[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1021/bi00142a007; PubMed=1627563 [NCBI, ExPASy, EBI, Israel, Japan] Haselbeck R.J., Colman R.F., McAlister-Henn L.; "Isolation and sequence of a cDNA encoding porcine mitochondrial NADP-specific isocitrate dehydrogenase."; Biochemistry 31:6219-6223(1992).
[2]	PROTEIN SEQUENCE OF 82-91; 59-64; 201-211; 269-278 AND 369-392. TISSUE=Heart; PubMed=1869531 [NCBI, ExPASy, EBI, Israel, Japan] Smyth G.E., Colman R.F.; "Cysteinyl peptides of pig heart NADP-dependent isocitrate dehydrogenase that are modified upon inactivation by N-ethylmaleimide."; J. Biol. Chem. 266:14918-14925(1991).
[3]	PROTEIN SEQUENCE OF 383-395. PubMed=3624273 [NCBI, ExPASy, EBI, Israel, Japan] Ehrlich R.S., Colman R.F.; "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."; J. Biol. Chem. 262:12614-12619(1987).
[4]	ENZYME KINETICS, AND MUTAGENESIS OF TRY-148 AND LYS-220. DOI=10.1074/jbc.M303781200; PubMed=14512428 [NCBI, ExPASy, EBI, Israel, Japan] Kim T.K., Lee P., Colman R.F.; "Critical role of Lys212 and Tyr140 in porcine NADP-dependent isocitrate dehydrogenase."; J. Biol. Chem. 278:49323-49331(2003).
[5]	X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 9-421 IN COMPLEX WITH MANGANESE AND ISOCITRATE, AND SUBUNIT. DOI=10.1074/jbc.M207306200; PubMed=12207025 [NCBI, ExPASy, EBI, Israel, Japan] Ceccarelli C., Grodsky N.B., Ariyaratne N., Colman R.F., Bahnson B.J.; "Crystal structure of porcine mitochondrial NADP+-dependent isocitrate dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme mechanism."; J. Biol. Chem. 277:43454-43462(2002).

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.
CATALYTIC ACTIVITY: Oxalosuccinate + NADP⁺ = 2-oxoglutarate + CO₂ + NADPH.
COFACTOR: Binds 1 magnesium or manganese ion per subunit.
BIOPHYSICOCHEMICAL PROPERTIES:

Kinetic parameters: K_M=7.47 µM for isocitrate;
K_M=9.85 µM for NADP;
K_M=0.11 µM for manganese;
V_max=39.6 µmol/min/mg enzyme with isocitrate as substrate;
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Mitochondrion.
SIMILARITY: Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M86719; AAA31089.1; -; mRNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A43294; A43294.

UniGene

Ssc.2449

3D structure databases

PDB

1LWD; X-ray; 1.85 A; A/B=9-421.

[ExPASy / RCSB / EBI]

PDBsum

1LWD; -.

ModBase

P33198.

Ontologies

GO:0005739;	Cellular component: mitochondrion (inferred from electronic annotation from UniProtKB-KW).
GO:0004450;	Molecular function: isocitrate dehydrogenase (NADP+) activity (inferred from electronic annotation from InterPro).
GO:0000287;	Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0030145;	Molecular function: manganese ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0006097;	Biological process: glyoxylate cycle (inferred from electronic annotation from UniProtKB-KW).
GO:0006102;	Biological process: isocitrate metabolic process (inferred from electronic annotation from InterPro).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0006099;	Biological process: tricarboxylic acid cycle (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR004790; IsoCit_DHase_NADP-dep_euk.
IPR001804; IsoCit_IM_DHase.
Graphical view of domain structure.

Gene3D

G3DSA:3.40.718.10; IDH_IMDH; 1.

PANTHER

PTHR11822; IDH_NADP_euk; 1.

Pfam

PF00180; Iso_dh; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000108; IDH_NADP; 1.

TIGRFAMs

TIGR00127; nadp_idh_euk; 1.

PROSITE

PS00470; IDH_IMDH; 1.

ProtoNet

P33198.

Phylogenomic databases

HOVERGEN

P33198; -.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Acetylation; Direct protein sequencing; Glyoxylate bypass; Magnesium; Manganese; Metal-binding; Mitochondrion; NADP; Oxidoreductase; Transit peptide; Tricarboxylic acid cycle.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`TRANSIT`	`<1 8`	`>8`	`Mitochondrion.`
`CHAIN`	`9 421`	`413`	`Isocitrate dehydrogenase [NADP], mitochondrial.`	`PRO_0000014422`
`NP_BIND`	`84 86`	`3`	`NADP (By similarity).`
`NP_BIND`	`318 323`	`6`	`NADP (By similarity).`
`REGION`	`103 109`	`7`	`Substrate binding.`
`METAL`	`260 260`		`Magnesium or manganese.`
`METAL`	`283 283`		`Magnesium or manganese.`
`BINDING`	`86 86`		`Substrate.`
`BINDING`	`91 91`		`NADP (By similarity).`
`BINDING`	`118 118`		`Substrate.`
`BINDING`	`141 141`		`Substrate.`
`BINDING`	`268 268`		`NADP (By similarity).`
`BINDING`	`336 336`		`NADP; via amide nitrogen and carbonyl oxygen.`
`SITE`	`148 148`	`1`	`Critical for catalysis.`
`SITE`	`220 220`	`1`	`Critical for catalysis.`
`MOD_RES`	`75 75`		`N6-acetyllysine (By similarity).`
`MOD_RES`	`241 241`		`N6-acetyllysine (By similarity).`
`MUTAGEN`	`148 148`		`Y->F: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP.`
`MUTAGEN`	`220 220`		`K->Q,Y: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP.`
`NON_TER`	`1 1`
`STRAND`	`19 23`	`5`
`HELIX`	`26 38`	`13`
`TURN`	`39 43`	`5`
`STRAND`	`48 52`	`5`
`HELIX`	`55 60`	`6`
`TURN`	`61 63`	`3`
`HELIX`	`64 76`	`13`
`STRAND`	`77 81`	`5`
`HELIX`	`89 95`	`7`
`HELIX`	`104 112`	`9`
`STRAND`	`114 120`	`7`
`STRAND`	`137 142`	`6`
`HELIX`	`146 149`	`4`
`STRAND`	`151 155`	`5`
`STRAND`	`157 167`	`11`
`STRAND`	`174 183`	`10`
`STRAND`	`185 193`	`9`
`HELIX`	`194 211`	`18`
`STRAND`	`215 219`	`5`
`TURN`	`221 223`	`3`
`HELIX`	`227 242`	`16`
`HELIX`	`244 249`	`6`
`STRAND`	`254 258`	`5`
`HELIX`	`259 268`	`10`
`STRAND`	`273 277`	`5`
`HELIX`	`279 293`	`15`
`STRAND`	`298 304`	`7`
`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`

Sequence information

Length: 421 AA [This is the length of the partial sequence of the unprocessed precursor]

Molecular weight: 47526 Da [This is the MW of the partial sequence of the unprocessed precursor]

CRC64: 14862D47C00A053F [This is a checksum on the sequence]

        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

P33198 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools