2, 3, 4, 6]
353	QVLCKKNKFGAPQKN	succinylation	[3]
386	VSVDKGLKTLLKDTT	acetylation	[1, 2, 4]
390	KGLKTLLKDTTVTGL	acetylation	[1, 3, 4, 6]
390	KGLKTLLKDTTVTGL	succinylation	[3]
390	KGLKTLLKDTTVTGL	ubiquitination	[5]
406	RGQQQVFKGLNDKVK	acetylation	[1, 2, 3, 4, 6, 8, 10, 11, 12, 13]
406	RGQQQVFKGLNDKVK	succinylation	[3]
406	RGQQQVFKGLNDKVK	succinylation	[3]
406	RGQQQVFKGLNDKVK	ubiquitination	[5]
411	VFKGLNDKVKKKALT	acetylation	[1, 2, 3, 4, 10]
411	VFKGLNDKVKKKALT	succinylation	[3]
411	VFKGLNDKVKKKALT	succinylation	[3]
413	KGLNDKVKKKALTSF	acetylation	[1, 2, 4, 10]
414	GLNDKVKKKALTSFE	acetylation	[1, 2, 3]
414	GLNDKVKKKALTSFE	succinylation	[3]
415	LNDKVKKKALTSFER	acetylation	[2, 3]
415	LNDKVKKKALTSFER	succinylation	[3]
415	LNDKVKKKALTSFER	succinylation	[3]
415	LNDKVKKKALTSFER	ubiquitination	[5]
436	LIGQLDYKGFEKADM	acetylation	[1, 2, 3, 4, 6, 8, 10]
436	LIGQLDYKGFEKADM	succinylation	[3]
440	LDYKGFEKADMVIEA	acetylation	[3]
440	LDYKGFEKADMVIEA	succinylation	[3]
455	VFEDLGVKHKVLKEV	ubiquitination	[5]
457	EDLGVKHKVLKEVES	acetylation	[1]
460	GVKHKVLKEVESVTP	acetylation	[1, 2, 3, 4, 6, 11]
460	GVKHKVLKEVESVTP	succinylation	[3]
493	AVSKRPEKVIGMHYF	acetylation	[1]
505	HYFSPVDKMQLLEII	acetylation	[1, 2, 3, 4, 6, 13]
505	HYFSPVDKMQLLEII	succinylation	[3]
516	LEIITTDKTSKDTTA	acetylation	[1, 3, 4]
516	LEIITTDKTSKDTTA	succinylation	[3]
519	ITTDKTSKDTTASAV	acetylation	[1, 2, 3, 4, 6]
519	ITTDKTSKDTTASAV	succinylation	[3]
519	ITTDKTSKDTTASAV	ubiquitination	[5]
540	GKVIIVVKDGPGFYT	acetylation	[1, 2, 4, 6, 11]
540	GKVIIVVKDGPGFYT	ubiquitination	[5]
569	LQEGVDPKKLDALTT	acetylation	[1, 2, 3, 4, 6, 7]
569	LQEGVDPKKLDALTT	succinylation	[3]
569	LQEGVDPKKLDALTT	ubiquitination	[5]
570	QEGVDPKKLDALTTG	acetylation	[6]
620	GGSVELLKQMVSKGF	acetylation	[1, 2, 3, 10]
620	GGSVELLKQMVSKGF	succinylation	[3]
620	GGSVELLKQMVSKGF	ubiquitination	[5]
625	LLKQMVSKGFLGRKS	acetylation	[1, 2]
634	FLGRKSGKGFYIYQE	acetylation	[1, 2, 3]
634	FLGRKSGKGFYIYQE	succinylation	[3]
644	YIYQEGSKNKSLNSE	acetylation	[1, 2, 3, 4, 6, 12]
644	YIYQEGSKNKSLNSE	succinylation	[3]
644	YIYQEGSKNKSLNSE	ubiquitination	[5]
646	YQEGSKNKSLNSEMD	acetylation	[3]
646	YQEGSKNKSLNSEMD	succinylation	[3]
646	YQEGSKNKSLNSEMD	ubiquitination	[5]
664	ANLRLPAKPEVSSDE	acetylation	[1, 2, 3, 4, 6]
664	ANLRLPAKPEVSSDE	succinylation	[3]
664	ANLRLPAKPEVSSDE	ubiquitination	[5]
728	VDLYGAQKVVDRLRK	acetylation	[1, 2, 3, 4, 6, 7, 10, 11, 12]
728	VDLYGAQKVVDRLRK	succinylation	[3]
728	VDLYGAQKVVDRLRK	ubiquitination	[5]
735	KVVDRLRKYESAYGT	acetylation	[2, 11]
735	KVVDRLRKYESAYGT	ubiquitination	[5]
759	DHANNSSKKFYQ***	acetylation	[1, 2, 3, 4]
759	DHANNSSKKFYQ***	succinylation	[3]
759	DHANNSSKKFYQ***	ubiquitination	[5]

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] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] Functional lysine modification by an intrinsically reactive primary glycolytic metabolite.
 Moellering RE, Cravatt BF.
 Science. 2013 Aug 2;341(6145):549-53. [PMID: 23908237]
 [10] 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]
 [11] 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]
 [12] 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]
 [13] 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] 

Functional Description

 Bifunctional subunit. 

Sequence Annotation

 MOD_RES 129 129 N6-acetyllysine.
 MOD_RES 295 295 N6-acetyllysine (By similarity).
 MOD_RES 303 303 N6-acetyllysine (By similarity).
 MOD_RES 326 326 N6-acetyllysine.
 MOD_RES 350 350 N6-acetyllysine.
 MOD_RES 406 406 N6-acetyllysine (By similarity).
 MOD_RES 505 505 N6-acetyllysine (By similarity).
 MOD_RES 540 540 N6-acetyllysine (By similarity).
 MOD_RES 569 569 N6-acetyllysine.
 MOD_RES 644 644 N6-acetyllysine (By similarity).
 MOD_RES 728 728 N6-acetyllysine.  

Keyword

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

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 763 AA 

Protein Sequence

Gene Ontology

 GO:0016507; C:mitochondrial fatty acid beta-oxidation multienzyme complex; IEA:Compara.
 GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
 GO:0042645; C:mitochondrial nucleoid; IEA:Compara.
 GO:0005730; C:nucleolus; IEA:Compara.
 GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IEA:Compara.
 GO:0003988; F:acetyl-CoA C-acyltransferase activity; IEA:Compara.
 GO:0004300; F:enoyl-CoA hydratase activity; TAS:MGI.
 GO:0000062; F:fatty-acyl-CoA binding; IEA:Compara.
 GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; IDA:MGI.
 GO:0016508; F:long-chain-enoyl-CoA hydratase activity; IEA:Compara.
 GO:0051287; F:NAD binding; IEA:Compara.
 GO:0006635; P:fatty acid beta-oxidation; IMP:MGI.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0032868; P:response to insulin stimulus; IMP:MGI. 

Interpro

 IPR006180; 3-OHacyl-CoA_DH_CS.
 IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
 IPR006108; 3HC_DH_C.
 IPR008927; 6-PGluconate_DH_C-like.
 IPR001753; Crotonase_core_superfam.
 IPR013328; DH_multihelical.
 IPR018376; Enoyl-CoA_hyd/isom_CS.
 IPR012803; Fa_ox_alpha_mit.
 IPR016040; NAD(P)-bd_dom. 

Pfam

 PF00725; 3HCDH
 PF02737; 3HCDH_N
 PF00378; ECH 

SMART

  

PROSITE

 PS00067; 3HCDH
 PS00166; ENOYL_COA_HYDRATASE 

PRINTS