P48735 · IDHP_HUMAN
- ProteinIsocitrate dehydrogenase [NADP], mitochondrial
- GeneIDH2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids452 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a role in intermediary metabolism and energy production (PubMed:19228619, PubMed:22416140).
It may tightly associate or interact with the pyruvate dehydrogenase complex (PubMed:19228619, PubMed:22416140).
It may tightly associate or interact with the pyruvate dehydrogenase complex (PubMed:19228619, PubMed:22416140).
Catalytic activity
- D-threo-isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Binds 1 Mg2+ or Mn2+ ion per subunit.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
3.1 μM | NADP | |||||
6 μM | isocitrate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
42.1 μmol/min/mg | for NADP | ||||
43.4 μmol/min/mg | for isocitrate |
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 115-117 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: TIT | ||||||
Binding site | 117 | D-threo-isocitrate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 122 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 134-140 | D-threo-isocitrate (UniProtKB | ChEBI) | ||||
Sequence: SPNGTIR | ||||||
Binding site | 149 | D-threo-isocitrate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 172 | D-threo-isocitrate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Site | 179 | Critical for catalysis | ||||
Sequence: Y | ||||||
Site | 251 | Critical for catalysis | ||||
Sequence: K | ||||||
Binding site | 291 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 299 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 314 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 349-354 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GTVTRH | ||||||
Binding site | 367 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: N |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Cellular Component | peroxisome | |
Molecular Function | isocitrate dehydrogenase (NADP+) activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | NAD binding | |
Biological Process | 2-oxoglutarate metabolic process | |
Biological Process | carbohydrate metabolic process | |
Biological Process | glyoxylate cycle | |
Biological Process | isocitrate metabolic process | |
Biological Process | NADP metabolic process | |
Biological Process | tricarboxylic acid cycle |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameIsocitrate dehydrogenase [NADP], mitochondrial
- EC number
- Short namesIDH
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP48735
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
D-2-hydroxyglutaric aciduria 2 (D2HGA2)
- Note
- DescriptionA neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine.
- See alsoMIM:613657
Natural variants in D2HGA2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_065174 | 140 | R>G | in D2HGA2; dbSNP:rs267606870 | |
VAR_065175 | 140 | R>Q | in D2HGA2; dbSNP:rs121913502 |
Glioma (GLM)
- Note
- DescriptionGliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.
- See alsoMIM:137800
Natural variants in GLM
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_073181 | 158 | P>L | in GLM; somatic mutation; dbSNP:rs2151549649 | |
VAR_073182 | 162 | P>S | in GLM; somatic mutation; dbSNP:rs1382680247 | |
VAR_073183 | 172 | R>G | in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs1057519906 | |
VAR_073184 | 172 | R>K | in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs121913503 | |
VAR_073185 | 172 | R>M | in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs121913503 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_065174 | 140 | in D2HGA2; dbSNP:rs267606870 | |||
Sequence: R → G | ||||||
Natural variant | VAR_065175 | 140 | in D2HGA2; dbSNP:rs121913502 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_073181 | 158 | in GLM; somatic mutation; dbSNP:rs2151549649 | |||
Sequence: P → L | ||||||
Natural variant | VAR_073182 | 162 | in GLM; somatic mutation; dbSNP:rs1382680247 | |||
Sequence: P → S | ||||||
Natural variant | VAR_073183 | 172 | in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs1057519906 | |||
Sequence: R → G | ||||||
Natural variant | VAR_073184 | 172 | in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs121913503 | |||
Sequence: R → K | ||||||
Natural variant | VAR_073185 | 172 | in GLM; somatic mutation; reduces enzymatic activity; dbSNP:rs121913503 | |||
Sequence: R → M | ||||||
Natural variant | VAR_076512 | 172 | found in patients with cartilagenous tumors; dbSNP:rs1057519736 | |||
Sequence: R → S | ||||||
Natural variant | VAR_076513 | 172 | found in patients with cartilagenous tumors; dbSNP:rs121913503 | |||
Sequence: R → T | ||||||
Natural variant | VAR_076514 | 172 | found in patients with cartilagenous tumors; dbSNP:rs1057519906 | |||
Sequence: R → W | ||||||
Mutagenesis | 413 | 44-fold loss in activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 413 | 20-fold decrease in Vmax. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 413 | No appreciable difference in Km for isocitrate and NADP. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 854 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-39 | UniProt | Mitochondrion | ||||
Sequence: MAGYLRVVRSLCRASGSRPAWAPAALTAPTSQEQPRRHY | |||||||
Chain | PRO_0000014420 | 40-452 | UniProt | Isocitrate dehydrogenase [NADP], mitochondrial | |||
Sequence: ADKRIKVAKPVVEMDGDEMTRIIWQFIKEKLILPHVDIQLKYFDLGLPNRDQTDDQVTIDSALATQKYSVAVKCATITPDEARVEEFKLKKMWKSPNGTIRNILGGTVFREPIICKNIPRLVPGWTKPITIGRHAHGDQYKATDFVADRAGTFKMVFTPKDGSGVKEWEVYNFPAGGVGMGMYNTDESISGFAHSCFQYAIQKKWPLYMSTKNTILKAYDGRFKDIFQEIFDKHYKTDFDKNKIWYEHRLIDDMVAQVLKSSGGFVWACKNYDGDVQSDILAQGFGSLGLMTSVLVCPDGKTIEAEAAHGTVTRHYREHQKGRPTSTNPIASIFAWTRGLEHRGKLDGNQDLIRFAQMLEKVCVETVESGAMTKDLAGCIHGLSNVKLNEHFLNTTDFLDTIKSNLDRALGRQ | |||||||
Modified residue | 45 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 48 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 67 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 69 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 80 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 80 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 106 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 106 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 155 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 166 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 166 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 180 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 180 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 193 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 193 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 199 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 256 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 256 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 263 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 272 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 275 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 280 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 282 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 282 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 301 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 341 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 350 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 352 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 384 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 384 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 400 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 413 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 423 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 442 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Acetylation at Lys-413 dramatically reduces catalytic activity. Deacetylated by SIRT3.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Structure
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
P48735-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length452
- Mass (Da)50,909
- Last updated2002-04-03 v2
- Checksum4DDC830AFC06AB52
P48735-2
- Name2
- Differences from canonical
- 1-52: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056278 | 1-52 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 34 | in Ref. 1; CAA49208 | ||||
Sequence: Q → H | ||||||
Sequence conflict | 435 | in Ref. 1; CAA49208 | ||||
Sequence: T → M |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X69433 EMBL· GenBank· DDBJ | CAA49208.1 EMBL· GenBank· DDBJ | mRNA | ||
AK294148 EMBL· GenBank· DDBJ | BAG57473.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312627 EMBL· GenBank· DDBJ | BAG35513.1 EMBL· GenBank· DDBJ | mRNA | ||
AK316388 EMBL· GenBank· DDBJ | BAH14759.1 EMBL· GenBank· DDBJ | mRNA | ||
AC087284 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC092769 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471101 EMBL· GenBank· DDBJ | EAX02082.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC009244 EMBL· GenBank· DDBJ | AAH09244.1 EMBL· GenBank· DDBJ | mRNA | ||
BC071828 EMBL· GenBank· DDBJ | AAH71828.1 EMBL· GenBank· DDBJ | mRNA |