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Protein

Isocitrate dehydrogenase [NADP], mitochondrial

Gene

Idh2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

Isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH.

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 1 Mg(2+) or Mn2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei117 – 1171SubstrateBy similarity
Binding sitei122 – 1221NADPBy similarity
Binding sitei149 – 1491SubstrateBy similarity
Binding sitei172 – 1721SubstrateBy similarity
Sitei179 – 1791Critical for catalysisBy similarity
Sitei251 – 2511Critical for catalysisBy similarity
Metal bindingi291 – 2911Magnesium or manganeseBy similarity
Binding sitei299 – 2991NADPBy similarity
Metal bindingi314 – 3141Magnesium or manganeseBy similarity
Binding sitei367 – 3671NADP; via amide nitrogen and carbonyl oxygenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi115 – 1173NADPBy similarity
Nucleotide bindingi349 – 3546NADPBy similarity

GO - Molecular functioni

  1. isocitrate dehydrogenase (NADP+) activity Source: UniProtKB
  2. magnesium ion binding Source: UniProtKB
  3. NAD binding Source: InterPro

GO - Biological processi

  1. 2-oxoglutarate metabolic process Source: UniProtKB
  2. glyoxylate cycle Source: UniProtKB-KW
  3. isocitrate metabolic process Source: UniProtKB
  4. tricarboxylic acid cycle Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Glyoxylate bypass, Stress response, Tricarboxylic acid cycle

Keywords - Ligandi

Magnesium, Manganese, Metal-binding, NADP

Enzyme and pathway databases

ReactomeiREACT_249033. Citric acid cycle (TCA cycle).

Names & Taxonomyi

Protein namesi
Recommended name:
Isocitrate dehydrogenase [NADP], mitochondrial (EC:1.1.1.42)
Short name:
IDH
Alternative name(s):
ICD-M
IDP
NADP(+)-specific ICDH
Oxalosuccinate decarboxylase
Gene namesi
Name:Idh2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:96414. Idh2.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: MGI
  2. mitochondrial inner membrane Source: MGI
  3. mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3939MitochondrionBy similarityAdd
BLAST
Chaini40 – 452413Isocitrate dehydrogenase [NADP], mitochondrialPRO_0000014421Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei45 – 451N6-acetyllysine1 Publication
Modified residuei48 – 481N6-acetyllysine1 Publication
Modified residuei67 – 671N6-acetyllysineBy similarity
Modified residuei69 – 691N6-acetyllysine1 Publication
Modified residuei80 – 801N6-acetyllysine; alternate1 Publication
Modified residuei80 – 801N6-succinyllysine; alternate1 Publication
Modified residuei106 – 1061N6-acetyllysine; alternate1 Publication
Modified residuei106 – 1061N6-succinyllysine; alternate1 Publication
Modified residuei155 – 1551N6-acetyllysine1 Publication
Modified residuei166 – 1661N6-acetyllysine; alternate1 Publication
Modified residuei166 – 1661N6-succinyllysine; alternate1 Publication
Modified residuei180 – 1801N6-acetyllysine; alternate1 Publication
Modified residuei180 – 1801N6-succinyllysine; alternate1 Publication
Modified residuei193 – 1931N6-acetyllysine; alternate1 Publication
Modified residuei193 – 1931N6-succinyllysine; alternate1 Publication
Modified residuei199 – 1991N6-acetyllysine1 Publication
Modified residuei256 – 2561N6-acetyllysine; alternate1 Publication
Modified residuei256 – 2561N6-succinyllysine; alternate1 Publication
Modified residuei263 – 2631N6-acetyllysine2 Publications
Modified residuei272 – 2721N6-acetyllysine1 Publication
Modified residuei275 – 2751N6-acetyllysineBy similarity
Modified residuei280 – 2801N6-acetyllysine1 Publication
Modified residuei282 – 2821N6-acetyllysine; alternate1 Publication
Modified residuei282 – 2821N6-succinyllysine; alternate1 Publication
Modified residuei384 – 3841N6-acetyllysine; alternate1 Publication
Modified residuei384 – 3841N6-succinyllysine; alternate1 Publication
Modified residuei400 – 4001N6-acetyllysine1 Publication
Modified residuei413 – 4131N6-acetyllysineBy similarity
Modified residuei442 – 4421N6-acetyllysine1 Publication

Post-translational modificationi

Acetylation at Lys-413 dramatically reduces catalytic activity. Deacetylated by SIRT3 (By similarity).By similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP54071.
PaxDbiP54071.
PRIDEiP54071.

PTM databases

PhosphoSiteiP54071.

Expressioni

Tissue specificityi

Heart > kidney >> other tissues.1 Publication

Inductioni

By oxidative stress (at protein level).1 Publication

Gene expression databases

BgeeiP54071.
CleanExiMM_IDH2.
ExpressionAtlasiP54071. baseline and differential.
GenevestigatoriP54071.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi234733. 2 interactions.
IntActiP54071. 4 interactions.
MINTiMINT-4114220.

Structurei

3D structure databases

ProteinModelPortaliP54071.
SMRiP54071. Positions 40-452.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni134 – 1407Substrate bindingBy similarity

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0538.
GeneTreeiENSGT00390000012547.
HOGENOMiHOG000019858.
HOVERGENiHBG006119.
InParanoidiP54071.
KOiK00031.
OMAiQVIEHDV.
OrthoDBiEOG7QNVKS.
PhylomeDBiP54071.
TreeFamiTF300428.

Family and domain databases

Gene3Di3.40.718.10. 1 hit.
InterProiIPR019818. IsoCit/isopropylmalate_DH_CS.
IPR004790. Isocitrate_DH_NADP.
IPR024084. IsoPropMal-DH-like_dom.
[Graphical view]
PANTHERiPTHR11822. PTHR11822. 1 hit.
PfamiPF00180. Iso_dh. 1 hit.
[Graphical view]
PIRSFiPIRSF000108. IDH_NADP. 1 hit.
TIGRFAMsiTIGR00127. nadp_idh_euk. 1 hit.
PROSITEiPS00470. IDH_IMDH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P54071-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAGYLRAVSS LCRASGSART WAPAALTVPS WPEQPRRHYA EKRIKVEKPV
60 70 80 90 100
VEMDGDEMTR IIWQFIKEKL ILPHVDVQLK YFDLGLPNRD QTNDQVTIDS
110 120 130 140 150
ALATQKYSVA VKCATITPDE ARVEEFKLKK MWKSPNGTIR NILGGTVFRE
160 170 180 190 200
PIICKNIPRL VPGWTKPITI GRHAHGDQYK ATDFVVDRAG TFKLVFTPKD
210 220 230 240 250
GSSAKEWEVY NFPAGGVGMG MYNTDESISG FAHSCFQYSI QKKWPLYLST
260 270 280 290 300
KNTILKAYDG RFKDIFQEIF DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS
310 320 330 340 350
SGGFVWACKN YDGDVQSDIL AQGFGSLGLM TSVLVCPDGK TIEAEAAHGT
360 370 380 390 400
VTRHYREHQK GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD LIRFAQTLEK
410 420 430 440 450
VCVQTVESGA MTKDLAGCIH GLSNVKLNEH FLNTTDFLDT IKSNLDRALG

KQ
Length:452
Mass (Da):50,906
Last modified:September 11, 2007 - v3
Checksum:i19BB5CF78512ECAB
GO

Sequence cautioni

The sequence AAC52473.1 differs from that shown. Reason: Frameshift at positions 5 and 11. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti104 – 1041T → A in AAC52473. (PubMed:8867815)Curated
Sequence conflicti109 – 1091V → M in AAC52473. (PubMed:8867815)Curated
Sequence conflicti152 – 1521I → S in AAC52473. (PubMed:8867815)Curated
Sequence conflicti200 – 2001D → N in AAC52473. (PubMed:8867815)Curated
Sequence conflicti214 – 2141A → G in AAC52473. (PubMed:8867815)Curated
Sequence conflicti280 – 2801K → R in AAC52473. (PubMed:8867815)Curated
Sequence conflicti280 – 2801K → R in AAG43538. (PubMed:11278619)Curated
Sequence conflicti322 – 3232QG → SR in AAC52473. (PubMed:8867815)Curated
Sequence conflicti367 – 3682NP → KG in AAC52473. (PubMed:8867815)Curated
Sequence conflicti398 – 3981L → R in AAC52473. (PubMed:8867815)Curated
Sequence conflicti408 – 4081Missing in AAC52473. (PubMed:8867815)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U51167 mRNA. Translation: AAC52473.1. Frameshift.
AF212319 mRNA. Translation: AAG43538.1.
AK088110 mRNA. Translation: BAC40149.1.
AK145753 mRNA. Translation: BAE26628.1.
AK161640 mRNA. Translation: BAE36505.1.
AK169395 mRNA. Translation: BAE41142.1.
BC060030 mRNA. Translation: AAH60030.1.
CCDSiCCDS39994.1.
RefSeqiNP_766599.2. NM_173011.2.
UniGeneiMm.246432.
Mm.290925.

Genome annotation databases

EnsembliENSMUST00000107384; ENSMUSP00000103007; ENSMUSG00000030541.
GeneIDi269951.
KEGGimmu:269951.
UCSCiuc009hzm.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U51167 mRNA. Translation: AAC52473.1. Frameshift.
AF212319 mRNA. Translation: AAG43538.1.
AK088110 mRNA. Translation: BAC40149.1.
AK145753 mRNA. Translation: BAE26628.1.
AK161640 mRNA. Translation: BAE36505.1.
AK169395 mRNA. Translation: BAE41142.1.
BC060030 mRNA. Translation: AAH60030.1.
CCDSiCCDS39994.1.
RefSeqiNP_766599.2. NM_173011.2.
UniGeneiMm.246432.
Mm.290925.

3D structure databases

ProteinModelPortaliP54071.
SMRiP54071. Positions 40-452.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi234733. 2 interactions.
IntActiP54071. 4 interactions.
MINTiMINT-4114220.

Chemistry

ChEMBLiCHEMBL2176829.

PTM databases

PhosphoSiteiP54071.

Proteomic databases

MaxQBiP54071.
PaxDbiP54071.
PRIDEiP54071.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000107384; ENSMUSP00000103007; ENSMUSG00000030541.
GeneIDi269951.
KEGGimmu:269951.
UCSCiuc009hzm.2. mouse.

Organism-specific databases

CTDi3418.
MGIiMGI:96414. Idh2.

Phylogenomic databases

eggNOGiCOG0538.
GeneTreeiENSGT00390000012547.
HOGENOMiHOG000019858.
HOVERGENiHBG006119.
InParanoidiP54071.
KOiK00031.
OMAiQVIEHDV.
OrthoDBiEOG7QNVKS.
PhylomeDBiP54071.
TreeFamiTF300428.

Enzyme and pathway databases

ReactomeiREACT_249033. Citric acid cycle (TCA cycle).

Miscellaneous databases

ChiTaRSiIdh2. mouse.
NextBioi393111.
PROiP54071.
SOURCEiSearch...

Gene expression databases

BgeeiP54071.
CleanExiMM_IDH2.
ExpressionAtlasiP54071. baseline and differential.
GenevestigatoriP54071.

Family and domain databases

Gene3Di3.40.718.10. 1 hit.
InterProiIPR019818. IsoCit/isopropylmalate_DH_CS.
IPR004790. Isocitrate_DH_NADP.
IPR024084. IsoPropMal-DH-like_dom.
[Graphical view]
PANTHERiPTHR11822. PTHR11822. 1 hit.
PfamiPF00180. Iso_dh. 1 hit.
[Graphical view]
PIRSFiPIRSF000108. IDH_NADP. 1 hit.
TIGRFAMsiTIGR00127. nadp_idh_euk. 1 hit.
PROSITEiPS00470. IDH_IMDH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of the cDNA of mouse mitochondrial NADP-dependent isocitrate dehydrogenase and the expression of the gene during lymphocyte activation."
    Yang L., Luo H., Vinay P., Wu J.
    J. Cell. Biochem. 60:400-410(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
    Tissue: Heart.
  2. "Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase."
    Jo S.-H., Son M.-K., Koh H.-J., Lee S.-M., Song I.-H., Kim Y.-O., Lee Y.-S., Jeong K.-S., Kim W.B., Park J.-W., Song B.J., Huhe T.-L.
    J. Biol. Chem. 276:16168-16176(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and NOD.
    Tissue: Embryo, Heart and Thymus.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N-3.
    Tissue: Mammary tumor.
  5. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 44-60 AND 81-89, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6.
    Tissue: Brain.
  6. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-263, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-80; LYS-106; LYS-166; LYS-180; LYS-193; LYS-256; LYS-282 AND LYS-384, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast and Liver.
  7. "Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
    Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
    Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-45; LYS-48; LYS-69; LYS-80; LYS-106; LYS-155; LYS-166; LYS-180; LYS-193; LYS-199; LYS-256; LYS-263; LYS-272; LYS-280; LYS-282; LYS-384; LYS-400 AND LYS-442, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiIDHP_MOUSE
AccessioniPrimary (citable) accession number: P54071
Secondary accession number(s): Q8C2R9, Q9EQK1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 11, 2007
Last modified: February 4, 2015
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.