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P48735 (IDHP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Isocitrate dehydrogenase [NADP], mitochondrial

Short name=IDH
EC=1.1.1.42
Alternative name(s):
ICD-M
IDP
NADP(+)-specific ICDH
Oxalosuccinate decarboxylase
Gene names
Name:IDH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length452 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

Binds 1 magnesium or manganese ion per subunit By similarity.

Subunit structure

Homodimer.

Subcellular location

Mitochondrion.

Post-translational modification

Acetylation at Lys-413 dramatically reduces catalytic activity. Deacetylated by SIRT3. Ref.7

Involvement in disease

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. Ref.8

Sequence similarities

Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3939Mitochondrion By similarity
Chain40 – 452413Isocitrate dehydrogenase [NADP], mitochondrial
PRO_0000014420

Regions

Nucleotide binding115 – 1173NADP By similarity
Nucleotide binding349 – 3546NADP By similarity
Region134 – 1407Substrate binding By similarity

Sites

Metal binding2911Magnesium or manganese By similarity
Metal binding3141Magnesium or manganese By similarity
Binding site1171Substrate By similarity
Binding site1221NADP By similarity
Binding site1491Substrate By similarity
Binding site1721Substrate By similarity
Binding site2991NADP By similarity
Binding site3671NADP; via amide nitrogen and carbonyl oxygen By similarity
Site1791Critical for catalysis By similarity
Site2511Critical for catalysis By similarity

Amino acid modifications

Modified residue451N6-acetyllysine By similarity
Modified residue481N6-acetyllysine By similarity
Modified residue671N6-acetyllysine Ref.5
Modified residue691N6-acetyllysine By similarity
Modified residue801N6-acetyllysine; alternate By similarity
Modified residue801N6-succinyllysine; alternate By similarity
Modified residue1061N6-acetyllysine; alternate Ref.5
Modified residue1061N6-succinyllysine; alternate By similarity
Modified residue1551N6-acetyllysine Ref.5
Modified residue1661N6-acetyllysine; alternate Ref.5
Modified residue1661N6-succinyllysine; alternate By similarity
Modified residue1801N6-acetyllysine; alternate Ref.5
Modified residue1801N6-succinyllysine; alternate By similarity
Modified residue1931N6-acetyllysine; alternate By similarity
Modified residue1931N6-succinyllysine; alternate By similarity
Modified residue1991N6-acetyllysine By similarity
Modified residue2561N6-acetyllysine; alternate Ref.5
Modified residue2561N6-succinyllysine; alternate By similarity
Modified residue2631N6-acetyllysine Ref.5
Modified residue2721N6-acetyllysine Ref.5
Modified residue2751N6-acetyllysine Ref.5
Modified residue2801N6-acetyllysine By similarity
Modified residue2821N6-acetyllysine; alternate Ref.5
Modified residue2821N6-succinyllysine; alternate By similarity
Modified residue3841N6-acetyllysine; alternate By similarity
Modified residue3841N6-succinyllysine; alternate By similarity
Modified residue4001N6-acetyllysine By similarity
Modified residue4131N6-acetyllysine Ref.7
Modified residue4421N6-acetyllysine Ref.5

Natural variations

Natural variant1401R → G in D2HGA2. Ref.8
VAR_065174
Natural variant1401R → Q in D2HGA2. Ref.8
VAR_065175

Experimental info

Mutagenesis4131K → A: 44-fold loss in activity. Ref.7
Mutagenesis4131K → Q: 20-fold decrease in Vmax. Ref.7
Mutagenesis4131K → R: No appreciable difference in Km for isocitrate and NADP. Ref.7
Sequence conflict341Q → H in CAA49208. Ref.1
Sequence conflict4351T → M in CAA49208. Ref.1

Secondary structure

................................................................. 452
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P48735 [UniParc].

Last modified April 3, 2002. Version 2.
Checksum: 4DDC830AFC06AB52

FASTA45250,909
        10         20         30         40         50         60 
MAGYLRVVRS LCRASGSRPA WAPAALTAPT SQEQPRRHYA DKRIKVAKPV VEMDGDEMTR 

        70         80         90        100        110        120 
IIWQFIKEKL ILPHVDIQLK YFDLGLPNRD QTDDQVTIDS ALATQKYSVA VKCATITPDE 

       130        140        150        160        170        180 
ARVEEFKLKK MWKSPNGTIR NILGGTVFRE PIICKNIPRL VPGWTKPITI GRHAHGDQYK 

       190        200        210        220        230        240 
ATDFVADRAG TFKMVFTPKD GSGVKEWEVY NFPAGGVGMG MYNTDESISG FAHSCFQYAI 

       250        260        270        280        290        300 
QKKWPLYMST KNTILKAYDG RFKDIFQEIF DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS 

       310        320        330        340        350        360 
SGGFVWACKN YDGDVQSDIL AQGFGSLGLM TSVLVCPDGK TIEAEAAHGT VTRHYREHQK 

       370        380        390        400        410        420 
GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD LIRFAQMLEK VCVETVESGA MTKDLAGCIH 

       430        440        450 
GLSNVKLNEH FLNTTDFLDT IKSNLDRALG RQ 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"IDH2 mutations in patients with D-2-hydroxyglutaric aciduria."
Kranendijk M., Struys E.A., van Schaftingen E., Gibson K.M., Kanhai W.A., van der Knaap M.S., Amiel J., Buist N.R., Das A.M., de Klerk J.B., Feigenbaum A.S., Grange D.K., Hofstede F.C., Holme E., Kirk E.P., Korman S.H., Morava E., Morris A. expand/collapse author list , Smeitink J., Sukhai R.N., Vallance H., Jakobs C., Salomons G.S.
Science 330:336-336(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS D2HGA2 GLN-140 AND GLY-140.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10359.1.
PIRS57499.
RefSeqNP_001276839.1. NM_001289910.1.
NP_001277043.1. NM_001290114.1.
NP_002159.2. NM_002168.3.
UniGeneHs.596461.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4JA8X-ray1.55A/B41-452[»]
ProteinModelPortalP48735.
SMRP48735. Positions 41-452.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109644. 5 interactions.
IntActP48735. 2 interactions.
MINTMINT-3016964.
STRING9606.ENSP00000331897.

PTM databases

PhosphoSiteP48735.

Polymorphism databases

DMDM20141568.

2D gel databases

OGPP48735.
UCD-2DPAGEP48735.

Proteomic databases

MaxQBP48735.
PaxDbP48735.
PeptideAtlasP48735.
PRIDEP48735.

Protocols and materials databases

DNASU3418.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330062; ENSP00000331897; ENSG00000182054.
GeneID3418.
KEGGhsa:3418.
UCSCuc002box.3. human.

Organism-specific databases

CTD3418.
GeneCardsGC15M090626.
HGNCHGNC:5383. IDH2.
HPAHPA007831.
MIM147650. gene.
613657. phenotype.
neXtProtNX_P48735.
Orphanet79315. D-2-hydroxyglutaric aciduria.
296. Enchondromatosis.
163634. Maffucci syndrome.
PharmGKBPA29631.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0538.
HOGENOMHOG000019858.
HOVERGENHBG006119.
InParanoidP48735.
KOK00031.
OMACFQYAIG.
OrthoDBEOG7QNVKS.
PhylomeDBP48735.
TreeFamTF300428.

Enzyme and pathway databases

BioCycMetaCyc:HS00021-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP48735.
BgeeP48735.
CleanExHS_IDH2.
GenevestigatorP48735.

Family and domain databases

Gene3D3.40.718.10. 1 hit.
InterProIPR019818. IsoCit/isopropylmalate_DH_CS.
IPR004790. Isocitrate_DH_NADP.
IPR024084. IsoPropMal-DH-like_dom.
[Graphical view]
PANTHERPTHR11822. PTHR11822. 1 hit.
PfamPF00180. Iso_dh. 1 hit.
[Graphical view]
PIRSFPIRSF000108. IDH_NADP. 1 hit.
TIGRFAMsTIGR00127. nadp_idh_euk. 1 hit.
PROSITEPS00470. IDH_IMDH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIDH2. human.
GeneWikiIDH2.
GenomeRNAi3418.
NextBio13474.
PROP48735.
SOURCESearch...

Entry information

Entry nameIDHP_HUMAN
AccessionPrimary (citable) accession number: P48735
Secondary accession number(s): B2R6L6, Q96GT3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: April 3, 2002
Last modified: July 9, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM