UniProt Accession

 DLDH_MOUSE; O08749; Q3TG55; Q3U5W5; Q3UWP7; Q99LD3 

Genbank Protein ID

 U73445; AK117104; AK136193; AK153399; AK168875; BC003368 

Genbank Nucleotide ID

 AAC53170.1; BAE43405.1; BAE22867.1; BAE31961.1; BAE40693.1; AAH03368.1 

Protein Name

 Dihydrolipoyl dehydrogenase, mitochondrial 

Protein Synonyms/Alias

 Dihydrolipoamide dehydrogenase 

Gene Name

 Dld 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
66	KSAQLGFKTVCIEKN	acetylation	[1, 2, 3, 4, 5, 6, 7, 8]
66	KSAQLGFKTVCIEKN	succinylation	[7]
72	FKTVCIEKNETLGGT	acetylation	[8]
104	YYHMAHGKDFASRGI	acetylation	[3, 4, 5, 6, 7, 8]
104	YYHMAHGKDFASRGI	succinylation	[7]
122	EVRLNLEKMMEQKHS	acetylation	[1, 2, 3, 4, 5, 6, 7, 8]
122	EVRLNLEKMMEQKHS	succinylation	[7]
127	LEKMMEQKHSAVKAL	acetylation	[3, 4, 8, 9]
132	EQKHSAVKALTGGIA	acetylation	[1, 3, 6, 7, 8]
132	EQKHSAVKALTGGIA	succinylation	[7]
143	GGIAHLFKQNKVVHV	acetylation	[1, 2, 3, 4, 6, 7, 8]
143	GGIAHLFKQNKVVHV	succinylation	[7]
143	GGIAHLFKQNKVVHV	ubiquitination	[10]
146	AHLFKQNKVVHVNGF	acetylation	[1, 4, 6, 8]
155	VHVNGFGKITGKNQV	acetylation	[4, 6, 7, 8]
155	VHVNGFGKITGKNQV	succinylation	[7]
159	GFGKITGKNQVTATK	acetylation	[2, 6, 7]
159	GFGKITGKNQVTATK	succinylation	[7]
166	KNQVTATKADGSTQV	acetylation	[7]
166	KNQVTATKADGSTQV	succinylation	[7]
271	ILQRQGFKFKLNTKV	acetylation	[4, 8]
273	QRQGFKFKLNTKVTG	acetylation	[1, 4, 7, 8]
273	QRQGFKFKLNTKVTG	succinylation	[7]
277	FKFKLNTKVTGATKK	acetylation	[1, 7]
277	FKFKLNTKVTGATKK	succinylation	[7]
277	FKFKLNTKVTGATKK	succinylation	[7]
288	ATKKSDGKIDVSVEA	acetylation	[4]
334	LGIELDPKGRIPVNN	acetylation	[4, 6, 7, 8]
334	LGIELDPKGRIPVNN	succinylation	[7]
334	LGIELDPKGRIPVNN	ubiquitination	[10]
346	VNNRFQTKIPNIYAI	acetylation	[1, 4, 6, 8]
410	GKSEEQLKEEGIEFK	acetylation	[1, 2, 3, 4, 5, 6, 7, 8, 11, 12, 13]
410	GKSEEQLKEEGIEFK	succinylation	[7]
420	GIEFKIGKFPFAANS	acetylation	[1, 2, 4, 5, 6, 7, 8, 12, 13]
420	GIEFKIGKFPFAANS	succinylation	[7]
430	FAANSRAKTNADTDG	acetylation	[7]
430	FAANSRAKTNADTDG	succinylation	[7]
445	MVKILGHKSTDRVLG	acetylation	[6, 7, 8]
445	MVKILGHKSTDRVLG	succinylation	[7]
505	NLAAAFGKPINF***	acetylation	[2, 3, 6, 7, 8]
505	NLAAAFGKPINF***	succinylation	[7]
505	NLAAAFGKPINF***	ubiquitination	[10]

Reference

 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405]
 [13] 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] 

Functional Description

 Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction. 

Sequence Annotation

 NP_BIND 71 80 FAD (By similarity).
 NP_BIND 183 185 FAD (By similarity).
 NP_BIND 220 227 NAD (By similarity).
 NP_BIND 361 364 FAD (By similarity).
 ACT_SITE 487 487 Proton acceptor (By similarity).
 BINDING 89 89 FAD (By similarity).
 BINDING 154 154 FAD; via amide nitrogen and carbonyl
 BINDING 243 243 NAD (By similarity).
 BINDING 278 278 NAD; via amide nitrogen and carbonyl
 BINDING 314 314 NAD; via amide nitrogen (By similarity).
 BINDING 355 355 FAD (By similarity).
 MOD_RES 127 127 N6-acetyllysine.
 MOD_RES 143 143 N6-acetyllysine (By similarity).
 MOD_RES 410 410 N6-acetyllysine (By similarity).
 MOD_RES 417 417 N6-acetyllysine (By similarity).
 DISULFID 80 85 Redox-active (By similarity).  

Keyword

 Acetylation; Complete proteome; Direct protein sequencing; Disulfide bond; FAD; Flavoprotein; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein; Redox-active center; Reference proteome; Transit peptide. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 509 AA 

Protein Sequence

Gene Ontology

 GO:0043159; C:acrosomal matrix; IDA:MGI.
 GO:0005929; C:cilium; IDA:MGI.
 GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IDA:MGI.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0004148; F:dihydrolipoyl dehydrogenase activity; IMP:MGI.
 GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
 GO:0045454; P:cell redox homeostasis; IEA:InterPro.
 GO:0007369; P:gastrulation; IMP:MGI.
 GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:MGI.
 GO:0006508; P:proteolysis; IDA:MGI.
 GO:0042391; P:regulation of membrane potential; IMP:MGI.
 GO:0048240; P:sperm capacitation; IDA:MGI. 

Interpro

 IPR016156; FAD/NAD-linked_Rdtase_dimer.
 IPR013027; FAD_pyr_nucl-diS_OxRdtase.
 IPR006258; Lipoamide_DH.
 IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
 IPR023753; Pyr_nucl-diS_OxRdtase_FAD/NAD.
 IPR012999; Pyr_OxRdtase_I_AS.
 IPR001327; Pyr_OxRdtase_NAD-bd_dom. 

Pfam

 PF00070; Pyr_redox
 PF07992; Pyr_redox_2
 PF02852; Pyr_redox_dim 

SMART

  

PROSITE

 PS00076; PYRIDINE_REDOX_1 

PRINTS

 PR00368; FADPNR.