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P48735

- IDHP_HUMAN

UniProt

P48735 - IDHP_HUMAN

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Protein

Isocitrate dehydrogenase [NADP], mitochondrial

Gene
IDH2
Organism
Homo sapiens (Human)
Status
Reviewed - 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

Binds 1 magnesium or manganese ion per subunit By similarity.

Sites

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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi115 – 1173NADP By similarity
Nucleotide bindingi349 – 3546NADP By 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. carbohydrate metabolic process Source: ProtInc
  3. cellular metabolic process Source: Reactome
  4. glyoxylate cycle Source: UniProtKB-KW
  5. isocitrate metabolic process Source: UniProtKB
  6. small molecule metabolic process Source: Reactome
  7. tricarboxylic acid cycle Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Glyoxylate bypass, Tricarboxylic acid cycle

Keywords - Ligandi

Magnesium, Manganese, Metal-binding, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS00021-MONOMER.
ReactomeiREACT_1785. 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:5383. IDH2.

Subcellular locationi

GO - Cellular componenti

  1. mitochondrial inner membrane Source: Ensembl
  2. mitochondrial matrix Source: Reactome
  3. mitochondrion Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

D-2-hydroxyglutaric aciduria 2 (D2HGA2) [MIM:613657]: A neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti140 – 1401R → G in D2HGA2. 1 Publication
VAR_065174
Natural varianti140 – 1401R → Q in D2HGA2. 1 Publication
VAR_065175

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi413 – 4131K → A: 44-fold loss in activity. 1 Publication
Mutagenesisi413 – 4131K → Q: 20-fold decrease in Vmax. 1 Publication
Mutagenesisi413 – 4131K → R: No appreciable difference in Km for isocitrate and NADP. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi613657. phenotype.
Orphaneti79315. D-2-hydroxyglutaric aciduria.
296. Enchondromatosis.
163634. Maffucci syndrome.
PharmGKBiPA29631.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3939Mitochondrion By similarityAdd
BLAST
Chaini40 – 452413Isocitrate dehydrogenase [NADP], mitochondrialPRO_0000014420Add
BLAST

Amino acid modifications

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

Post-translational modificationi

Acetylation at Lys-413 dramatically reduces catalytic activity. Deacetylated by SIRT3.1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP48735.
PaxDbiP48735.
PeptideAtlasiP48735.
PRIDEiP48735.

2D gel databases

OGPiP48735.
UCD-2DPAGEP48735.

PTM databases

PhosphoSiteiP48735.

Expressioni

Gene expression databases

ArrayExpressiP48735.
BgeeiP48735.
CleanExiHS_IDH2.
GenevestigatoriP48735.

Organism-specific databases

HPAiHPA007831.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi109644. 8 interactions.
IntActiP48735. 2 interactions.
MINTiMINT-3016964.
STRINGi9606.ENSP00000331897.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi50 – 545
Helixi57 – 6913
Turni70 – 745
Beta strandi79 – 835
Helixi86 – 916
Turni92 – 943
Helixi95 – 10713
Beta strandi108 – 1125
Helixi120 – 1267
Helixi135 – 1439
Beta strandi146 – 1516
Beta strandi168 – 1725
Helixi177 – 1804
Beta strandi182 – 1865
Beta strandi190 – 1989
Beta strandi205 – 21410
Beta strandi216 – 2249
Helixi225 – 24218
Beta strandi246 – 2505
Turni252 – 2543
Helixi258 – 27316
Helixi275 – 2806
Beta strandi285 – 2895
Helixi290 – 29910
Beta strandi304 – 3085
Helixi310 – 32314
Helixi327 – 3293
Beta strandi330 – 3356
Beta strandi342 – 3487
Helixi352 – 3598
Helixi369 – 38618
Helixi389 – 40719
Helixi413 – 4208
Helixi422 – 4243
Turni427 – 4293
Helixi434 – 45219

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4JA8X-ray1.55A/B41-452[»]
ProteinModelPortaliP48735.
SMRiP48735. Positions 41-452.

Family & Domainsi

Region

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

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0538.
HOGENOMiHOG000019858.
HOVERGENiHBG006119.
InParanoidiP48735.
KOiK00031.
OMAiCFQYAIG.
OrthoDBiEOG7QNVKS.
PhylomeDBiP48735.
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.

P48735-1 [UniParc]FASTAAdd to Basket

« Hide

MAGYLRVVRS LCRASGSRPA WAPAALTAPT SQEQPRRHYA DKRIKVAKPV    50
VEMDGDEMTR IIWQFIKEKL ILPHVDIQLK YFDLGLPNRD QTDDQVTIDS 100
ALATQKYSVA VKCATITPDE ARVEEFKLKK MWKSPNGTIR NILGGTVFRE 150
PIICKNIPRL VPGWTKPITI GRHAHGDQYK ATDFVADRAG TFKMVFTPKD 200
GSGVKEWEVY NFPAGGVGMG MYNTDESISG FAHSCFQYAI QKKWPLYMST 250
KNTILKAYDG RFKDIFQEIF DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS 300
SGGFVWACKN YDGDVQSDIL AQGFGSLGLM TSVLVCPDGK TIEAEAAHGT 350
VTRHYREHQK GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD LIRFAQMLEK 400
VCVETVESGA MTKDLAGCIH GLSNVKLNEH FLNTTDFLDT IKSNLDRALG 450
RQ 452
Length:452
Mass (Da):50,909
Last modified:April 3, 2002 - v2
Checksum:i4DDC830AFC06AB52
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti140 – 1401R → G in D2HGA2. 1 Publication
VAR_065174
Natural varianti140 – 1401R → Q in D2HGA2. 1 Publication
VAR_065175

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti34 – 341Q → H in CAA49208. 1 Publication
Sequence conflicti435 – 4351T → M in CAA49208. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X69433 mRNA. Translation: CAA49208.1.
AK312627 mRNA. Translation: BAG35513.1.
CH471101 Genomic DNA. Translation: EAX02082.1.
BC009244 mRNA. Translation: AAH09244.1.
BC071828 mRNA. Translation: AAH71828.1.
CCDSiCCDS10359.1.
PIRiS57499.
RefSeqiNP_001276839.1. NM_001289910.1.
NP_001277043.1. NM_001290114.1.
NP_002159.2. NM_002168.3.
UniGeneiHs.596461.

Genome annotation databases

EnsembliENST00000330062; ENSP00000331897; ENSG00000182054.
GeneIDi3418.
KEGGihsa:3418.
UCSCiuc002box.3. human.

Polymorphism databases

DMDMi20141568.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X69433 mRNA. Translation: CAA49208.1 .
AK312627 mRNA. Translation: BAG35513.1 .
CH471101 Genomic DNA. Translation: EAX02082.1 .
BC009244 mRNA. Translation: AAH09244.1 .
BC071828 mRNA. Translation: AAH71828.1 .
CCDSi CCDS10359.1.
PIRi S57499.
RefSeqi NP_001276839.1. NM_001289910.1.
NP_001277043.1. NM_001290114.1.
NP_002159.2. NM_002168.3.
UniGenei Hs.596461.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4JA8 X-ray 1.55 A/B 41-452 [» ]
ProteinModelPortali P48735.
SMRi P48735. Positions 41-452.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109644. 8 interactions.
IntActi P48735. 2 interactions.
MINTi MINT-3016964.
STRINGi 9606.ENSP00000331897.

PTM databases

PhosphoSitei P48735.

Polymorphism databases

DMDMi 20141568.

2D gel databases

OGPi P48735.
UCD-2DPAGE P48735.

Proteomic databases

MaxQBi P48735.
PaxDbi P48735.
PeptideAtlasi P48735.
PRIDEi P48735.

Protocols and materials databases

DNASUi 3418.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000330062 ; ENSP00000331897 ; ENSG00000182054 .
GeneIDi 3418.
KEGGi hsa:3418.
UCSCi uc002box.3. human.

Organism-specific databases

CTDi 3418.
GeneCardsi GC15M090626.
HGNCi HGNC:5383. IDH2.
HPAi HPA007831.
MIMi 147650. gene.
613657. phenotype.
neXtProti NX_P48735.
Orphaneti 79315. D-2-hydroxyglutaric aciduria.
296. Enchondromatosis.
163634. Maffucci syndrome.
PharmGKBi PA29631.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0538.
HOGENOMi HOG000019858.
HOVERGENi HBG006119.
InParanoidi P48735.
KOi K00031.
OMAi CFQYAIG.
OrthoDBi EOG7QNVKS.
PhylomeDBi P48735.
TreeFami TF300428.

Enzyme and pathway databases

BioCyci MetaCyc:HS00021-MONOMER.
Reactomei REACT_1785. Citric acid cycle (TCA cycle).

Miscellaneous databases

ChiTaRSi IDH2. human.
GeneWikii IDH2.
GenomeRNAii 3418.
NextBioi 13474.
PROi P48735.
SOURCEi Search...

Gene expression databases

ArrayExpressi P48735.
Bgeei P48735.
CleanExi HS_IDH2.
Genevestigatori P48735.

Family and domain databases

Gene3Di 3.40.718.10. 1 hit.
InterProi IPR019818. IsoCit/isopropylmalate_DH_CS.
IPR004790. Isocitrate_DH_NADP.
IPR024084. IsoPropMal-DH-like_dom.
[Graphical view ]
PANTHERi PTHR11822. PTHR11822. 1 hit.
Pfami PF00180. Iso_dh. 1 hit.
[Graphical view ]
PIRSFi PIRSF000108. IDH_NADP. 1 hit.
TIGRFAMsi TIGR00127. nadp_idh_euk. 1 hit.
PROSITEi PS00470. IDH_IMDH. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Huh T.-L., Oh I.-U., Kim Y.O., Huh J.-W., Song B.J.
    Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Heart.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Heart.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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].
    Tissue: Colon and Skin.
  5. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-67; LYS-106; LYS-155; LYS-166; LYS-180; LYS-256; LYS-263; LYS-272; LYS-275; LYS-282 AND LYS-442, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status."
    Yu W., Dittenhafer-Reed K.E., Denu J.M.
    J. Biol. Chem. 287:14078-14086(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-413, MUTAGENESIS OF LYS-413.
  8. Cited for: VARIANTS D2HGA2 GLN-140 AND GLY-140.

Entry informationi

Entry nameiIDHP_HUMAN
AccessioniPrimary (citable) accession number: P48735
Secondary accession number(s): B2R6L6, Q96GT3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: April 3, 2002
Last modified: September 3, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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