Search results for IDH1

Showing 22 results out of 32

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (5 results from a total of 10)

Identifier: R-HSA-389546
Species: Homo sapiens
Compartment: peroxisomal matrix
Primary external reference: UniProt: IDH1: O75874
Identifier: R-HSA-389549
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: IDH1: O75874
Identifier: R-HSA-6800977
Species: Homo sapiens
Compartment: ficolin-1-rich granule lumen
Primary external reference: UniProt: IDH1: O75874
Identifier: R-HSA-6806433
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: IDH1: O75874
Identifier: R-HSA-6800980
Species: Homo sapiens
Compartment: secretory granule lumen
Primary external reference: UniProt: IDH1: O75874

Complex (5 results from a total of 7)

Identifier: R-HSA-389559
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-389557
Species: Homo sapiens
Compartment: peroxisomal matrix
Identifier: R-HSA-9761757
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-880029
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-880038
Species: Homo sapiens
Compartment: cytosol

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8958018
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENSG00000138413

Set (1 results from a total of 1)

Identifier: R-HSA-880004
Species: Homo sapiens
Compartment: cytosol

Reaction (5 results from a total of 7)

Identifier: R-HSA-9761822
Species: Homo sapiens
Compartment: nucleoplasm
IDH1 encodes the cytosolic NADP-dependent isocitrate dehydrogenase, which catalyzes the reversible conversion of isocitrate to 2-oxoglutarate, generating NADPH (reviewed in Mondesir et al, 2016). Through its role in generating NADPH as well as carbon intermediates of the citric acid cycle, IDH1 contributes to the maintenance of cellular redox balance and flux through metabolic pathways, including during oncogenesis (reviewed in Mondesir et al, 2016; Chang et al, 2019). IDH1 has been shown to be a direct target of NFE2L2, a key regulator of the antioxidant response pathway. NFE2L2 binds to the anti-oxidant response element (ARE) in the IDH1 promoter as assessed by ChIP-seq to promote NFE2L2-dependent expression (Mitsuishi et al, 2012; Thimmulappa et al, 2002; Wu et al, 2011; reviewed in Baird and Yamamoto, 2020; Hayes et al, 2020).
Identifier: R-HSA-9761844
Species: Homo sapiens
Compartment: nucleoplasm, cytosol
The IDH1 gene encodes the cytosolic NADP-dependent isocitrate dehydrogenase, which catalyzes the reversible conversion of isocitrate to 2-oxoglutarate, generating NADPH. IDH1 is thus a key player in maintaining the redox and metabolic balance in the cell and has been shown to be dysregulated in many cancers (reviewed in Mondesir et al, 2016; Chang et al, 2019). IDH1 expression is regulated downstream of the KEAP1-NFE2L2 pathway and has been shown to be a direct target of NFE2L2 (Mitsuishi et al, 2012; reviewed in Baird and Yamamoto, 2020; Hayes et al, 2020).
Identifier: R-HSA-880053
Species: Homo sapiens
Compartment: cytosol
Mutant forms of IDH1 in which the arginine residue at position 132 has been replaced by histidine, cystine, leucine, or serine catalyze the reaction of 2-oxoglutarate and NADPH + H+ to form (R)-2-hydroxyglutarate and NADP+. Like normal IDH1, the mutant enzyme forms a dimer located in the cytosol (Dang et al. 2009).

Such mutations occur frequently as a somatic event in human glioblastomas (Parsons et al. 2008). Cells expressing the mutant protein accumulate elevated levels of 2-hydroxyglutarate, probably in the cytosol as IDH1 is a cytosolic enzyme. The fate of the 2-hydroxyglutarate is unclear, but the high frequency with which the mutation is found in surveys of primary tumors is consistent with the possibility that it is advantageous to the tumor cells (Dang et al. 2009).

Identifier: R-HSA-389540
Species: Homo sapiens
Compartment: cytosol
Cytosolic IDH1 (isocitrate dehydrogenase 1) homodimer catalyzes the reaction of isocitrate and NADP+ to form 2-oxoglutarate, CO2, and NADPH + H+. The same enzyme can also localize to peroxisomes (Geisbrecht and Gould 1999; Xu et al. 2004). IDH1 doesn't seem to be part of a hypothetical cytosolic TCA cycle because its product 2-OG would have to be reimported into the mitochondrial matrix. However, the only known transporter of 2-OG, SLC25A12, mainly exports it in exchange with oxoadipate under normal physiological conditions (Fiermonte et al., 2001).
Identifier: R-HSA-389550
Species: Homo sapiens
Compartment: peroxisomal matrix
Peroxisomal IDH1 (isocitrate dehydrogenase 1) homodimer catalyzes the reaction of isocitrate and NADP+ to form 2-oxoglutarate, CO2, and NADPH + H+. The same enzyme can also localize to the cytosol in at least some cell types (Geisbrecht and Gould 1999; Xu et al. 2004).

Pathway (5 results from a total of 6)

Identifier: R-HSA-2978092
Species: Homo sapiens
Compartment: cytosol
Somatic mutations affecting arginine residue 132 of IDH1 (isocitrate dehydrogenase 1, a cytosolic enzyme that normally catalyzes the NADP+-dependent conversion of isocitrate to 2-oxoglutarate), are very commonly found in human glioblastomas (Parsons et al. 2008). These mutant proteins efficiently catalyze the NADPH-dependent reduction of 2-oxoglutarate to form 2-hydroxyglutarate. Cells expressing the mutant protein accumulate elevated levels of 2-hydroxyglutarate, probably in the cytosol as IDH1 is a cytosolic enzyme. The fate of the 2-hydroxyglutarate is unclear, but the high frequency with which the mutation is found in surveys of primary tumors is consistent with the possibility that it is advantageous to the tumor cells (Dang et al 2009).
Identifier: R-HSA-880009
Species: Homo sapiens
The two stereoisomers of 2-hydroxyglutarate are normally converted to 2-oxoglutarate in the mitochondrial matrix, and can then be metabolized by the citric acid cycle. The physiological sources of 2-hydroxyglutarate have not been established although plausible hypotheses are that it is generated by lysine breakdown or as a byproduct of delta-aminolevulinate metabolism. The stereoisomers are oxidized to 2-oxoglutarate in FAD-dependent reactions catalyzed by the enzymes D2HGDH (specific for R(-)-2-hydroxyglutarate) and L2HGDH (specific for S(-)-2-hydroxyglutarate). An inherited deficiency in either enzyme is associated with accumulation of 2-hydroxyglutarate and variable neurological symptoms. R(-)-2-hydroxyglutarate also reacts reversibly with succinate semialdehyde to form 4-hydroxybutyrate and 2-oxoglutarate, catalyzed by ADHFE1. No deficiencies of this enzyme have been found in patients with elevated 2-hydroxyglutarate levels (Struys 2006).
Identifier: R-HSA-9670621
Species: Homo sapiens
Compartment: nucleoplasm
ATRX (Alpha thalassemia mental retardation X-lined) and DAXX (Death domain-associated protein 6) chromatin remodeling factors form a complex that binds to subtelomeric regions and plays a role in inhibition of DNA recombination at telomere ends, probably by mediating loading of H3F3A histone at telomere ends and by repressing transcription of TERRA (Telomeric repeat containing RNA), a long noncoding telomeric repeats-containing RNA. Tumors positive for alternative lengthening of telomeres (ALT) markers often harbor loss-of-function mutations in ATRX, and more rarely in DAXX or missense mutations in H3F3A, implying that the impairment of function of one of these three proteins may contribute to initiation of the ALT process. Additionally, mutations in IDH, the tumor suppressor TP53 and SMARCAL1 are also observed in the context of ALT in certain types of human cancers, particularly sarcomas and tumors of the central nervous system (Jiao et al. 2012, Nicolle et al. 2019). For review, please refer to Gocha et al. 2013, Pickett and Reddel 2015, Amorim et al. 2016).
Identifier: R-HSA-9671555
Species: Homo sapiens
PDGFRA and PDGFRB are type III receptor tyrosine kinases that promote development and maintenance of mesenchymal tissues, including vascular smooth muscle, kidney, intestine, skin and lung, among others (reviewed in Tallquist and Kazlauskas, 2004; reviewed in Wang et al, 2016). Signaling through PDGF receptors stimulates cell proliferation and survival through activation of downstream signaling pathways including the RAS-MAP kinase cascade, PI3K signaling and STAT signaling (reviewed in Roskoski, 2018). Aberrant signaling through PDGF receptors is implicated in a number of human diseases. Point mutations in PDGFRA and, to a lesser extent, PDGFRB are implicated in a number of cancers, such as gastrointestinal stromal tumors (GIST; 5-10% mutation frequency in PDGFRA) and haematological cancers (Corless et al, 2005; Wang et al, 2016; reviewed in Klug et al, 2018). In addition, amplified signaling through the PDGF pathway can arise through gene fusion events or overexpression of ligand or receptor through gene amplification (Ozawa et al, 2010; Verhaak et al, 2010; reviewed in Appiah-Kubi et al, 2017).
Identifier: R-HSA-1268020
Species: Homo sapiens
Compartment: cytosol, mitochondrial inner membrane, mitochondrial intermembrane space, mitochondrial matrix, mitochondrial outer membrane
A human mitochondrion contains about 1500 proteins, more than 99% of which are encoded in the nucleus, synthesized in the cytosol and imported into the mitochondrion. Proteins are targeted to four locations (outer membrane, intermembrane space, inner membrane, and matrix) and must be sorted accordingly (reviewed in Kutik et al. 2007, Milenkovic et al. 2007, Bolender et al. 2008, Endo and Yamano 2009, Wiedemann and Pfanner 2017, Kang et al. 2018). Newly synthesized proteins are transported from the cytosol across the outer membrane by the TOMM40:TOMM70 complex. Proteins that contain presequences first interact with the TOMM20 subunit of the complex while proteins that contain internal targeting elements first interact with the TOMM70 subunit. After initial interaction the protein is conducted across the outer membrane by TOMM40 subunits. In yeast some proteins such as Aco1, Atp1, Cit1, Idh1, and Atp2 have both presequences that interact with TOM20 and mature regions that interact with TOM70 (Yamamoto et al. 2009).
After passage across the outer membrane, proteins may be targeted to the outer membrane via the SAMM50 complex, to the inner membrane via the TIMM22 or TIMM23 complexes (reviewed in van der Laan et al. 2010), to the matrix via the TIMM23 complex (reviewed in van der Laan et al. 2010), or proteins may fold and remain in the intermembrane space (reviewed in Stojanovski et al. 2008, Deponte and Hell 2009, Sideris and Tokatlidis 2010). Presequences on matrix and inner membrane proteins cause interaction with TIMM23 complexes; internal targeting sequences cause outer membrane proteins to interact with the SAMM50 complex and inner membrane proteins to interact with the TIMM22 complex. While in the intermembrane space hydrophobic proteins are chaperoned by the TIMM8:TIMM13 complex and/or the TIMM9:TIMM10:FXC1 complex.
Cite Us!