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Reviewed, UniProtKB/Swiss-Prot O75874 (IDHC_HUMAN)

Last modified July 7, 2009. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Isocitrate dehydrogenase [NADP] cytoplasmic
      Short name=IDH
    EC=1.1.1.42
Alternative name(s):
    Cytosolic NADP-isocitrate dehydrogenase
    Oxalosuccinate decarboxylase
    NADP(+)-specific ICDH
    IDP
Gene names
Name: IDH1
Synonyms: PICD
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length414 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

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

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

Cofactor

Binds 1 magnesium or manganese ion per subunit.

Subunit structure

Homodimer. Ref.8

Subcellular location

Cytoplasm. Peroxisome. Ref.2

Involvement in disease

Defects in IDH1 are a cause of glioblastoma multiforme (GBM) [MIM:137800]; also called familial glioma of brain. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas.

Miscellaneous

Cancer mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas.

Sequence similarities

Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 414414Isocitrate dehydrogenase [NADP] cytoplasmic
PRO_0000083575

Regions

Nucleotide binding75 – 773NADP
Nucleotide binding310 – 3156NADP
Region94 – 1007Substrate binding

Sites

Metal binding2521Magnesium or manganese
Metal binding2751Magnesium or manganese
Binding site771Substrate
Binding site821NADP
Binding site1091Substrate
Binding site1321Substrate
Binding site2601NADP
Binding site3281NADP; via amide nitrogen and carbonyl oxygen
Site1391Critical for catalysis
Site2121Critical for catalysis

Natural variations

Natural variant1321R → C in a colorectal cancer sample and GBM; somatic mutation.
VAR_036013
Natural variant1321R → G in GBM; somatic mutation.
VAR_055454
Natural variant1321R → H in GBM; somatic mutation.
VAR_055455
Natural variant1321R → L in GBM; somatic mutation.
VAR_055456
Natural variant1321R → S in GBM; somatic mutation.
VAR_055457
Natural variant1781V → I: dbSNP rs34218846.
VAR_049780

Experimental info

Sequence conflict321F → I in CAB66637. Ref.3
Sequence conflict1261K → E in CAB66637. Ref.3
Sequence conflict2181K → I in AAD02918. Ref.1
Sequence conflict3291P → L in AAD02918. Ref.1
Sequence conflict3811K → R in AAD02918. Ref.1

Secondary structure

................................................................ 414
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O75874-1 [UniParc].

Last modified July 11, 2002. Version 2.
Checksum: 60428B0B6E5851DC

FASTA41446,659
        10         20         30         40         50         60 
MSKKISGGSV VEMQGDEMTR IIWELIKEKL IFPYVELDLH SYDLGIENRD ATNDQVTKDA 

        70         80         90        100        110        120 
AEAIKKHNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL 

       130        140        150        160        170        180 
VSGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITYTPSD GTQKVTYLVH NFEEGGGVAM 

       190        200        210        220        230        240 
GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSQFE 

       250        260        270        280        290        300 
AQKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLVCPDG 

       310        320        330        340        350        360 
KTVEAEAAHG TVTRHYRMYQ KGQETSTNPI ASIFAWTRGL AHRAKLDNNK ELAFFANALE 

       370        380        390        400        410 
EVSIETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKIKLA QAKL 

« Hide

References

« Hide 'large scale' references
[1]"Cytosolic isocitrate dehydrogenase in humans, mice, and voles and phylogenetic analysis of the enzyme family."
Nekrutenko A., Hillis D.M., Patton J.C., Bradley R.D., Baker R.J.
Mol. Biol. Evol. 15:1674-1684(1998) [PubMed: 9866202] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The human PICD gene encodes a cytoplasmic and peroxisomal NADP(+)-dependent isocitrate dehydrogenase."
Geisbrecht B.V., Gould S.J.
J. Biol. Chem. 274:30527-30533(1999) [PubMed: 10521434] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
[3]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[5]Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 5-20; 30-49; 101-109; 120-132; 141-212; 223-233; 250-270; 322-338 AND 389-400, MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[6]"Differential gene expression in epithelial cells induced by bile salts: identification by RNA arbitrarily primed PCR."
Kullmann F., Vogt T., Welsh J., McClelland M.
Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 100-253.
[7]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]"Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity."
Xu X., Zhao J., Xu Z., Peng B., Huang Q., Arnold E., Ding J.
J. Biol. Chem. 279:33946-33957(2004) [PubMed: 15173171] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEXES WITH NADP; ISOCITRATE AND CALCIUM IONS, SUBUNIT.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed: 16959974] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-132.
[10]"An integrated genomic analysis of human glioblastoma multiforme."
Parsons D.W., Jones S., Zhang X., Lin J.C.-H., Leary R.J., Angenendt P., Mankoo P., Carter H., Siu I.-M., Gallia G.L., Olivi A., McLendon R., Rasheed B.A., Keir S., Nikolskaya T., Nikolsky Y., Busam D.A., Tekleab H. expand/collapse author list , Diaz L.A. Jr., Hartigan J., Smith D.R., Strausberg R.L., Marie S.K.N., Shinjo S.M.O., Yan H., Riggins G.J., Bigner D.D., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W.
Science 321:1807-1812(2008) [PubMed: 18772396] [Abstract]
Cited for: VARIANTS GBM HIS-132 AND SER-132.
[11]"IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors."
Bleeker F.E., Lamba S., Leenstra S., Troost D., Hulsebos T., Vandertop W.P., Frattini M., Molinari F., Knowles M., Cerrato A., Rodolfo M., Scarpa A., Felicioni L., Buttitta F., Malatesta S., Marchetti A., Bardelli A.
Hum. Mutat. 30:7-11(2009) [PubMed: 19117336] [Abstract]
Cited for: VARIANTS GBM CYS-132; GLY-132 AND LEU-132, POSSIBLE ROLE IN GLIOMAS.
+Additional computationally mapped references.

Web resources

Wikipedia

Isocitrate dehydrogenase entry

Cross-references

Sequence databases

AF020038 mRNA. Translation: AAD02918.1.
AF113917 mRNA. Translation: AAD29284.1.
AL136702 mRNA. Translation: CAB66637.1.
BC012846 mRNA. Translation: AAH12846.1.
U62389 mRNA. Translation: AAB17375.1.
IPIIPI00027223.
PIRT46280.
RefSeqNP_005887.2.
UniGeneHs.593422

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1T09X-ray2.70A/B1-414[»]
1T0LX-ray2.41A/B/C/D1-414[»]
ModBaseSearch...

Protein-protein interaction databases

IntActO75874. 1 interaction.

PTM databases

PhosphoSiteO75874.

2-D gel databases

OGPO75874.
REPRODUCTION-2DPAGEIPI00027223.

Proteomic databases

PeptideAtlasO75874.
PRIDEO75874.

Genome annotation databases

EnsemblENSG00000138413. Homo sapiens. [Contig view]
GeneID3417.
KEGGhsa:3417.
UCSCuc002vcs.1. human.

Organism-specific databases

GeneCardsGC02M208809.
H-InvDBHIX0002783.
HIX0033384.
HGNCHGNC:5382. IDH1.
MIM137800. phenotype.
147700. gene.
PharmGKBPA29630.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO75874.
HOVERGENO75874.
OMAO75874. AICIKGM.

Enzyme and pathway databases

BRENDA1.1.1.42. 247.
ReactomeREACT_16904. NADPH regeneration.
REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpressO75874.
BgeeO75874.
CleanExHS_IDH1.
GermOnlineENSG00000138413. Homo sapiens.

Family and domain databases

InterProIPR019818. IsoCit/isopropylmalate_DH_CS.
IPR001804. Isocitrate/isopropylmalate_DH.
IPR004790. Isocitrate_DH_NADP-dep_euk.
[Graphical view]
Gene3DG3DSA:3.40.718.10. IDH_IMDH. 1 hit.
PANTHERPTHR11822. IDH_NADP_euk. 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 Resources

NextBio13470.
SOURCESearch...

Entry information

Entry nameIDHC_HUMAN
AccessionPrimary (citable) accession number: O75874
Secondary accession number(s): Q93090, Q9NTJ9, Q9UKW8
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 11, 2002
Last modified: July 7, 2009
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents