P33198 (IDHP_PIG) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Sus scrofa (Pig) [Reference proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	421 AA.
Sequence status	Fragment.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Subunit structure	Homodimer. Ref.5
Subcellular location	Mitochondrion.
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.
Biophysicochemical properties	Kinetic parameters: KM=7.47 µM for isocitrate Ref.4 KM=9.85 µM for NADP KM=0.11 µM for manganese Vmax=39.6 µmol/min/mg enzyme with isocitrate as substrate

Ontologies

Keywords
Biological process	Glyoxylate bypass Tricarboxylic acid cycle
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	Magnesium Manganese Metal-binding NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	2-oxoglutarate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glyoxylate cycle Inferred from electronic annotation. Source: UniProtKB-KW isocitrate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara
Molecular_function	NAD binding Inferred from electronic annotation. Source: InterPro isocitrate dehydrogenase (NADP+) activity Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

‹1 – 8

›8

Mitochondrion

Chain

9 – 421

413

Isocitrate dehydrogenase [NADP], mitochondrial

PRO_0000014422

Regions

Nucleotide binding

84 – 86

3

NADP By similarity

Nucleotide binding

318 – 323

6

NADP By similarity

Region

103 – 109

7

Substrate binding

Sites

Metal binding

260

1

Magnesium or manganese

Metal binding

283

1

Magnesium or manganese

Binding site

86

1

Substrate

Binding site

91

1

NADP By similarity

Binding site

118

1

Substrate

Binding site

141

1

Substrate

Binding site

268

1

NADP By similarity

Binding site

336

1

NADP; via amide nitrogen and carbonyl oxygen

Site

148

1

Critical for catalysis

Site

220

1

Critical for catalysis

Amino acid modifications

Modified residue

36

1

N6-acetyllysine By similarity

Modified residue

75

1

N6-acetyllysine By similarity

Modified residue

124

1

N6-acetyllysine By similarity

Modified residue

135

1

N6-acetyllysine By similarity

Modified residue

149

1

N6-acetyllysine By similarity

Modified residue

225

1

N6-acetyllysine By similarity

Modified residue

232

1

N6-acetyllysine By similarity

Modified residue

241

1

N6-acetyllysine By similarity

Modified residue

244

1

N6-acetyllysine By similarity

Modified residue

251

1

N6-acetyllysine By similarity

Modified residue

411

1

N6-acetyllysine By similarity

Experimental info

Mutagenesis

148

1

Y → F: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP. Ref.4

Mutagenesis

220

1

K → Q or Y: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP. Ref.4

Non-terminal residue

1

1

Secondary structure

1

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421

Helix Strand Turn

Details...

Beta strand

19 – 23

5

Helix

26 – 38

13

Turn

39 – 43

5

Beta strand

48 – 52

5

Helix

55 – 60

6

Turn

61 – 63

3

Helix

64 – 76

13

Beta strand

77 – 81

5

Helix

89 – 95

7

Helix

104 – 112

9

Beta strand

114 – 120

7

Beta strand

137 – 142

6

Helix

146 – 149

4

Beta strand

151 – 155

5

Beta strand

157 – 167

11

Beta strand

174 – 183

10

Beta strand

185 – 193

9

Helix

194 – 211

18

Beta strand

215 – 219

5

Turn

221 – 223

3

Helix

227 – 242

16

Helix

244 – 249

6

Beta strand

254 – 258

5

Helix

259 – 268

10

Beta strand

273 – 277

5

Helix

279 – 293

15

Beta strand

298 – 304

7

Beta strand

311 – 314

4

Helix

321 – 328

8

Helix

338 – 355

18

Helix

358 – 376

19

Helix

382 – 389

8

Turn

396 – 398

3

Helix

403 – 419

17

Sequences

	Sequence		Length	Mass (Da)
	P33198 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 14862D47C00A053F	FASTA	421	47,526
	10 20 30 40 50 60 ARAAARHYAD QRIKVAKPVV EMDGDEMTRI IWQFIKEKLI LPHVDVQLKY FDLGLPNRDQ 70 80 90 100 110 120 TNDQVTIDSA LATQKYSVAV KCATITPDEA RVEEFKLKKM WKSPNGTIRN ILGGTVFREP 130 140 150 160 170 180 IICKNIPRLV PGWTKPITIG RHAHGDQYKA TDFVVDRAGT FKIVFTPKDG SSAKQWEVYN 190 200 210 220 230 240 FPAGGVGMGM YNTDESISGF AHSCFQYAIQ KKWPLYMSTK NTILKAYDGR FKDIFQEIFE 250 260 270 280 290 300 KHYKTDFDKY KIWYEHRLID DMVAQVLKSS GGFVWACKNY DGDVQSDILA QGFGSLGLMT 310 320 330 340 350 360 SVLVCPDGKT IEAEAAHGTV TRHYREHQKG RPTSTNPIAS IFAWTRGLEH RGKLDGNQDL 370 380 390 400 410 420 IRFAQTLEKV CVETVESGAM TKDLAGCIHG LSNVKLNEHF LNTSDFLDTI KSNLDRALGR Q

References

[1]	"Isolation and sequence of a cDNA encoding porcine mitochondrial NADP-specific isocitrate dehydrogenase." Haselbeck R.J., Colman R.F., McAlister-Henn L. Biochemistry 31:6219-6223(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cysteinyl peptides of pig heart NADP-dependent isocitrate dehydrogenase that are modified upon inactivation by N-ethylmaleimide." Smyth G.E., Colman R.F. J. Biol. Chem. 266:14918-14925(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 82-91; 59-64; 201-211; 269-278 AND 369-392. Tissue: Heart.
[3]	"Characterization of an active site peptide modified by the substrate analogue 3-bromo-2-ketoglutarate on a single chain of dimeric NADP+-dependent isocitrate dehydrogenase." Ehrlich R.S., Colman R.F. J. Biol. Chem. 262:12614-12619(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 383-395.
[4]	"Critical role of Lys212 and Tyr140 in porcine NADP-dependent isocitrate dehydrogenase." Kim T.K., Lee P., Colman R.F. J. Biol. Chem. 278:49323-49331(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME KINETICS, MUTAGENESIS OF TRY-148 AND LYS-220.
[5]	"Crystal structure of porcine mitochondrial NADP+-dependent isocitrate dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme mechanism." Ceccarelli C., Grodsky N.B., Ariyaratne N., Colman R.F., Bahnson B.J. J. Biol. Chem. 277:43454-43462(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 9-421 IN COMPLEX WITH MANGANESE AND ISOCITRATE, SUBUNIT.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M86719 mRNA. Translation: AAA31089.1.

PIR

A43294.

UniGene

Ssc.58398.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LWD	X-ray	1.85	A/B	9-421	[»]

ProteinModelPortal

P33198.

SMR

P33198. Positions 9-421.

ModBase

Search...

Protein-protein interaction databases

STRING

9823.ENSSSCP00000002027.

Proteomic databases

PaxDb

P33198.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Phylogenomic databases

eggNOG

COG0538.

HOGENOM

HOG000019858.

HOVERGEN

HBG006119.

OrthoDB

EOG42V8G4.

Enzyme and pathway databases

SABIO-RK

P33198.

Gene expression databases

ArrayExpress

P33198.

Family and domain databases

Gene3D

3.40.718.10. 1 hit.

InterPro

IPR019818. IsoCit/isopropylmalate_DH_CS.
IPR004790. Isocitrate_DH_NADP.
IPR024084. IsoPropMal-DH-like_dom.
[Graphical view]

PANTHER

PTHR11822. PTHR11822. 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

EvolutionaryTrace

P33198.

Entry information

Entry name

IDHP_PIG

Accession

Primary (citable) accession number: P33198

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	April 3, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program