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P33198 (IDHP_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length421 AA.
Sequence statusFragment.
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.

Subunit structure

Homodimer. Ref.5

Subcellular location

Mitochondrion.

Post-translational modification

Acetylation at Lys-382 dramatically reduces catalytic activity. Deacetylated by SIRT3 By similarity.

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide‹1 – 8›8Mitochondrion
Chain9 – 421413Isocitrate dehydrogenase [NADP], mitochondrial
PRO_0000014422

Regions

Nucleotide binding84 – 863NADP By similarity
Nucleotide binding318 – 3236NADP By similarity
Region103 – 1097Substrate binding

Sites

Metal binding2601Magnesium or manganese
Metal binding2831Magnesium or manganese
Binding site861Substrate
Binding site911NADP By similarity
Binding site1181Substrate
Binding site1411Substrate
Binding site2681NADP By similarity
Binding site3361NADP; via amide nitrogen and carbonyl oxygen
Site1481Critical for catalysis
Site2201Critical for catalysis

Amino acid modifications

Modified residue141N6-acetyllysine By similarity
Modified residue171N6-acetyllysine By similarity
Modified residue361N6-acetyllysine By similarity
Modified residue381N6-acetyllysine By similarity
Modified residue491N6-acetyllysine; alternate By similarity
Modified residue491N6-succinyllysine; alternate By similarity
Modified residue751N6-acetyllysine; alternate By similarity
Modified residue751N6-succinyllysine; alternate By similarity
Modified residue1241N6-acetyllysine By similarity
Modified residue1351N6-acetyllysine; alternate By similarity
Modified residue1351N6-succinyllysine; alternate By similarity
Modified residue1491N6-acetyllysine; alternate By similarity
Modified residue1491N6-succinyllysine; alternate By similarity
Modified residue1621N6-acetyllysine; alternate By similarity
Modified residue1621N6-succinyllysine; alternate By similarity
Modified residue1681N6-acetyllysine By similarity
Modified residue2251N6-acetyllysine; alternate By similarity
Modified residue2251N6-succinyllysine; alternate By similarity
Modified residue2321N6-acetyllysine By similarity
Modified residue2411N6-acetyllysine By similarity
Modified residue2441N6-acetyllysine By similarity
Modified residue2491N6-acetyllysine By similarity
Modified residue2511N6-acetyllysine; alternate By similarity
Modified residue2511N6-succinyllysine; alternate By similarity
Modified residue3531N6-acetyllysine; alternate By similarity
Modified residue3531N6-succinyllysine; alternate By similarity
Modified residue3691N6-acetyllysine By similarity
Modified residue3821N6-acetyllysine By similarity
Modified residue4111N6-acetyllysine By similarity

Experimental info

Mutagenesis1481Y → F: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP. Ref.4
Mutagenesis2201K → Q or Y: Large decrease in Vmax and insignificant change in KM for isocitrate and NADP. Ref.4
Non-terminal residue11

Secondary structure

............................................................... 421
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P33198 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 14862D47C00A053F

FASTA42147,526
        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 

« Hide

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.
PIRA43294.
UniGeneSsc.58398.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LWDX-ray1.85A/B9-421[»]
ProteinModelPortalP33198.
SMRP33198. Positions 9-421.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9823.ENSSSCP00000002027.

Proteomic databases

PaxDbP33198.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGCOG0538.
HOGENOMHOG000019858.
HOVERGENHBG006119.

Enzyme and pathway databases

SABIO-RKP33198.

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

EvolutionaryTraceP33198.

Entry information

Entry nameIDHP_PIG
AccessionPrimary (citable) accession number: P33198
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references