UniProt Accession

 IDHP_MOUSE; P54071; Q8C2R9; Q9EQK1 

Genbank Protein ID

 U51167; AF212319; AK088110; AK145753; AK161640; AK169395; BC060030 

Genbank Nucleotide ID

 AAC52473.1; AAG43538.1; BAC40149.1; BAE26628.1; BAE36505.1; BAE41142.1; AAH60030.1 

Protein Name

 Isocitrate dehydrogenase [NADP], mitochondrial 

Protein Synonyms/Alias

 IDH; ICD-M; IDP; NADP(+)-specific ICDH; Oxalosuccinate decarboxylase 

Gene Name

 Idh2 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
45	HYAEKRIKVEKPVVE	acetylation	[1]
48	EKRIKVEKPVVEMDG	acetylation	[1]
48	EKRIKVEKPVVEMDG	ubiquitination	[2]
67	RIIWQFIKEKLILPH	acetylation	[1]
67	RIIWQFIKEKLILPH	ubiquitination	[2]
69	IWQFIKEKLILPHVD	acetylation	[1]
80	PHVDVQLKYFDLGLP	acetylation	[1]
106	DSALATQKYSVAVKC	acetylation	[1, 3]
106	DSALATQKYSVAVKC	ubiquitination	[2]
127	EARVEEFKLKKMWKS	acetylation	[1]
127	EARVEEFKLKKMWKS	ubiquitination	[2]
133	FKLKKMWKSPNGTIR	acetylation	[1]
155	FREPIICKNIPRLVP	acetylation	[1]
166	RLVPGWTKPITIGRH	acetylation	[1]
166	RLVPGWTKPITIGRH	ubiquitination	[2]
180	HAHGDQYKATDFVVD	acetylation	[1]
180	HAHGDQYKATDFVVD	ubiquitination	[2]
193	VDRAGTFKLVFTPKD	acetylation	[1]
199	FKLVFTPKDGSSAKE	acetylation	[1]
199	FKLVFTPKDGSSAKE	ubiquitination	[2]
243	FQYSIQKKWPLYLST	acetylation	[4]
251	WPLYLSTKNTILKAY	glycation	[5]
256	STKNTILKAYDGRFK	acetylation	[1, 4, 6, 7, 8, 9]
256	STKNTILKAYDGRFK	succinylation	[8]
256	STKNTILKAYDGRFK	ubiquitination	[2]
263	KAYDGRFKDIFQEIF	acetylation	[1, 4, 6, 7, 8, 9, 10, 11]
263	KAYDGRFKDIFQEIF	succinylation	[8]
263	KAYDGRFKDIFQEIF	ubiquitination	[2]
272	IFQEIFDKHYKTDFD	acetylation	[1, 3, 4, 6, 7, 8, 9, 10, 11]
272	IFQEIFDKHYKTDFD	succinylation	[8]
272	IFQEIFDKHYKTDFD	ubiquitination	[2]
275	EIFDKHYKTDFDKNK	acetylation	[1, 9, 11]
280	HYKTDFDKNKIWYEH	acetylation	[1, 4, 6, 8, 9]
280	HYKTDFDKNKIWYEH	succinylation	[8]
282	KTDFDKNKIWYEHRL	acetylation	[1, 4, 6, 8, 9]
282	KTDFDKNKIWYEHRL	succinylation	[8]
360	RHYREHQKGRPTSTN	acetylation	[4]
384	RGLEHRGKLDGNQDL	acetylation	[1, 4, 6, 7, 8, 9, 11, 12, 13]
384	RGLEHRGKLDGNQDL	succinylation	[8]
384	RGLEHRGKLDGNQDL	ubiquitination	[2]
400	RFAQTLEKVCVQTVE	acetylation	[1, 4, 6, 7, 9]
413	VESGAMTKDLAGCIH	acetylation	[1, 7, 8, 9]
413	VESGAMTKDLAGCIH	succinylation	[8]
426	IHGLSNVKLNEHFLN	acetylation	[4]
442	TDFLDTIKSNLDRAL	acetylation	[1, 4, 6, 8, 9, 11]

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] 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]
 [3] 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]
 [4] 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]
 [5] Glycation-induced inactivation of NADP(+)-dependent isocitrate dehydrogenase: implications for diabetes and aging.
 Kil IS, Lee JH, Shin AH, Park JW.
 Free Radic Biol Med. 2004 Dec 1;37(11):1765-78. [PMID: 15528036]
 [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] 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]
 [8] 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]
 [9] 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]
 [10] 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]
 [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 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

 Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex. 

Sequence Annotation

 NP_BIND 115 117 NADP (By similarity).
 NP_BIND 349 354 NADP (By similarity).
 REGION 134 140 Substrate binding (By similarity).
 METAL 291 291 Magnesium or manganese (By similarity).
 METAL 314 314 Magnesium or manganese (By similarity).
 BINDING 117 117 Substrate (By similarity).
 BINDING 122 122 NADP (By similarity).
 BINDING 149 149 Substrate (By similarity).
 BINDING 172 172 Substrate (By similarity).
 BINDING 299 299 NADP (By similarity).
 BINDING 367 367 NADP; via amide nitrogen and carbonyl
 MOD_RES 67 67 N6-acetyllysine (By similarity).
 MOD_RES 106 106 N6-acetyllysine.
 MOD_RES 155 155 N6-acetyllysine (By similarity).
 MOD_RES 166 166 N6-acetyllysine (By similarity).
 MOD_RES 180 180 N6-acetyllysine (By similarity).
 MOD_RES 256 256 N6-acetyllysine (By similarity).
 MOD_RES 263 263 N6-acetyllysine (By similarity).
 MOD_RES 272 272 N6-acetyllysine.
 MOD_RES 275 275 N6-acetyllysine (By similarity).
 MOD_RES 282 282 N6-acetyllysine (By similarity).
 MOD_RES 442 442 N6-acetyllysine (By similarity).  

Keyword

 Acetylation; Complete proteome; Direct protein sequencing; Glyoxylate bypass; Magnesium; Manganese; Metal-binding; Mitochondrion; NADP; Oxidoreductase; Reference proteome; Stress response; Transit peptide; Tricarboxylic acid cycle. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 452 AA 

Protein Sequence

Gene Ontology

 GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
 GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; ISS:UniProtKB.
 GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
 GO:0051287; F:NAD binding; IEA:InterPro.
 GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
 GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
 GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
 GO:0006950; P:response to stress; IEA:UniProtKB-KW.
 GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW. 

Interpro

 IPR019818; IsoCit/isopropylmalate_DH_CS.
 IPR004790; Isocitrate_DH_NADP.
 IPR024084; IsoPropMal-DH-like_dom. 

Pfam

 PF00180; Iso_dh 

SMART

  

PROSITE

 PS00470; IDH_IMDH 

PRINTS