Reviewed, UniProtKB/Swiss-Prot O75874 (IDHC_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	414 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Glyoxylate bypass Tricarboxylic acid cycle
Cellular component	Cytoplasm Peroxisome
Coding sequence diversity	Polymorphism
Ligand	Magnesium Manganese Metal-binding NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	glyoxylate cycle Inferred from electronic annotation. Source: UniProtKB-KW isocitrate metabolic process Ref.1 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Ref.1 Traceable author statement. Source: ProtInc peroxisome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NAD or NADH binding Inferred from electronic annotation. Source: InterPro isocitrate dehydrogenase (NADP+) activity Ref.1 Traceable author statement. Source: ProtInc magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 414

414

Isocitrate dehydrogenase [NADP] cytoplasmic

PRO_0000083575

Regions

Nucleotide binding

75 – 77

3

NADP

Nucleotide binding

310 – 315

6

NADP

Region

94 – 100

7

Substrate binding

Sites

Metal binding

252

1

Magnesium or manganese

Metal binding

275

1

Magnesium or manganese

Binding site

77

1

Substrate

Binding site

82

1

NADP

Binding site

109

1

Substrate

Binding site

132

1

Substrate

Binding site

260

1

NADP

Binding site

328

1

NADP; via amide nitrogen and carbonyl oxygen

Site

139

1

Critical for catalysis

Site

212

1

Critical for catalysis

Natural variations

Natural variant

132

1

R → C in a colorectal cancer sample and GBM; somatic mutation.

VAR_036013

Natural variant

132

1

R → G in GBM; somatic mutation.

VAR_055454

Natural variant

132

1

R → H in GBM; somatic mutation.

VAR_055455

Natural variant

132

1

R → L in GBM; somatic mutation.

VAR_055456

Natural variant

132

1

R → S in GBM; somatic mutation.

VAR_055457

Natural variant

178

1

V → I: dbSNP rs34218846.

VAR_049780

Experimental info

Sequence conflict

32

1

F → I in CAB66637. Ref.3

Sequence conflict

126

1

K → E in CAB66637. Ref.3

Sequence conflict

218

1

K → I in AAD02918. Ref.1

Sequence conflict

329

1

P → L in AAD02918. Ref.1

Sequence conflict

381

1

K → R in AAD02918. Ref.1

Secondary structure

1

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414

Helix Strand Turn

Details...

Beta strand

5 – 14

10

Helix

17 – 29

13

Turn

30 – 34

5

Beta strand

35 – 43

9

Helix

46 – 51

6

Turn

52 – 54

3

Helix

55 – 67

13

Beta strand

68 – 72

5

Helix

80 – 86

7

Helix

95 – 103

9

Beta strand

106 – 111

6

Beta strand

128 – 133

6

Helix

137 – 140

4

Beta strand

142 – 146

5

Beta strand

148 – 158

11

Beta strand

165 – 172

8

Beta strand

177 – 185

9

Helix

186 – 203

18

Beta strand

207 – 211

5

Turn

213 – 215

3

Helix

219 – 234

16

Helix

236 – 241

6

Beta strand

246 – 250

5

Helix

251 – 260

10

Beta strand

265 – 269

5

Helix

271 – 285

15

Beta strand

290 – 296

7

Beta strand

303 – 306

4

Helix

313 – 320

8

Helix

330 – 347

18

Helix

350 – 368

19

Helix

374 – 380

7

Helix

383 – 385

3

Helix

388 – 390

3

Helix

394 – 411

18

Sequences

	Sequence		Length	Mass (Da)
	O75874-1 [UniParc]. Last modified July 11, 2002. Version 2. Checksum: 60428B0B6E5851DC	FASTA	414	46,659
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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

EMBLGenBankDDBJ

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.

IPI

IPI00027223.

PIR

T46280.

RefSeq

NP_005887.2.

UniGene

Hs.593422

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T09	X-ray	2.70	A/B	1-414	[»]
1T0L	X-ray	2.41	A/B/C/D	1-414	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O75874. 1 interaction.

PTM databases

PhosphoSite

O75874.

2-D gel databases

OGP

O75874.

REPRODUCTION-2DPAGE

IPI00027223.

Proteomic databases

PeptideAtlas

O75874.

PRIDE

O75874.

Genome annotation databases

Ensembl

ENSG00000138413. Homo sapiens. [Contig view]

GeneID

3417.

KEGG

hsa:3417.

UCSC

uc002vcs.1. human.

Organism-specific databases

GeneCards

GC02M208809.

H-InvDB

HIX0002783.
HIX0033384.

HGNC

HGNC:5382. IDH1.

MIM

137800. phenotype.
147700. gene.

PharmGKB

PA29630.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O75874.

HOVERGEN

O75874.

OMA

O75874. AICIKGM.

Enzyme and pathway databases

BRENDA

1.1.1.42. 247.

Reactome

REACT_16904. NADPH regeneration.
REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

O75874.

Bgee

O75874.

CleanEx

HS_IDH1.

GermOnline

ENSG00000138413. Homo sapiens.

Family and domain databases

InterPro

IPR019818. IsoCit/isopropylmalate_DH_CS.
IPR001804. Isocitrate/isopropylmalate_DH.
IPR004790. Isocitrate_DH_NADP-dep_euk.
[Graphical view]

Gene3D

G3DSA:3.40.718.10. IDH_IMDH. 1 hit.

PANTHER

PTHR11822. IDH_NADP_euk. 1 hit.

Pfam

PF00180. Iso_dh. 1 hit.
[Graphical view]

PIRSF

PIRSF000108. IDH_NADP. 1 hit.

TIGRFAMs

TIGR00127. nadp_idh_euk. 1 hit.

PROSITE

PS00470. IDH_IMDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

13470.

SOURCE

Search...

Entry information

Entry name

IDHC_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)